Osteoporosis

People who maintain a vegan diet show significant deficits in bone microarchitecture, compared with omnivores; however, resistance training not only appears to improve those deficits but may have a stronger effect in vegans, suggesting an important strategy in maintaining bone health with a vegan diet.

“We expected better bone structure in both vegans and omnivores who reported resistance training,” first author Robert Wakolbinger-Habel, MD, PhD, of St. Vincent Hospital Vienna and the Medical University of Vienna, said in an interview.

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“However, we expected [there would still be] differences in structure between vegans and omnivores [who practiced resistance training], as previous literature reported higher fracture rates in vegans,” he said. “Still, the positive message is that ‘pumping iron’ could counterbalance these differences between vegans and omnivores.”

The research was published online in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
 

Exercise significantly impacts bone health in vegans

The potential effects of the plant-based vegan diet on bone health have been reported in studies linking the diet to an increased risk of fractures and lower bone mineral density (BMD), with common theories including lower bone- and muscle-building protein in vegan diets.

However, most previous studies have not considered other key factors, such as the effects of exercise, the authors noted.

“While previous studies on bone health in vegans only took BMD, biochemical and nutritional parameters into account, they did not consider the significant effects of physical activity,” they wrote.

“By ignoring these effects, important factors influencing bone health are neglected.”

For the study, 88 participants were enrolled in Vienna, with vegan participants recruited with the help of the Austrian Vegan Society.

Importantly, the study documented participants’ bone microarchitecture, a key measure of bone strength that has also not been previously investigated in vegans, using high-resolution peripheral quantitative CT.

Inclusion criteria included maintaining an omnivore diet of meat and plant-based foods or a vegan diet for at least 5 years, not being underweight or obese (body mass index [BMI], 18.5-30 kg/m²), being age 30-50 years, and being premenopausal.

Of the participants, 43 were vegan and 45 were omnivores, with generally equal ratios of men and women.

Vegan bone deficits disappear with strength training

Overall, compared with omnivores, the vegan group showed significant deficits in 7 of 14 measures of BMI-adjusted trabecular and cortical structure (all P < .05).

Among participants who reported no resistance training, vegans still showed significant decreases in bone microarchitecture, compared with omnivores, including radius trabecular BMD, radius trabecular bone volume fraction, and other tibial and cortical bone microarchitecture measures.

However, among those who did report progressive resistant training (20 vegans and 25 omnivores), defined as using machines, free weights, or bodyweight resistance exercises at least once a week, those differences disappeared and there were no significant differences in BMI-adjusted bone microarchitecture between vegans and omnivores after the 5 years.

Of note, no significant differences in bone microarchitecture were observed between those who performed exclusively aerobic activities and those who reported no sports activities in the vegan or omnivore group.

Based on the findings, “other types of exercise such as aerobics, cycling, etc, would not be sufficient for a similar positive effect on bone [as resistance training],” Dr. Wakolbinger-Habel said.

Although the findings suggest that resistance training seemed to allow vegans to “catch up” with omnivores in terms of bone microarchitecture, Dr. Wakolbinger-Habel cautioned that a study limitation is the relatively low number of participants.

“The absolute numbers suggest that in vegans the differences, and the relative effect, respectively of resistance training might be larger,” he said. “However, the number of participants in the subgroups is small and it is still an observational study, so we need to be careful in drawing causal conclusions.”

Serum bone markers were within normal ranges across all subgroups. And although there were some correlations between nutrient intake and bone microarchitecture among vegans who did and did not practice resistance training, no conclusions could be drawn from that data, the authors noted.

“Based on our data, the structural [differences between vegans and omnivores] cannot solely be explained by deficits in certain nutrients according to lifestyle,” the authors concluded.
 

Mechanisms

The mechanisms by which progressive resistance training could result in the benefits include that mechanical loads trigger stimulation of key pathways involved in bone formation, or mechanotransduction, the authors explained.

The unique effects have been observed in other studies, including one study showing that, among young adult runners, the addition of resistance training once a week was associated with significantly greater BMD.

“Veganism is a global trend with strongly increasing numbers of people worldwide adhering to a purely plant-based diet,” first author Christian Muschitz, MD, also of St. Vincent Hospital Vienna and the Medical University of Vienna, said in a press statement.

“Our study showed resistance training offsets diminished bone structure in vegan people when compared to omnivores,” he said.

Dr. Wakolbinger-Habel recommended that, based on the findings, “exercise, including resistance training, should be strongly advocated [for vegans], I would say, at least two times per week.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who maintain a vegan diet show significant deficits in bone microarchitecture, compared with omnivores; however, resistance training not only appears to improve those deficits but may have a stronger effect in vegans, suggesting an important strategy in maintaining bone health with a vegan diet.

“We expected better bone structure in both vegans and omnivores who reported resistance training,” first author Robert Wakolbinger-Habel, MD, PhD, of St. Vincent Hospital Vienna and the Medical University of Vienna, said in an interview.

Thinkstock.com

“However, we expected [there would still be] differences in structure between vegans and omnivores [who practiced resistance training], as previous literature reported higher fracture rates in vegans,” he said. “Still, the positive message is that ‘pumping iron’ could counterbalance these differences between vegans and omnivores.”

The research was published online in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
 

Exercise significantly impacts bone health in vegans

The potential effects of the plant-based vegan diet on bone health have been reported in studies linking the diet to an increased risk of fractures and lower bone mineral density (BMD), with common theories including lower bone- and muscle-building protein in vegan diets.

However, most previous studies have not considered other key factors, such as the effects of exercise, the authors noted.

“While previous studies on bone health in vegans only took BMD, biochemical and nutritional parameters into account, they did not consider the significant effects of physical activity,” they wrote.

“By ignoring these effects, important factors influencing bone health are neglected.”

For the study, 88 participants were enrolled in Vienna, with vegan participants recruited with the help of the Austrian Vegan Society.

Importantly, the study documented participants’ bone microarchitecture, a key measure of bone strength that has also not been previously investigated in vegans, using high-resolution peripheral quantitative CT.

Inclusion criteria included maintaining an omnivore diet of meat and plant-based foods or a vegan diet for at least 5 years, not being underweight or obese (body mass index [BMI], 18.5-30 kg/m²), being age 30-50 years, and being premenopausal.

Of the participants, 43 were vegan and 45 were omnivores, with generally equal ratios of men and women.

Vegan bone deficits disappear with strength training

Overall, compared with omnivores, the vegan group showed significant deficits in 7 of 14 measures of BMI-adjusted trabecular and cortical structure (all P < .05).

Among participants who reported no resistance training, vegans still showed significant decreases in bone microarchitecture, compared with omnivores, including radius trabecular BMD, radius trabecular bone volume fraction, and other tibial and cortical bone microarchitecture measures.

However, among those who did report progressive resistant training (20 vegans and 25 omnivores), defined as using machines, free weights, or bodyweight resistance exercises at least once a week, those differences disappeared and there were no significant differences in BMI-adjusted bone microarchitecture between vegans and omnivores after the 5 years.

Of note, no significant differences in bone microarchitecture were observed between those who performed exclusively aerobic activities and those who reported no sports activities in the vegan or omnivore group.

Based on the findings, “other types of exercise such as aerobics, cycling, etc, would not be sufficient for a similar positive effect on bone [as resistance training],” Dr. Wakolbinger-Habel said.

Although the findings suggest that resistance training seemed to allow vegans to “catch up” with omnivores in terms of bone microarchitecture, Dr. Wakolbinger-Habel cautioned that a study limitation is the relatively low number of participants.

“The absolute numbers suggest that in vegans the differences, and the relative effect, respectively of resistance training might be larger,” he said. “However, the number of participants in the subgroups is small and it is still an observational study, so we need to be careful in drawing causal conclusions.”

Serum bone markers were within normal ranges across all subgroups. And although there were some correlations between nutrient intake and bone microarchitecture among vegans who did and did not practice resistance training, no conclusions could be drawn from that data, the authors noted.

“Based on our data, the structural [differences between vegans and omnivores] cannot solely be explained by deficits in certain nutrients according to lifestyle,” the authors concluded.
 

Mechanisms

The mechanisms by which progressive resistance training could result in the benefits include that mechanical loads trigger stimulation of key pathways involved in bone formation, or mechanotransduction, the authors explained.

The unique effects have been observed in other studies, including one study showing that, among young adult runners, the addition of resistance training once a week was associated with significantly greater BMD.

“Veganism is a global trend with strongly increasing numbers of people worldwide adhering to a purely plant-based diet,” first author Christian Muschitz, MD, also of St. Vincent Hospital Vienna and the Medical University of Vienna, said in a press statement.

“Our study showed resistance training offsets diminished bone structure in vegan people when compared to omnivores,” he said.

Dr. Wakolbinger-Habel recommended that, based on the findings, “exercise, including resistance training, should be strongly advocated [for vegans], I would say, at least two times per week.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who maintain a vegan diet show significant deficits in bone microarchitecture, compared with omnivores; however, resistance training not only appears to improve those deficits but may have a stronger effect in vegans, suggesting an important strategy in maintaining bone health with a vegan diet.

“We expected better bone structure in both vegans and omnivores who reported resistance training,” first author Robert Wakolbinger-Habel, MD, PhD, of St. Vincent Hospital Vienna and the Medical University of Vienna, said in an interview.

Thinkstock.com

“However, we expected [there would still be] differences in structure between vegans and omnivores [who practiced resistance training], as previous literature reported higher fracture rates in vegans,” he said. “Still, the positive message is that ‘pumping iron’ could counterbalance these differences between vegans and omnivores.”

The research was published online in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
 

Exercise significantly impacts bone health in vegans

The potential effects of the plant-based vegan diet on bone health have been reported in studies linking the diet to an increased risk of fractures and lower bone mineral density (BMD), with common theories including lower bone- and muscle-building protein in vegan diets.

However, most previous studies have not considered other key factors, such as the effects of exercise, the authors noted.

“While previous studies on bone health in vegans only took BMD, biochemical and nutritional parameters into account, they did not consider the significant effects of physical activity,” they wrote.

“By ignoring these effects, important factors influencing bone health are neglected.”

For the study, 88 participants were enrolled in Vienna, with vegan participants recruited with the help of the Austrian Vegan Society.

Importantly, the study documented participants’ bone microarchitecture, a key measure of bone strength that has also not been previously investigated in vegans, using high-resolution peripheral quantitative CT.

Inclusion criteria included maintaining an omnivore diet of meat and plant-based foods or a vegan diet for at least 5 years, not being underweight or obese (body mass index [BMI], 18.5-30 kg/m²), being age 30-50 years, and being premenopausal.

Of the participants, 43 were vegan and 45 were omnivores, with generally equal ratios of men and women.

Vegan bone deficits disappear with strength training

Overall, compared with omnivores, the vegan group showed significant deficits in 7 of 14 measures of BMI-adjusted trabecular and cortical structure (all P < .05).

Among participants who reported no resistance training, vegans still showed significant decreases in bone microarchitecture, compared with omnivores, including radius trabecular BMD, radius trabecular bone volume fraction, and other tibial and cortical bone microarchitecture measures.

However, among those who did report progressive resistant training (20 vegans and 25 omnivores), defined as using machines, free weights, or bodyweight resistance exercises at least once a week, those differences disappeared and there were no significant differences in BMI-adjusted bone microarchitecture between vegans and omnivores after the 5 years.

Of note, no significant differences in bone microarchitecture were observed between those who performed exclusively aerobic activities and those who reported no sports activities in the vegan or omnivore group.

Based on the findings, “other types of exercise such as aerobics, cycling, etc, would not be sufficient for a similar positive effect on bone [as resistance training],” Dr. Wakolbinger-Habel said.

Although the findings suggest that resistance training seemed to allow vegans to “catch up” with omnivores in terms of bone microarchitecture, Dr. Wakolbinger-Habel cautioned that a study limitation is the relatively low number of participants.

“The absolute numbers suggest that in vegans the differences, and the relative effect, respectively of resistance training might be larger,” he said. “However, the number of participants in the subgroups is small and it is still an observational study, so we need to be careful in drawing causal conclusions.”

Serum bone markers were within normal ranges across all subgroups. And although there were some correlations between nutrient intake and bone microarchitecture among vegans who did and did not practice resistance training, no conclusions could be drawn from that data, the authors noted.

“Based on our data, the structural [differences between vegans and omnivores] cannot solely be explained by deficits in certain nutrients according to lifestyle,” the authors concluded.
 

Mechanisms

The mechanisms by which progressive resistance training could result in the benefits include that mechanical loads trigger stimulation of key pathways involved in bone formation, or mechanotransduction, the authors explained.

The unique effects have been observed in other studies, including one study showing that, among young adult runners, the addition of resistance training once a week was associated with significantly greater BMD.

“Veganism is a global trend with strongly increasing numbers of people worldwide adhering to a purely plant-based diet,” first author Christian Muschitz, MD, also of St. Vincent Hospital Vienna and the Medical University of Vienna, said in a press statement.

“Our study showed resistance training offsets diminished bone structure in vegan people when compared to omnivores,” he said.

Dr. Wakolbinger-Habel recommended that, based on the findings, “exercise, including resistance training, should be strongly advocated [for vegans], I would say, at least two times per week.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.

Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.

“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”

But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing risks

The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.

Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.

In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.

Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.

Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.

The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.

Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.

Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.

“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.

Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.

“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
 

Promoting bone health

Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.

The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).

Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.

In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.

“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.

Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.

“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.

“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.

The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.

Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.

“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”

But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing risks

The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.

Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.

In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.

Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.

Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.

The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.

Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.

Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.

“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.

Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.

“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
 

Promoting bone health

Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.

The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).

Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.

In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.

“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.

Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.

“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.

“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.

The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Patients with alcohol-related cirrhosis have a higher fracture rate and a higher post-fracture mortality rate, compared with the general population, according to a large new study from Sweden.

Alcohol-related cirrhosis was associated with an almost fourfold increased fracture rate, and the post-fracture mortality rates were higher at both 30 days and 1 year later.

“Half of all fractures were presumably associated with osteoporosis,” write the study authors, who are gastroenterologists and epidemiologists at the Karolinska Institute, Stockholm. “This suggests that existing pharmacotherapy for osteoporosis may reduce the fracture risk in patients with alcohol-related cirrhosis and possibly also reduce mortality rates.”

But, the authors continue, “our data indicate that osteoporosis may not be the only explanatory factor for this increased fracture risk. Removing modifiable risk factors such as smoking, heavy alcohol use, or malnutrition may further reduce the risk of fractures.”

The study was published online in Clinical Gastroenterology and Hepatology.
 

Analyzing risks

The association between liver cirrhosis and fractures appears strongest in patients with alcohol-related cirrhosis, the most common cause of cirrhosis in many countries, including Sweden, the authors write.

Previous studies have examined mostly relative risk or hip fractures. The authors aimed to determine not only the relative risk but also the absolute risk, which “can better inform clinicians and policymakers of the actual size of the problem,” they write.

In a nationwide population-based cohort study, they analyzed data from the Swedish National Patient Registry between 1969 and 2016, which included 25,090 patients with alcohol-related cirrhosis. Patients were matched for sex, age, and municipality with 239,458 controls from the Swedish Total Population Registry. They calculated the cumulative incidence of fractures and accounted for competing risks, such as death or liver transportation.

Overall, 48,635 fractures occurred during 3.4 million person-years of follow-up, including 3,659 (14.6%) among patients and 44,976 (18.8%) among controls.

Patients with alcohol-related cirrhosis had a 3.8-times higher fracture rate, with 38.7 fractures per 1,000 person-years, compared with 13.3 in controls. Alcohol-related cirrhosis was also associated with a 1.9-times higher fracture rate than nonalcoholic cirrhosis and a 1.3-times higher fracture rate than noncirrhotic alcohol-related liver disease.

The cumulative incidence of fractures was elevated for patients with alcohol-related cirrhosis in the first 19 years of follow-up, with a 5-year risk at nearly 10%, compared with 4.5% for controls, and a 10-year risk of 13.5%, compared with 8.7% for controls.

Among those with a fracture, the median time to death was 2.8 years in patients with alcohol-related cirrhosis and 3.5 years in controls.

Patients with alcohol-related cirrhosis had a 1.6-times higher post-fracture mortality rate at 30 days, as well as a 1.8-times higher post-fracture mortality rate after one year.

“Falls and fractures kill patients with cirrhosis. Data like these are crucial to spread awareness and represent a call to arms,” Elliot Tapper, MD, an assistant professor of gastroenterology at the University of Michigan, Ann Arbor, told this news organization.

Dr. Tapper, who wasn’t involved with this study, researches the health outcomes of patients with cirrhosis. His previous studies have found that falls, injuries, and death are common in patients with cirrhosis, which could be predicted with an algorithm based on a prior history of falls, blood sodium level, mobility, and quality of life.

“The data emphasize that a fall and fracture herald a time of increased risk,” he said. “Research is needed to develop interventions that prevent falls and help patients remain more resilient when they happen.”
 

Promoting bone health

Osteoporosis was the most common presumed mechanism in both patients with alcohol-related cirrhosis (49.4%) and controls (52.2%), while high-energy trauma from motor vehicle crashes or heights preceded 10.9% of fractures in patients and 13.5% in controls.

The Karolinska Institute study found that patients with alcohol-related cirrhosis had a 4.4-times higher rate of osteoporotic fracture than controls, which remained 3.6-times higher when using a stricter definition of osteoporotic fracture (a diagnosis of osteoporosis before, at, or within 3 months from the date of a fracture of the vertebrae, pelvis, proximal humerus, distal forearm, or hip).

Patients with osteoporosis at baseline had a 2.5-times higher incidence of fractures than controls with baseline osteoporosis. The absolute risk of fractures in patients with alcohol-related cirrhosis and osteoporosis was higher than for controls with osteoporosis during the first 3 years after a cirrhosis diagnosis.

In addition, the post-fracture mortality rate in those with osteoporosis was more than double in patients with cirrhosis in the first 30 days after a fracture and more than tripled after one year.

“Bone health isn’t necessarily prioritized for our patients, even though it is linked to higher mortality and disability,” Arpan Patel, MD, PhD, a hepatologist at the West Los Angeles VA Medical Center and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, told this news organization.

Dr. Patel, who wasn’t involved with this study, has researched the associations between osteoporotic fracture risk, hospitalization, and death in patients with cirrhosis.

“Current guidelines support assessing post-liver transplant patients for bone density but do not currently advocate for doing so in patients with cirrhosis or alcohol-associated liver disease, who are a much larger at-risk population,” Dr. Patel said.

“The current paper supports the idea that we should consider the broad ramifications of alcohol use on bone health for our patients and suggests that there should be greater efforts to screen for and manage osteoporosis and osteopenia in our patients earlier,” he added.

The researchers were supported by grants from Region Stockholm and the Syskonen Svensson Foundation, though the funders had no role in the conduct of the study. The study authors reported no other disclosures or conflicts of interest. Dr. Tapper and Dr. Patel report no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).

The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.

iStock/thinkstock

The findings were published online in the New England Journal of Medicine.

Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.

“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.

“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.

These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.

“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.

The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.

The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.

Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.

Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.

The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.

Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.

The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.

Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.

“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.

Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.

The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.

The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
 

Expert commentary

“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.

“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.

Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”

The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).

The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.

iStock/thinkstock

The findings were published online in the New England Journal of Medicine.

Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.

“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.

“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.

These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.

“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.

The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.

The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.

Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.

Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.

The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.

Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.

The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.

Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.

“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.

Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.

The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.

The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
 

Expert commentary

“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.

“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.

Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”

The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).

The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.

iStock/thinkstock

The findings were published online in the New England Journal of Medicine.

Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.

“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.

“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.

These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.

“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.

The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.

The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.

Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.

Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.

The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.

Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.

The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.

Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.

“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.

Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.

The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.

The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
 

Expert commentary

“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.

“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.

Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”

The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Similar to a phenomenon already well documented in women, inadequate nutrition appears to be linked to hormonal abnormalities and potentially preventable tibial cortical bone density loss in athletic men, according to results of a small, prospective study.

Based on these findings, “we suspect that a subset of male runners might not be fueling their bodies with enough nutrition and calories for their physical activity,” reported Melanie S. Haines, MD, at the annual meeting of the Endocrine Society.

This is not the first study to suggest male athletes are at risk of a condition equivalent to what has been commonly referred to as the female athlete triad, but it enlarges the objective data that the phenomenon is real, and it makes insufficient availability of energy the likely cause.

In women, the triad is described as a lack of adequate stored energy, irregular menses, and bone density loss. In men, menstrual cycles are not relevant, of course, but this study like others suggests a link between the failure to maintain adequate stores of energy, disturbances in hormone function, and decreased bone density in both men and women, Dr. Haines explained.
 

RED-S vs. male or female athlete triad

“There is now a move away from the term female athlete triad or male athlete triad,” Dr. Haines reported. Rather the factors of failing to maintain adequate energy for metabolic demands, hormonal disturbances, and bone density loss appear to be relevant to both sexes, according to Dr. Haines, an endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. She said several groups, including the International Olympic Committee (IOC), have transitioned to the term RED-S to apply to both sexes.

“RED-S is an acronym for relative energy deficiency in sport, and it appears to be gaining traction,” Dr. Haines said in an interview.

According to her study and others, excessive lean body mass from failure to supply sufficient energy for physiological needs “negatively affects hormones and bone,” Dr. Haines explained. In men and women, endocrine disturbances are triggered when insufficient calories lead to inadequate macro- and micronutrients.

In this study, 31 men aged 16-30 years were evaluated. Fifteen were in the athlete group, defined by running at least 30 miles per week for at least the previous 6 months. There were 16 control subjects; all exercised less than 2 hours per week and did not participate in team sports, but they were not permitted in the study if their body mass index exceeded 27.5 kg/m².
 

Athletes vs. otherwise healthy controls

Conditions that affect bone health were exclusion criteria in both groups, and neither group was permitted to take medications affecting bone health other than dietary calcium or vitamin D supplements for 2 months prior to the study.

Tibial cortical porosity was significantly greater – signaling deterioration in microarchitecture – in athletes, compared with control subjects (P = .003), according to quantitative computed tomography measurements. There was also significantly lower tibial cortical bone mineral density (P = .008) among athletes relative to controls.

Conversely, tibial trabecular measures of bone density and architecture were better among athletes than controls, but this was expected and did not contradict the hypothesis of the study.

“Trabecular bone refers to the inner part of the bone, which increases with weight-bearing exercise, but cortical bone is the outer shell, and the source of stress fractures,” Dr. Haines explained.

The median age of both the athletes and the controls was 24 years. Baseline measurements were similar. Body mass index, fat mass, estradiol, and leptin were all numerically lower in the athletes than controls, but none were significant, although there was a trend for the difference in leptin (P = .085).
 

Hormones correlated with tibial failure load

When these characteristics were evaluated in the context of mean tibial failure load, a metric related to strength, there was a strongly significant positive association with lean body mass (R = 0.85; P < 0.001) and estradiol level (R = 0.66; P = .007). The relationship with leptin also reached significance (R = 0.59; P = .046).

Unexpectedly, there was no relationship between testosterone and tibial failure load. The reason is unclear, but Dr. Haines’s interpretation is that the relationship between specific hormonal disturbances and bone density loss “might not be as simple” as once hypothesized.

The next step is a longitudinal evaluation of the same group of athletes to follow changes in the relationship between these variables over time, according to Dr. Haines.

Eventually, with evidence that there is a causal relationship between nutrition, hormonal changes, and bone loss, the research in this area will focus on better detection of risk and prophylactic strategies.

“Intervention trials to show that we can prevent stress factors will be difficult to perform,” Dr. Haines acknowledged, but she said that preventing adverse changes in bone at relatively young ages could have implications for long-term bone health, including protection from osteoporosis later in life.

The research presented by Dr. Haines is consistent with an area of research that is several decades old, at least in females, according to Siobhan M. Statuta, MD, a sports medicine primary care specialist at the University of Virginia, Charlottesville. The evidence that the same phenomenon occurs in men is more recent, but she said that it is now well accepted the there is a parallel hormonal issue in men and women.

“It is not a question of not eating enough. Often, athletes continue to consume the same diet, but their activity increases,” Dr. Statuta explained. “The problem is that they are not supplying enough of the calories they need to sustain the energy they are expending. You might say they are not fueling their engines appropriately.”

In 2014, the International Olympic Committee published a consensus statement on RED-S. They described this as a condition in which a state of energy deficiency leads to numerous complications in athletes, not just osteoporosis. Rather, a host of physiological systems, ranging from gastrointestinal complaints to cardiovascular events, were described.
 

RED-S addresses health beyond bones

“The RED-S theory is better described as a spoke-and-wheel concept rather than a triad. While inadequate energy availability is important to both, RED-S places this at the center of the wheel with spokes leading to all the possible complications rather than as a first event in a limited triad,” Dr. Statuta said in an interview.

However, she noted that the term RED-S is not yet appropriate to replace that of the male and female athlete triad.

“More research is required to hash out the relationship of a body in a state of energy deficiency and how it affects the entire body, which is the principle of RED-S,” Dr. Statuta said. “There likely are scientific effects, and we are currently investigating these relationships more.”

“These are really quite similar entities but have different foci,” she added. Based on data collected over several decades, “the triad narrows in on two body systems affected by low energy – the reproductive system and bones. RED-S incorporates these same systems yet adds on many more organ systems.

The original group of researchers have remained loyal to the concept of the triad that involves inadequate availability of energy followed by hormonal irregularities and osteoporosis. This group, the Female and Male Athlete Triad Coalition, has issued publications on this topic several times. Consensus statements were updated last year.

“The premise is that the triad leading to bone loss is shared by both men and women, even if the clinical manifestations differ,” said Dr. Statuta. The most notable difference is that men do not experience menstrual irregularities, but Dr. Statuta suggested that the clinical consequences are not necessarily any less.

“Males do not have menstrual cycles as an outward marker of an endocrine disturbance, so it is harder to recognize clinically, but I think there is agreement that not having enough energy available is the trigger of endocrine changes and then bone loss is relevant to both sexes,” she said. She said this is supported by a growing body of evidence, including the data presented by Dr. Haines at the Endocrine Society meeting.

Dr. Haines and Dr. Statuta report no potential conflicts of interest.

Similar to a phenomenon already well documented in women, inadequate nutrition appears to be linked to hormonal abnormalities and potentially preventable tibial cortical bone density loss in athletic men, according to results of a small, prospective study.

Based on these findings, “we suspect that a subset of male runners might not be fueling their bodies with enough nutrition and calories for their physical activity,” reported Melanie S. Haines, MD, at the annual meeting of the Endocrine Society.

This is not the first study to suggest male athletes are at risk of a condition equivalent to what has been commonly referred to as the female athlete triad, but it enlarges the objective data that the phenomenon is real, and it makes insufficient availability of energy the likely cause.

In women, the triad is described as a lack of adequate stored energy, irregular menses, and bone density loss. In men, menstrual cycles are not relevant, of course, but this study like others suggests a link between the failure to maintain adequate stores of energy, disturbances in hormone function, and decreased bone density in both men and women, Dr. Haines explained.
 

RED-S vs. male or female athlete triad

“There is now a move away from the term female athlete triad or male athlete triad,” Dr. Haines reported. Rather the factors of failing to maintain adequate energy for metabolic demands, hormonal disturbances, and bone density loss appear to be relevant to both sexes, according to Dr. Haines, an endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. She said several groups, including the International Olympic Committee (IOC), have transitioned to the term RED-S to apply to both sexes.

“RED-S is an acronym for relative energy deficiency in sport, and it appears to be gaining traction,” Dr. Haines said in an interview.

According to her study and others, excessive lean body mass from failure to supply sufficient energy for physiological needs “negatively affects hormones and bone,” Dr. Haines explained. In men and women, endocrine disturbances are triggered when insufficient calories lead to inadequate macro- and micronutrients.

In this study, 31 men aged 16-30 years were evaluated. Fifteen were in the athlete group, defined by running at least 30 miles per week for at least the previous 6 months. There were 16 control subjects; all exercised less than 2 hours per week and did not participate in team sports, but they were not permitted in the study if their body mass index exceeded 27.5 kg/m².
 

Athletes vs. otherwise healthy controls

Conditions that affect bone health were exclusion criteria in both groups, and neither group was permitted to take medications affecting bone health other than dietary calcium or vitamin D supplements for 2 months prior to the study.

Tibial cortical porosity was significantly greater – signaling deterioration in microarchitecture – in athletes, compared with control subjects (P = .003), according to quantitative computed tomography measurements. There was also significantly lower tibial cortical bone mineral density (P = .008) among athletes relative to controls.

Conversely, tibial trabecular measures of bone density and architecture were better among athletes than controls, but this was expected and did not contradict the hypothesis of the study.

“Trabecular bone refers to the inner part of the bone, which increases with weight-bearing exercise, but cortical bone is the outer shell, and the source of stress fractures,” Dr. Haines explained.

The median age of both the athletes and the controls was 24 years. Baseline measurements were similar. Body mass index, fat mass, estradiol, and leptin were all numerically lower in the athletes than controls, but none were significant, although there was a trend for the difference in leptin (P = .085).
 

Hormones correlated with tibial failure load

When these characteristics were evaluated in the context of mean tibial failure load, a metric related to strength, there was a strongly significant positive association with lean body mass (R = 0.85; P < 0.001) and estradiol level (R = 0.66; P = .007). The relationship with leptin also reached significance (R = 0.59; P = .046).

Unexpectedly, there was no relationship between testosterone and tibial failure load. The reason is unclear, but Dr. Haines’s interpretation is that the relationship between specific hormonal disturbances and bone density loss “might not be as simple” as once hypothesized.

The next step is a longitudinal evaluation of the same group of athletes to follow changes in the relationship between these variables over time, according to Dr. Haines.

Eventually, with evidence that there is a causal relationship between nutrition, hormonal changes, and bone loss, the research in this area will focus on better detection of risk and prophylactic strategies.

“Intervention trials to show that we can prevent stress factors will be difficult to perform,” Dr. Haines acknowledged, but she said that preventing adverse changes in bone at relatively young ages could have implications for long-term bone health, including protection from osteoporosis later in life.

The research presented by Dr. Haines is consistent with an area of research that is several decades old, at least in females, according to Siobhan M. Statuta, MD, a sports medicine primary care specialist at the University of Virginia, Charlottesville. The evidence that the same phenomenon occurs in men is more recent, but she said that it is now well accepted the there is a parallel hormonal issue in men and women.

“It is not a question of not eating enough. Often, athletes continue to consume the same diet, but their activity increases,” Dr. Statuta explained. “The problem is that they are not supplying enough of the calories they need to sustain the energy they are expending. You might say they are not fueling their engines appropriately.”

In 2014, the International Olympic Committee published a consensus statement on RED-S. They described this as a condition in which a state of energy deficiency leads to numerous complications in athletes, not just osteoporosis. Rather, a host of physiological systems, ranging from gastrointestinal complaints to cardiovascular events, were described.
 

RED-S addresses health beyond bones

“The RED-S theory is better described as a spoke-and-wheel concept rather than a triad. While inadequate energy availability is important to both, RED-S places this at the center of the wheel with spokes leading to all the possible complications rather than as a first event in a limited triad,” Dr. Statuta said in an interview.

However, she noted that the term RED-S is not yet appropriate to replace that of the male and female athlete triad.

“More research is required to hash out the relationship of a body in a state of energy deficiency and how it affects the entire body, which is the principle of RED-S,” Dr. Statuta said. “There likely are scientific effects, and we are currently investigating these relationships more.”

“These are really quite similar entities but have different foci,” she added. Based on data collected over several decades, “the triad narrows in on two body systems affected by low energy – the reproductive system and bones. RED-S incorporates these same systems yet adds on many more organ systems.

The original group of researchers have remained loyal to the concept of the triad that involves inadequate availability of energy followed by hormonal irregularities and osteoporosis. This group, the Female and Male Athlete Triad Coalition, has issued publications on this topic several times. Consensus statements were updated last year.

“The premise is that the triad leading to bone loss is shared by both men and women, even if the clinical manifestations differ,” said Dr. Statuta. The most notable difference is that men do not experience menstrual irregularities, but Dr. Statuta suggested that the clinical consequences are not necessarily any less.

“Males do not have menstrual cycles as an outward marker of an endocrine disturbance, so it is harder to recognize clinically, but I think there is agreement that not having enough energy available is the trigger of endocrine changes and then bone loss is relevant to both sexes,” she said. She said this is supported by a growing body of evidence, including the data presented by Dr. Haines at the Endocrine Society meeting.

Dr. Haines and Dr. Statuta report no potential conflicts of interest.

Similar to a phenomenon already well documented in women, inadequate nutrition appears to be linked to hormonal abnormalities and potentially preventable tibial cortical bone density loss in athletic men, according to results of a small, prospective study.

Based on these findings, “we suspect that a subset of male runners might not be fueling their bodies with enough nutrition and calories for their physical activity,” reported Melanie S. Haines, MD, at the annual meeting of the Endocrine Society.

This is not the first study to suggest male athletes are at risk of a condition equivalent to what has been commonly referred to as the female athlete triad, but it enlarges the objective data that the phenomenon is real, and it makes insufficient availability of energy the likely cause.

In women, the triad is described as a lack of adequate stored energy, irregular menses, and bone density loss. In men, menstrual cycles are not relevant, of course, but this study like others suggests a link between the failure to maintain adequate stores of energy, disturbances in hormone function, and decreased bone density in both men and women, Dr. Haines explained.
 

RED-S vs. male or female athlete triad

“There is now a move away from the term female athlete triad or male athlete triad,” Dr. Haines reported. Rather the factors of failing to maintain adequate energy for metabolic demands, hormonal disturbances, and bone density loss appear to be relevant to both sexes, according to Dr. Haines, an endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. She said several groups, including the International Olympic Committee (IOC), have transitioned to the term RED-S to apply to both sexes.

“RED-S is an acronym for relative energy deficiency in sport, and it appears to be gaining traction,” Dr. Haines said in an interview.

According to her study and others, excessive lean body mass from failure to supply sufficient energy for physiological needs “negatively affects hormones and bone,” Dr. Haines explained. In men and women, endocrine disturbances are triggered when insufficient calories lead to inadequate macro- and micronutrients.

In this study, 31 men aged 16-30 years were evaluated. Fifteen were in the athlete group, defined by running at least 30 miles per week for at least the previous 6 months. There were 16 control subjects; all exercised less than 2 hours per week and did not participate in team sports, but they were not permitted in the study if their body mass index exceeded 27.5 kg/m².
 

Athletes vs. otherwise healthy controls

Conditions that affect bone health were exclusion criteria in both groups, and neither group was permitted to take medications affecting bone health other than dietary calcium or vitamin D supplements for 2 months prior to the study.

Tibial cortical porosity was significantly greater – signaling deterioration in microarchitecture – in athletes, compared with control subjects (P = .003), according to quantitative computed tomography measurements. There was also significantly lower tibial cortical bone mineral density (P = .008) among athletes relative to controls.

Conversely, tibial trabecular measures of bone density and architecture were better among athletes than controls, but this was expected and did not contradict the hypothesis of the study.

“Trabecular bone refers to the inner part of the bone, which increases with weight-bearing exercise, but cortical bone is the outer shell, and the source of stress fractures,” Dr. Haines explained.

The median age of both the athletes and the controls was 24 years. Baseline measurements were similar. Body mass index, fat mass, estradiol, and leptin were all numerically lower in the athletes than controls, but none were significant, although there was a trend for the difference in leptin (P = .085).
 

Hormones correlated with tibial failure load

When these characteristics were evaluated in the context of mean tibial failure load, a metric related to strength, there was a strongly significant positive association with lean body mass (R = 0.85; P < 0.001) and estradiol level (R = 0.66; P = .007). The relationship with leptin also reached significance (R = 0.59; P = .046).

Unexpectedly, there was no relationship between testosterone and tibial failure load. The reason is unclear, but Dr. Haines’s interpretation is that the relationship between specific hormonal disturbances and bone density loss “might not be as simple” as once hypothesized.

The next step is a longitudinal evaluation of the same group of athletes to follow changes in the relationship between these variables over time, according to Dr. Haines.

Eventually, with evidence that there is a causal relationship between nutrition, hormonal changes, and bone loss, the research in this area will focus on better detection of risk and prophylactic strategies.

“Intervention trials to show that we can prevent stress factors will be difficult to perform,” Dr. Haines acknowledged, but she said that preventing adverse changes in bone at relatively young ages could have implications for long-term bone health, including protection from osteoporosis later in life.

The research presented by Dr. Haines is consistent with an area of research that is several decades old, at least in females, according to Siobhan M. Statuta, MD, a sports medicine primary care specialist at the University of Virginia, Charlottesville. The evidence that the same phenomenon occurs in men is more recent, but she said that it is now well accepted the there is a parallel hormonal issue in men and women.

“It is not a question of not eating enough. Often, athletes continue to consume the same diet, but their activity increases,” Dr. Statuta explained. “The problem is that they are not supplying enough of the calories they need to sustain the energy they are expending. You might say they are not fueling their engines appropriately.”

In 2014, the International Olympic Committee published a consensus statement on RED-S. They described this as a condition in which a state of energy deficiency leads to numerous complications in athletes, not just osteoporosis. Rather, a host of physiological systems, ranging from gastrointestinal complaints to cardiovascular events, were described.
 

RED-S addresses health beyond bones

“The RED-S theory is better described as a spoke-and-wheel concept rather than a triad. While inadequate energy availability is important to both, RED-S places this at the center of the wheel with spokes leading to all the possible complications rather than as a first event in a limited triad,” Dr. Statuta said in an interview.

However, she noted that the term RED-S is not yet appropriate to replace that of the male and female athlete triad.

“More research is required to hash out the relationship of a body in a state of energy deficiency and how it affects the entire body, which is the principle of RED-S,” Dr. Statuta said. “There likely are scientific effects, and we are currently investigating these relationships more.”

“These are really quite similar entities but have different foci,” she added. Based on data collected over several decades, “the triad narrows in on two body systems affected by low energy – the reproductive system and bones. RED-S incorporates these same systems yet adds on many more organ systems.

The original group of researchers have remained loyal to the concept of the triad that involves inadequate availability of energy followed by hormonal irregularities and osteoporosis. This group, the Female and Male Athlete Triad Coalition, has issued publications on this topic several times. Consensus statements were updated last year.

“The premise is that the triad leading to bone loss is shared by both men and women, even if the clinical manifestations differ,” said Dr. Statuta. The most notable difference is that men do not experience menstrual irregularities, but Dr. Statuta suggested that the clinical consequences are not necessarily any less.

“Males do not have menstrual cycles as an outward marker of an endocrine disturbance, so it is harder to recognize clinically, but I think there is agreement that not having enough energy available is the trigger of endocrine changes and then bone loss is relevant to both sexes,” she said. She said this is supported by a growing body of evidence, including the data presented by Dr. Haines at the Endocrine Society meeting.

Dr. Haines and Dr. Statuta report no potential conflicts of interest.

COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.

The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m³ for PM2.5 and 25.0 mcg/m³ for PM10.

“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.

Data on more than 59,000 Italian women

Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m³ or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m³ or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 > 30 mcg/m³ and PM2.5 > 25 mcg/m³ “are considered safe … by the World Health Organization,” Dr. Adami pointed out.

“If you live in a place where the chronic exposure is less than 30 mcg/m³, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.

“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does air pollution have an immunologic effect?

In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.

“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.

The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.

The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m³ for PM2.5 and 25.0 mcg/m³ for PM10.

“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.

Data on more than 59,000 Italian women

Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m³ or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m³ or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 > 30 mcg/m³ and PM2.5 > 25 mcg/m³ “are considered safe … by the World Health Organization,” Dr. Adami pointed out.

“If you live in a place where the chronic exposure is less than 30 mcg/m³, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.

“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does air pollution have an immunologic effect?

In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.

“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.

The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.

A version of this article first appeared on Medscape.com.

COPENHAGEN – Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 mcm (PM2.5) or larger, and 10 mcm (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the annual European Congress of Rheumatology.

The results of the 7-year longitudinal study carried out across Italy from 2013 to 2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona (Italy). In addition to the current report presented at EULAR 2022, Dr. Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Dr. Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin – suggesting an increased risk of bone resorption – and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Dr. Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 mcg/m³ for PM2.5 and 25.0 mcg/m³ for PM10.

“I can tell you that [25.0 mcg/m3 for PM10] is a very high exposure. It’s not very good for your health,” Dr. Adami said.

Data on more than 59,000 Italian women

Dr. Adami and colleagues used clinical characteristics and densitometric data from Italy’s osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research’s 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person’s province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 mcg/m³ or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio, 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 mcg/m³ or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 > 30 mcg/m³ and PM2.5 > 25 mcg/m³ “are considered safe … by the World Health Organization,” Dr. Adami pointed out.

“If you live in a place where the chronic exposure is less than 30 mcg/m³, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone,” he explained.

“The cortical bone – femoral neck – seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment,” Dr. Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge (England), asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Dr. Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area – the Po River valley – is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does air pollution have an immunologic effect?

In interviews with this news organization, session comoderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

“I think it’s very important to point this out. I also think it’s very hard to rule out confounding, because when you’re living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and [the lifestyle is different],” said Dr. Bultink of Amsterdam University Medical Centers.

“It stresses that these diseases [that are associated with air pollution] although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis,” said Dr. Araújo of Hospital Cuf Cascais (Portugal) and Hospital Ortopédico de Sant’Ana, Parede, Portugal.

The study was independently supported.Dr. Adami disclosed being a shareholder of Galapagos and Theramex.

A version of this article first appeared on Medscape.com.

San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.  

Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.

Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.

“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.

Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.

While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.

About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.

Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
 

Screen men with hypogonadism or those taking steroids

“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.

Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.

Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.

But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”

ATOM Study: Significant BMD increases at key sites

The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).

The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.

Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).

Three fractures occurred in those receiving placebo and one with abaloparatide.

For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).

The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.

Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).

A version of this article first appeared on Medscape.com.

San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.  

Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.

Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.

“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.

Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.

While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.

About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.

Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
 

Screen men with hypogonadism or those taking steroids

“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.

Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.

Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.

But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”

ATOM Study: Significant BMD increases at key sites

The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).

The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.

Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).

Three fractures occurred in those receiving placebo and one with abaloparatide.

For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).

The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.

Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).

A version of this article first appeared on Medscape.com.

San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.  

Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.

Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.

“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.

Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.

While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.

About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.

Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
 

Screen men with hypogonadism or those taking steroids

“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.

Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.

Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.

But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”

ATOM Study: Significant BMD increases at key sites

The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).

The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.

Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).

Three fractures occurred in those receiving placebo and one with abaloparatide.

For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).

The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.

Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).

A version of this article first appeared on Medscape.com.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Patients who receive parathyroidectomy for mild primary hyperparathyroidism show no benefits in survival or morbidity, including fractures, cancer, or cardiovascular outcomes over more than 10 years, compared with those not receiving the surgery, results from a randomized, prospective trial show.

“In contrast to existing data showing increased mortality and cardiovascular morbidity in mild primary hyperparathyroidism, we did not find any treatment effect of parathyroidectomy on these important clinical endpoints,” report the authors of the study, published in the Annals of Internal Medicine.
 

Reason to evaluate and revise current recommendations?

With mild primary hyperparathyroidism becoming the predominant form of hyperparathyroidism, the results suggest rethinking the current recommendations for the condition, the study authors note. 

“Over the years, more active management of mild primary hyperparathyroidism has been recommended, with a widening of criteria for parathyroidectomy,” they write.

“With the low number of kidney stones (n = 5) and no effect of parathyroidectomy on fractures, there may be a need to evaluate and potentially revise the current recommendations.”

The authors of an accompanying editorial agree that “the [results] provide a strong rationale for nonoperative management of patients with mild primary hyperparathyroidism.”

“The findings suggest that most patients can be managed nonoperatively, with monitoring of serum calcium levels every 1 to 2 years or if symptoms occur,” write the editorial authors, Mark J. Bolland, PhD, and Andrew Grey, MD, of the department of medicine, University of Auckland, New Zealand.

Although parathyroidectomy is recommended for the treatment in patients with hyperparathyroidism with severe hypercalcemia or overt symptoms, there has been debate on the long-term benefits of surgery among those with milder cases.  

Most previous studies that have shown benefits, such as reductions in the risk of fracture with parathyroidectomy, have importantly not distinguished between mild and more severe primary hyperparathyroidism, the authors note.
 

No significant differences in mortality between surgery, nonsurgery groups

For the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, first author Mikkel Pretorius, MD, Oslo University Hospital and Faculty of Medicine, University of Oslo, and colleagues enrolled 191 patients between 1998 and 2005 in Sweden, Norway, and Denmark, who were aged 50-80 years and had mild primary hyperparathyroidism, defined as serum calcium levels of 10.42-11.22 mg/dL.

Participants were randomized to receive surgery (n = 95) or nonoperative observation without intervention (n = 96).

After a 10-year follow-up, 129 patients had completed the final visit. The overall death rate was 7.6%, and, with eight deaths in the surgery group and seven in the nonsurgery group, there were no significant differences between groups in terms of mortality (HR, 1.17; P = .76).

During an extended observation period that lasted until 2018, mortality rates increased by 23%, but with a relatively even distribution of 24 deaths in the surgery group and 20 among those with no surgery.

Chronic hypercalcemia related to primary hyperparathyroidism has been debated as being associated with an increased risk of cardiovascular disease or cancer, however, “the absolute numbers for these and the other disease-specific causes of death were nearly identical between groups,” the authors write, with 17 deaths from cardiovascular disease, eight from cancer, and eight from cerebrovascular disease.

In terms of morbidity, including cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones, there were 101 events overall, with 52 in the parathyroidectomy group and 49 in the nonsurgery group, which again, was not a significant difference.

Sixteen vertebral fractures occurred overall in 14 patients, which were evenly split at seven patients in each group.

The authors note that “the incidence of peripheral fractures for women in our study was around 2,900 per 100,000 person-years, in the same range as for 70-year-old women in a study in Gothenburg, Sweden (about 2,600 per 100,000 person-years).”

There were no between-group differences in terms of time to death or first morbidity event for any of the prespecified events.

Of the 96 patients originally assigned to the nonsurgery group, 17 (18%) had surgery during follow-up, including three for serious hypercalcemia, three by their own choice, two for decreasing bone density, one for kidney stones, and the others for unclear or unrelated reasons.

Study limitations include that only 26 men (13 in each group) were included, and only 16 completed the study. “The external validity for men based on this study is therefore limited,” the authors note.

And although most people with primary hyperparathyroidism are adults, the older age of participants suggests the results should not be generalized to younger patients with benign parathyroid tumors.

The editorialists note that age should be one of the few factors that may, indeed, suggest appropriate candidates for parathyroidectomy.

“Younger patients (aged < 50 years) may have more aggressive disease,” they explain.

In addition, “patients with serum calcium levels above 3 mmol/L (> 12 mg/dL) are at greater risk for symptomatic hypercalcemia, and patients with a recent history of kidney stones may have fewer future stones after surgical cure.”

“Yet, such patients are a small minority of those with primary hyperparathyroidism,” they note.

The study authors underscore that “our data add evidence to guide the decisionmaking process in deliberative dialogue between clinicians and patients.”

The study received funding from Swedish government grants, the Norwegian Research Council, and the South-Eastern Norway Regional Health Authority.

A version of this article first appeared on Medscape.com.

Patients who receive parathyroidectomy for mild primary hyperparathyroidism show no benefits in survival or morbidity, including fractures, cancer, or cardiovascular outcomes over more than 10 years, compared with those not receiving the surgery, results from a randomized, prospective trial show.

“In contrast to existing data showing increased mortality and cardiovascular morbidity in mild primary hyperparathyroidism, we did not find any treatment effect of parathyroidectomy on these important clinical endpoints,” report the authors of the study, published in the Annals of Internal Medicine.
 

Reason to evaluate and revise current recommendations?

With mild primary hyperparathyroidism becoming the predominant form of hyperparathyroidism, the results suggest rethinking the current recommendations for the condition, the study authors note. 

“Over the years, more active management of mild primary hyperparathyroidism has been recommended, with a widening of criteria for parathyroidectomy,” they write.

“With the low number of kidney stones (n = 5) and no effect of parathyroidectomy on fractures, there may be a need to evaluate and potentially revise the current recommendations.”

The authors of an accompanying editorial agree that “the [results] provide a strong rationale for nonoperative management of patients with mild primary hyperparathyroidism.”

“The findings suggest that most patients can be managed nonoperatively, with monitoring of serum calcium levels every 1 to 2 years or if symptoms occur,” write the editorial authors, Mark J. Bolland, PhD, and Andrew Grey, MD, of the department of medicine, University of Auckland, New Zealand.

Although parathyroidectomy is recommended for the treatment in patients with hyperparathyroidism with severe hypercalcemia or overt symptoms, there has been debate on the long-term benefits of surgery among those with milder cases.  

Most previous studies that have shown benefits, such as reductions in the risk of fracture with parathyroidectomy, have importantly not distinguished between mild and more severe primary hyperparathyroidism, the authors note.
 

No significant differences in mortality between surgery, nonsurgery groups

For the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, first author Mikkel Pretorius, MD, Oslo University Hospital and Faculty of Medicine, University of Oslo, and colleagues enrolled 191 patients between 1998 and 2005 in Sweden, Norway, and Denmark, who were aged 50-80 years and had mild primary hyperparathyroidism, defined as serum calcium levels of 10.42-11.22 mg/dL.

Participants were randomized to receive surgery (n = 95) or nonoperative observation without intervention (n = 96).

After a 10-year follow-up, 129 patients had completed the final visit. The overall death rate was 7.6%, and, with eight deaths in the surgery group and seven in the nonsurgery group, there were no significant differences between groups in terms of mortality (HR, 1.17; P = .76).

During an extended observation period that lasted until 2018, mortality rates increased by 23%, but with a relatively even distribution of 24 deaths in the surgery group and 20 among those with no surgery.

Chronic hypercalcemia related to primary hyperparathyroidism has been debated as being associated with an increased risk of cardiovascular disease or cancer, however, “the absolute numbers for these and the other disease-specific causes of death were nearly identical between groups,” the authors write, with 17 deaths from cardiovascular disease, eight from cancer, and eight from cerebrovascular disease.

In terms of morbidity, including cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones, there were 101 events overall, with 52 in the parathyroidectomy group and 49 in the nonsurgery group, which again, was not a significant difference.

Sixteen vertebral fractures occurred overall in 14 patients, which were evenly split at seven patients in each group.

The authors note that “the incidence of peripheral fractures for women in our study was around 2,900 per 100,000 person-years, in the same range as for 70-year-old women in a study in Gothenburg, Sweden (about 2,600 per 100,000 person-years).”

There were no between-group differences in terms of time to death or first morbidity event for any of the prespecified events.

Of the 96 patients originally assigned to the nonsurgery group, 17 (18%) had surgery during follow-up, including three for serious hypercalcemia, three by their own choice, two for decreasing bone density, one for kidney stones, and the others for unclear or unrelated reasons.

Study limitations include that only 26 men (13 in each group) were included, and only 16 completed the study. “The external validity for men based on this study is therefore limited,” the authors note.

And although most people with primary hyperparathyroidism are adults, the older age of participants suggests the results should not be generalized to younger patients with benign parathyroid tumors.

The editorialists note that age should be one of the few factors that may, indeed, suggest appropriate candidates for parathyroidectomy.

“Younger patients (aged < 50 years) may have more aggressive disease,” they explain.

In addition, “patients with serum calcium levels above 3 mmol/L (> 12 mg/dL) are at greater risk for symptomatic hypercalcemia, and patients with a recent history of kidney stones may have fewer future stones after surgical cure.”

“Yet, such patients are a small minority of those with primary hyperparathyroidism,” they note.

The study authors underscore that “our data add evidence to guide the decisionmaking process in deliberative dialogue between clinicians and patients.”

The study received funding from Swedish government grants, the Norwegian Research Council, and the South-Eastern Norway Regional Health Authority.

A version of this article first appeared on Medscape.com.

Patients who receive parathyroidectomy for mild primary hyperparathyroidism show no benefits in survival or morbidity, including fractures, cancer, or cardiovascular outcomes over more than 10 years, compared with those not receiving the surgery, results from a randomized, prospective trial show.

“In contrast to existing data showing increased mortality and cardiovascular morbidity in mild primary hyperparathyroidism, we did not find any treatment effect of parathyroidectomy on these important clinical endpoints,” report the authors of the study, published in the Annals of Internal Medicine.
 

Reason to evaluate and revise current recommendations?

With mild primary hyperparathyroidism becoming the predominant form of hyperparathyroidism, the results suggest rethinking the current recommendations for the condition, the study authors note. 

“Over the years, more active management of mild primary hyperparathyroidism has been recommended, with a widening of criteria for parathyroidectomy,” they write.

“With the low number of kidney stones (n = 5) and no effect of parathyroidectomy on fractures, there may be a need to evaluate and potentially revise the current recommendations.”

The authors of an accompanying editorial agree that “the [results] provide a strong rationale for nonoperative management of patients with mild primary hyperparathyroidism.”

“The findings suggest that most patients can be managed nonoperatively, with monitoring of serum calcium levels every 1 to 2 years or if symptoms occur,” write the editorial authors, Mark J. Bolland, PhD, and Andrew Grey, MD, of the department of medicine, University of Auckland, New Zealand.

Although parathyroidectomy is recommended for the treatment in patients with hyperparathyroidism with severe hypercalcemia or overt symptoms, there has been debate on the long-term benefits of surgery among those with milder cases.  

Most previous studies that have shown benefits, such as reductions in the risk of fracture with parathyroidectomy, have importantly not distinguished between mild and more severe primary hyperparathyroidism, the authors note.
 

No significant differences in mortality between surgery, nonsurgery groups

For the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, first author Mikkel Pretorius, MD, Oslo University Hospital and Faculty of Medicine, University of Oslo, and colleagues enrolled 191 patients between 1998 and 2005 in Sweden, Norway, and Denmark, who were aged 50-80 years and had mild primary hyperparathyroidism, defined as serum calcium levels of 10.42-11.22 mg/dL.

Participants were randomized to receive surgery (n = 95) or nonoperative observation without intervention (n = 96).

After a 10-year follow-up, 129 patients had completed the final visit. The overall death rate was 7.6%, and, with eight deaths in the surgery group and seven in the nonsurgery group, there were no significant differences between groups in terms of mortality (HR, 1.17; P = .76).

During an extended observation period that lasted until 2018, mortality rates increased by 23%, but with a relatively even distribution of 24 deaths in the surgery group and 20 among those with no surgery.

Chronic hypercalcemia related to primary hyperparathyroidism has been debated as being associated with an increased risk of cardiovascular disease or cancer, however, “the absolute numbers for these and the other disease-specific causes of death were nearly identical between groups,” the authors write, with 17 deaths from cardiovascular disease, eight from cancer, and eight from cerebrovascular disease.

In terms of morbidity, including cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones, there were 101 events overall, with 52 in the parathyroidectomy group and 49 in the nonsurgery group, which again, was not a significant difference.

Sixteen vertebral fractures occurred overall in 14 patients, which were evenly split at seven patients in each group.

The authors note that “the incidence of peripheral fractures for women in our study was around 2,900 per 100,000 person-years, in the same range as for 70-year-old women in a study in Gothenburg, Sweden (about 2,600 per 100,000 person-years).”

There were no between-group differences in terms of time to death or first morbidity event for any of the prespecified events.

Of the 96 patients originally assigned to the nonsurgery group, 17 (18%) had surgery during follow-up, including three for serious hypercalcemia, three by their own choice, two for decreasing bone density, one for kidney stones, and the others for unclear or unrelated reasons.

Study limitations include that only 26 men (13 in each group) were included, and only 16 completed the study. “The external validity for men based on this study is therefore limited,” the authors note.

And although most people with primary hyperparathyroidism are adults, the older age of participants suggests the results should not be generalized to younger patients with benign parathyroid tumors.

The editorialists note that age should be one of the few factors that may, indeed, suggest appropriate candidates for parathyroidectomy.

“Younger patients (aged < 50 years) may have more aggressive disease,” they explain.

In addition, “patients with serum calcium levels above 3 mmol/L (> 12 mg/dL) are at greater risk for symptomatic hypercalcemia, and patients with a recent history of kidney stones may have fewer future stones after surgical cure.”

“Yet, such patients are a small minority of those with primary hyperparathyroidism,” they note.

The study authors underscore that “our data add evidence to guide the decisionmaking process in deliberative dialogue between clinicians and patients.”

The study received funding from Swedish government grants, the Norwegian Research Council, and the South-Eastern Norway Regional Health Authority.

A version of this article first appeared on Medscape.com.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.

Doctors’ opinions about whether to treat women with osteoporosis with hormone therapy vary. Guidelines by medical societies including those of the American College of Physicians, on the other hand, generally do not recommend it as a first line therapy for the disease, at least in part due to the risks associated with taking it.

This type of hormone therapy (HT) can be given as estrogen or a combination of hormones including estrogen. The physicians interviewed for this piece who prescribe HT for osteoporosis suggest the benefits outweigh the downsides to its use for some of their patients. But such doctors may be a minority group, suggests Michael R. McClung, MD, founding director of the Oregon Osteoporosis Center, Portland.

According to Dr. McClung, HT is now rarely prescribed as treatment – as opposed to prevention – for osteoporosis in the absence of additional benefits such as reducing vasomotor symptoms.

Researchers’ findings on HT use in women with osteoporosis are complex. While HT is approved for menopausal prevention of osteoporosis, it is not indicated as a treatment for the disease by the Food and Drug Administration. See the prescribing information for Premarin tablets, which contain a mixture of estrogen hormones, for an example of the FDA’s indications and usage for the type of HT addressed in this article.
 

Women’s Health Initiative findings

The Women’s Health Initiative (WHI) hormone therapy trials showed that HT reduces the incidence of all osteoporosis-related fractures in postmenopausal women, even those at low risk of fracture, but osteoporosis-related fractures was not a study endpoint. These trials also revealed that HT was associated with increased risks of cardiovascular and cerebrovascular events, an increased risk of breast cancer, and other adverse health outcomes.

The release of the interim results of the WHI trials in 2002 led to a fair amount of fear and confusion about the use of HT after menopause. After the WHI findings were published, estrogen use dropped dramatically, but for everything, including for vasomotor symptoms and the prevention and treatment of osteoporosis.

Prior to the WHI study, it was very common for hormone therapy to be prescribed as women neared or entered menopause, said Risa Kagan MD, clinical professor of obstetrics, gynecology, and reproductive sciences, University of California, San Francisco.

“When a woman turned 50, that was one of the first things we did – was to put her on hormone therapy. All that changed with the WHI, but now we are coming full circle,” noted Dr. Kagan, who currently prescribes HT as first line treatment for osteoporosis to some women.
 

Hormone therapy’s complex history

HT’s ability to reduce bone loss in postmenopausal women is well-documented in many papers, including one published March 8, 2018, in Osteoporosis International, by Dr. Kagan and colleagues. This reduced bone loss has been shown to significantly reduce fractures in patients with low bone mass and osteoporosis.

While a growing number of therapies are now available to treat osteoporosis, HT was traditionally viewed as a standard method of preventing fractures in this population. It was also widely used to prevent other types of symptoms associated with the menopause, such as hot flashes, night sweats, and sleep disturbances, and multiple observational studies had demonstrated that its use appeared to reduce the incidence of cardiovascular disease (CVD) in symptomatic menopausal women who initiated HT in early menopause.

Even though the WHI studies were the largest randomized trials ever performed in postmenopausal women, they had notable limitations, according to Dr. Kagan.

“The women were older – the average age was 63 years,” she said. “And they only investigated one route and one dose of estrogen.”

Since then, many different formulations and routes of administration with more favorable safety profiles than what was used in the WHI have become available.

It’s both scientifically and clinically unsound to extrapolate the unfavorable risk-benefit profile of HT seen in the WHI trials to all women regardless of age, HT dosage or formulation, or the length of time they’re on it, she added.
 

Today’s use of HT in women with osteoporosis

Re-analyses and follow-up studies from the WHI trials, along with data from other studies, have suggested that the benefit-risk profiles of HT are affected by a variety of factors. These include the timing of use in relation to menopause and chronological age and the type of hormone regimen.

“Clinically, many advocate for [hormone therapy] use, especially in the newer younger postmenopausal women to prevent bone loss, but also in younger women who are diagnosed with osteoporosis and then as they get older transition to more bone specific agents,” noted Dr. Kagan.

“Some advocate preserving bone mass and preventing osteoporosis and even treating the younger newly postmenopausal women who have no contraindications with hormone therapy initially, and then gradually transitioning them to a bone specific agent as they get older and at risk for fracture.

“If a woman is already fractured and/or has very low bone density with no other obvious secondary metabolic reason, we also often advocate anabolic agents for 1-2 years then consider estrogen for maintenance – again, if [there is] no contraindication to using HT,” she added.

Thus, an individualized approach is recommended to determine a woman’s risk-benefit ratio of HT use based on the absolute risk of adverse effects, Dr. Kagan noted.

“Transdermal and low/ultra-low doses of HT, have a favorable risk profile, and are effective in preserving bone mineral density and bone quality in many women,” she said.

According to Dr. McClung, HT “is most often used for treatment in women in whom hormone therapy was begun for hot flashes and then, when osteoporosis was found later, was simply continued.

“Society guidelines are cautious about recommending hormone therapy for osteoporosis treatment since estrogen is not approved for treatment, despite the clear fracture protection benefit observed in the WHI study,” he said. “Since [women in the WHI trials] were not recruited as having osteoporosis, those results do not meet the FDA requirement for treatment approval, namely the reduction in fracture risk in patients with osteoporosis. However, knowing what we know about the salutary skeletal effects of estrogen, many of us do use them in our patients with osteoporosis – although not prescribed for that purpose.”
 

Additional scenarios when doctors may advise HT

“I often recommend – and I think colleagues do as well – that women with recent menopause and menopausal symptoms who also have low bone mineral density or even scores showing osteoporosis see their gynecologist to discuss HT for a few years, perhaps until age 60 if no contraindications, and if it is well tolerated,” said Ethel S. Siris, MD, professor of medicine at Columbia University Medical Center in New York.

“Once they stop it we can then give one of our other bone drugs, but it delays the need to start them since on adequate estrogen the bone density should remain stable while they take it,” added Dr. Siris, an endocrinologist and internist, and director of the Toni Stabile Osteoporosis Center in New York. “They may need a bisphosphonate or another bone drug to further protect them from bone loss and future fracture [after stopping HT].”

Victor L. Roberts, MD, founder of Endocrine Associates of Florida, Lake Mary, pointed out that women now have many options for treatment of osteoporosis.

“If a woman is in early menopause and is having other symptoms, then estrogen is warranted,” he said. “If she has osteoporosis, then it’s a bonus.”

“We have better agents that are bone specific,” for a patient who presents with osteoporosis and no other symptoms, he said.

“If a woman is intolerant of alendronate or other similar drugs, or chooses not to have an injectable, then estrogen or a SERM [selective estrogen receptor modulator] would be an option.”

Dr. Roberts added that HT would be more of a niche drug.

“It has a role and documented benefit and works,” he said. “There is good scientific data for the use of estrogen.”

Dr. Kagan is a consultant for Pfizer, Therapeutics MD, Amgen, on the Medical and Scientific Advisory Board of American Bone Health. The other  experts interviewed for this piece reported no conflicts.