TBD Meeting (3149-23)

VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.

Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.

Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.

Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.

The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.

After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.

Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).

The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.

There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.

In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.

The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.

The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.

There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.

Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.

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

VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.

Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.

Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.

Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.

The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.

After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.

Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).

The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.

There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.

In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.

The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.

The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.

There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.

Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.

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

VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.

Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.

Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.

Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.

The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.

After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.

Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).

The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.

There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.

In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.

The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.

The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.

There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.

Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.

The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.

Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.

The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.

The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.

The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.

At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).

Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).

During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.

The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.

Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.

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

VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.

The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.

Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.

The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.

The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.

The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.

At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).

Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).

During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.

The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.

Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.

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

VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.

The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.

Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.

The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.

The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.

The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.

At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).

Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).

During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.

The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.

Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.

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

VANCOUVER – With treatment with a bisphosphonate following sequential use of teriparatide (Forteo) and denosumab (Prolia) for premenopausal women with idiopathic osteoporosis, bone mineral density (BMD) was maintained over the first year following denosumab cessation, according to results from a small, nonrandomized extension of a phase 2 study.

Bisphosphonates are recommended for patients after they have completed a course of denosumab because cessation of the bone resorption blocker is known to increase bone turnover markers, decrease BMD, and raise the risk of vertebral fractures. Although there is evidence to support this treatment sequence for postmenopausal women, there was no evidence regarding premenopausal women with idiopathic osteoporosis, said Adi Cohen, MD, who presented the results of the study at the annual meeting of the American Society for Bone and Mineral Research.

In the extension study, neither length of treatment with denosumab nor transition to menopause affected BMD results. Weekly doses of alendronate (ALN) better suppressed C-terminal telopeptide (CTX) than did zoledronic acid (ZOL) and led to better maintenance of BMD than did a single dose of ZOL. The researchers suggested that single-dose ZOL may not prevent bone loss for an entire year.

It is too early to call the results practice changing, said Dr. Cohen, professor of medicine and endocrinology at Columbia University Irving Medical Center, New York, but she noted, “It’s important just to provide information about how sequences of osteoporosis medications might be used in a rare but certainly understudied group of premenopausal women with osteoporosis who need treatment, and these data hopefully will help make some treatment decisions.”

In the early 2000s, researchers initially believed that premenopausal women with low BMD had experienced some kind of temporary event and that they would likely improve on their own over time. “I think we now recognize that whatever it is that causes this is an ongoing issue and that this is a problem they’re going to have to deal with for the rest of their lives. This is something that they have to stay on top of,” said coauthor Elizabeth Shane, MD, who is a professor of medicine at CUIMC.

However, there are no practice guidelines for the management of osteoporosis in premenopausal women, according to Dr. Shane. She noted that there is controversy as to whether to treat women with low bone density who do not have a history of fractures. “I think that there’s pretty much agreement that anybody who has a lot of fractures has an early-onset form of osteoporosis. The controversy is what to do about the person who just has a low bone density and hasn’t yet fractured and what is the utility of trying to treat them at that point and perhaps prevent a fracture. I don’t think we have enough data to address that,” Dr. Shane said.

Still, the research has provided some clarity in her own practice. “I think if somebody would come to my office who had very low bone density, I would probably treat them. If they have fractures, I would definitely treat them. I think that our work has provided a framework for people to approach that,” she said.

The study was an extension of a sequential treatment approach that began with 2 years of teriparatide (20 mcg daily) followed by an extension study of 2–3 years of treatment with denosumab (60 mg every 6 months). Seven months after the last dose of denosumab, patients underwent 1 year of treatment with ALN (70 mg weekly; n = 18) or a single dose of ZOL (5 mg IV; n = 6), according to patient choice.

The original phase 2 study started with 41 women. At 24 months, teriparatide treatment led to BMD increases of 13% in the lumbar spine (LS), 5% in the total hip (TH), and 5% in the femoral neck (FN). There was a 2% decline in BMD in the forearm (distal radius [DR]). A group of 32 of the women participated in an extension study and took denosumab for 12 months. Of those patients, 29 continued to take it for another 12 months. At 12 months, BMD increased 5% in the LS, 3% in the TH, 3% in the FN, and 1% in the DR (P < .05 for all). At 24 months, BMD rose by 22%, 10%, and 10% at the first three of those locations. BMD in the DR remained stable, compared with the baseline after taking teriparatide.

The bisphosphonate phase of the extension study included 24 women (mean age, 43 years). The mean body mass index of the patients was 23.0 kg/m². The patients had experienced a mean of 3.0 fractures in adulthood, and 38% of patients had a history of vertebral fracture.

Over 12 months of follow-up, the researchers found no statistically significant difference in BMD in the LS, TH, or FN, compared with bisphosphonate extension baseline. There was also no statistically significant change in serum CTX. There was evidence that, among patients with higher rates of bone turnover, there were higher rates of LS and FN bone loss during bisphosphonate treatment.

Among patients taking ZOL, at 12 months there was a statistically significant rise in CTX levels, but not among patients taking ALN. There were no new vertebral fractures among any participants during the bisphosphonate extension period.

The results represent critical data for an understudied population, according to Yumie Rhee, MD, PhD, who was comoderator of the session in which the study was presented. “They are showing that by using a bisphosphonate [patients] have this just slight decrease, but within error, so it’s maintaining the BMD, at least. I think it’s very important. It will be fascinating to see next year’s follow-up,” said Dr. Rhee, a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea. “The problem with premenopausal osteoporosis is that we don’t have good evidence. Even though this study is very small, we’re just following that data, all of us.”

Comoderator Maria Zanchetta, MD, a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires, agreed. “We know what to do when we stop denosumab in postmenopausal women. We didn’t have any work about what to do when we stopped in premenopausal women. You can think that probably it’s going to be the same, but this is the first time you have the evidence that if you give bisphosphonate, you will maintain BMD.”

Limitations to the study include its small size and the lack of a placebo-treated control group. In addition, the bisphosphonate extension was not randomized.

The studies were funded by the U.S. Food and Drug Administration and Amgen. Dr. Cohen and Dr. Shane received research funding from Amgen. Dr. Rhee and Dr. Zanchetta have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – With treatment with a bisphosphonate following sequential use of teriparatide (Forteo) and denosumab (Prolia) for premenopausal women with idiopathic osteoporosis, bone mineral density (BMD) was maintained over the first year following denosumab cessation, according to results from a small, nonrandomized extension of a phase 2 study.

Bisphosphonates are recommended for patients after they have completed a course of denosumab because cessation of the bone resorption blocker is known to increase bone turnover markers, decrease BMD, and raise the risk of vertebral fractures. Although there is evidence to support this treatment sequence for postmenopausal women, there was no evidence regarding premenopausal women with idiopathic osteoporosis, said Adi Cohen, MD, who presented the results of the study at the annual meeting of the American Society for Bone and Mineral Research.

In the extension study, neither length of treatment with denosumab nor transition to menopause affected BMD results. Weekly doses of alendronate (ALN) better suppressed C-terminal telopeptide (CTX) than did zoledronic acid (ZOL) and led to better maintenance of BMD than did a single dose of ZOL. The researchers suggested that single-dose ZOL may not prevent bone loss for an entire year.

It is too early to call the results practice changing, said Dr. Cohen, professor of medicine and endocrinology at Columbia University Irving Medical Center, New York, but she noted, “It’s important just to provide information about how sequences of osteoporosis medications might be used in a rare but certainly understudied group of premenopausal women with osteoporosis who need treatment, and these data hopefully will help make some treatment decisions.”

In the early 2000s, researchers initially believed that premenopausal women with low BMD had experienced some kind of temporary event and that they would likely improve on their own over time. “I think we now recognize that whatever it is that causes this is an ongoing issue and that this is a problem they’re going to have to deal with for the rest of their lives. This is something that they have to stay on top of,” said coauthor Elizabeth Shane, MD, who is a professor of medicine at CUIMC.

However, there are no practice guidelines for the management of osteoporosis in premenopausal women, according to Dr. Shane. She noted that there is controversy as to whether to treat women with low bone density who do not have a history of fractures. “I think that there’s pretty much agreement that anybody who has a lot of fractures has an early-onset form of osteoporosis. The controversy is what to do about the person who just has a low bone density and hasn’t yet fractured and what is the utility of trying to treat them at that point and perhaps prevent a fracture. I don’t think we have enough data to address that,” Dr. Shane said.

Still, the research has provided some clarity in her own practice. “I think if somebody would come to my office who had very low bone density, I would probably treat them. If they have fractures, I would definitely treat them. I think that our work has provided a framework for people to approach that,” she said.

The study was an extension of a sequential treatment approach that began with 2 years of teriparatide (20 mcg daily) followed by an extension study of 2–3 years of treatment with denosumab (60 mg every 6 months). Seven months after the last dose of denosumab, patients underwent 1 year of treatment with ALN (70 mg weekly; n = 18) or a single dose of ZOL (5 mg IV; n = 6), according to patient choice.

The original phase 2 study started with 41 women. At 24 months, teriparatide treatment led to BMD increases of 13% in the lumbar spine (LS), 5% in the total hip (TH), and 5% in the femoral neck (FN). There was a 2% decline in BMD in the forearm (distal radius [DR]). A group of 32 of the women participated in an extension study and took denosumab for 12 months. Of those patients, 29 continued to take it for another 12 months. At 12 months, BMD increased 5% in the LS, 3% in the TH, 3% in the FN, and 1% in the DR (P < .05 for all). At 24 months, BMD rose by 22%, 10%, and 10% at the first three of those locations. BMD in the DR remained stable, compared with the baseline after taking teriparatide.

The bisphosphonate phase of the extension study included 24 women (mean age, 43 years). The mean body mass index of the patients was 23.0 kg/m². The patients had experienced a mean of 3.0 fractures in adulthood, and 38% of patients had a history of vertebral fracture.

Over 12 months of follow-up, the researchers found no statistically significant difference in BMD in the LS, TH, or FN, compared with bisphosphonate extension baseline. There was also no statistically significant change in serum CTX. There was evidence that, among patients with higher rates of bone turnover, there were higher rates of LS and FN bone loss during bisphosphonate treatment.

Among patients taking ZOL, at 12 months there was a statistically significant rise in CTX levels, but not among patients taking ALN. There were no new vertebral fractures among any participants during the bisphosphonate extension period.

The results represent critical data for an understudied population, according to Yumie Rhee, MD, PhD, who was comoderator of the session in which the study was presented. “They are showing that by using a bisphosphonate [patients] have this just slight decrease, but within error, so it’s maintaining the BMD, at least. I think it’s very important. It will be fascinating to see next year’s follow-up,” said Dr. Rhee, a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea. “The problem with premenopausal osteoporosis is that we don’t have good evidence. Even though this study is very small, we’re just following that data, all of us.”

Comoderator Maria Zanchetta, MD, a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires, agreed. “We know what to do when we stop denosumab in postmenopausal women. We didn’t have any work about what to do when we stopped in premenopausal women. You can think that probably it’s going to be the same, but this is the first time you have the evidence that if you give bisphosphonate, you will maintain BMD.”

Limitations to the study include its small size and the lack of a placebo-treated control group. In addition, the bisphosphonate extension was not randomized.

The studies were funded by the U.S. Food and Drug Administration and Amgen. Dr. Cohen and Dr. Shane received research funding from Amgen. Dr. Rhee and Dr. Zanchetta have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – With treatment with a bisphosphonate following sequential use of teriparatide (Forteo) and denosumab (Prolia) for premenopausal women with idiopathic osteoporosis, bone mineral density (BMD) was maintained over the first year following denosumab cessation, according to results from a small, nonrandomized extension of a phase 2 study.

Bisphosphonates are recommended for patients after they have completed a course of denosumab because cessation of the bone resorption blocker is known to increase bone turnover markers, decrease BMD, and raise the risk of vertebral fractures. Although there is evidence to support this treatment sequence for postmenopausal women, there was no evidence regarding premenopausal women with idiopathic osteoporosis, said Adi Cohen, MD, who presented the results of the study at the annual meeting of the American Society for Bone and Mineral Research.

In the extension study, neither length of treatment with denosumab nor transition to menopause affected BMD results. Weekly doses of alendronate (ALN) better suppressed C-terminal telopeptide (CTX) than did zoledronic acid (ZOL) and led to better maintenance of BMD than did a single dose of ZOL. The researchers suggested that single-dose ZOL may not prevent bone loss for an entire year.

It is too early to call the results practice changing, said Dr. Cohen, professor of medicine and endocrinology at Columbia University Irving Medical Center, New York, but she noted, “It’s important just to provide information about how sequences of osteoporosis medications might be used in a rare but certainly understudied group of premenopausal women with osteoporosis who need treatment, and these data hopefully will help make some treatment decisions.”

In the early 2000s, researchers initially believed that premenopausal women with low BMD had experienced some kind of temporary event and that they would likely improve on their own over time. “I think we now recognize that whatever it is that causes this is an ongoing issue and that this is a problem they’re going to have to deal with for the rest of their lives. This is something that they have to stay on top of,” said coauthor Elizabeth Shane, MD, who is a professor of medicine at CUIMC.

However, there are no practice guidelines for the management of osteoporosis in premenopausal women, according to Dr. Shane. She noted that there is controversy as to whether to treat women with low bone density who do not have a history of fractures. “I think that there’s pretty much agreement that anybody who has a lot of fractures has an early-onset form of osteoporosis. The controversy is what to do about the person who just has a low bone density and hasn’t yet fractured and what is the utility of trying to treat them at that point and perhaps prevent a fracture. I don’t think we have enough data to address that,” Dr. Shane said.

Still, the research has provided some clarity in her own practice. “I think if somebody would come to my office who had very low bone density, I would probably treat them. If they have fractures, I would definitely treat them. I think that our work has provided a framework for people to approach that,” she said.

The study was an extension of a sequential treatment approach that began with 2 years of teriparatide (20 mcg daily) followed by an extension study of 2–3 years of treatment with denosumab (60 mg every 6 months). Seven months after the last dose of denosumab, patients underwent 1 year of treatment with ALN (70 mg weekly; n = 18) or a single dose of ZOL (5 mg IV; n = 6), according to patient choice.

The original phase 2 study started with 41 women. At 24 months, teriparatide treatment led to BMD increases of 13% in the lumbar spine (LS), 5% in the total hip (TH), and 5% in the femoral neck (FN). There was a 2% decline in BMD in the forearm (distal radius [DR]). A group of 32 of the women participated in an extension study and took denosumab for 12 months. Of those patients, 29 continued to take it for another 12 months. At 12 months, BMD increased 5% in the LS, 3% in the TH, 3% in the FN, and 1% in the DR (P < .05 for all). At 24 months, BMD rose by 22%, 10%, and 10% at the first three of those locations. BMD in the DR remained stable, compared with the baseline after taking teriparatide.

The bisphosphonate phase of the extension study included 24 women (mean age, 43 years). The mean body mass index of the patients was 23.0 kg/m². The patients had experienced a mean of 3.0 fractures in adulthood, and 38% of patients had a history of vertebral fracture.

Over 12 months of follow-up, the researchers found no statistically significant difference in BMD in the LS, TH, or FN, compared with bisphosphonate extension baseline. There was also no statistically significant change in serum CTX. There was evidence that, among patients with higher rates of bone turnover, there were higher rates of LS and FN bone loss during bisphosphonate treatment.

Among patients taking ZOL, at 12 months there was a statistically significant rise in CTX levels, but not among patients taking ALN. There were no new vertebral fractures among any participants during the bisphosphonate extension period.

The results represent critical data for an understudied population, according to Yumie Rhee, MD, PhD, who was comoderator of the session in which the study was presented. “They are showing that by using a bisphosphonate [patients] have this just slight decrease, but within error, so it’s maintaining the BMD, at least. I think it’s very important. It will be fascinating to see next year’s follow-up,” said Dr. Rhee, a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea. “The problem with premenopausal osteoporosis is that we don’t have good evidence. Even though this study is very small, we’re just following that data, all of us.”

Comoderator Maria Zanchetta, MD, a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires, agreed. “We know what to do when we stop denosumab in postmenopausal women. We didn’t have any work about what to do when we stopped in premenopausal women. You can think that probably it’s going to be the same, but this is the first time you have the evidence that if you give bisphosphonate, you will maintain BMD.”

Limitations to the study include its small size and the lack of a placebo-treated control group. In addition, the bisphosphonate extension was not randomized.

The studies were funded by the U.S. Food and Drug Administration and Amgen. Dr. Cohen and Dr. Shane received research funding from Amgen. Dr. Rhee and Dr. Zanchetta have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

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

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

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

VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.

The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.

As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.

“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.

Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.

The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.

Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m². Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.

The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).

The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.

Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.

Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”

Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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

VANCOUVER – A highly controlled retrospective analysis suggests that denosumab (Prolia) leads to greater reduction in fracture risk than does zoledronic acid (Reclast) among treatment-naive postmenopausal women with osteoporosis.

A previous head-to-head comparison showed that denosumab increased bone mineral density at key skeletal sites compared with zoledronic acid, but only a single, small observational study has examined fracture risk, and it found no difference.

The new study, presented at the annual meeting of the American Society for Bone and Mineral Research, used a relatively new method of real-world comparative effectiveness analysis called negative control outcome (NCO) to analyze Medicare fee-for-service data.

NCO analysis takes extra pains to remove bias through data that might be linked to potential confounders but could not reasonably be attributed to a drug. For example, people who have greater contact with the health care system may be more likely to get one drug or another. The researchers used the frequency of receiving a flu or pneumonia vaccine as a proxy for this. If the two comparison groups had a significant difference in a proxy, it suggested a hidden bias and forced the researchers to abandon those groupings. Another example used car accidents as a proxy for cognitive impairment.

“If you find meaningful differences between the two groups, and you can say there’s no way a bone drug could account for these differences, then we shouldn’t do this analysis because these groups just aren’t comparable. They probably differ by that confounding factor we couldn’t measure,” said Jeffrey Curtis, MD, who presented the study. He is a professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

The study strongly suggests superiority for denosumab. “There was a significant difference in multiple different groupings of fractures – beginning at year 2, extending to year 3 and even out to year 5 – that showed that there is a significant reduction in fracture risk if you get treated with denosumab [that was greater] than if you get treated with zoledronic acid,” Dr. Curtis said.

The researchers weighed 118 covariates and ultimately identified a population of 90,805 women taking denosumab and 37,328 taking zoledronic acid that was equally balanced in all patient characteristics. The mean age was about 75 years in the denosumab group and 74 in the zoledronic acid group.

The researchers found a 34% lower risk for hip fracture in the denosumab group by 5 years (relative risk, 0.66; 95% confidence interval, 0.43-0.90).

Similar patterns in fracture risk reduction were observed at 5 years for nonvertebral fracture (RR, 0.67; 95% CI, 0.52-0.82), nonhip nonvertebral fracture (RR, 0.69; 95% CI, 0.50-0.88), and major osteoporotic fracture (RR, 0.74; 95% CI, 0.59-0.89).

During the Q&A session after the talk, one audience member commented that the study was limited because the researchers only followed patients who received zoledronic acid for 60 days, which could have missed potential long-term benefits of the drug, especially since bisphosphonates have a lengthy skeletal retention time. Dr. Curtis acknowledged the point but said, “Usually, that’s not something we do, but these are different enough mechanisms of action that it may be warranted at least as a sensitivity analysis,” he said.

The study and its methodology were impressive, according to Yumie Rhee, MD, who comoderated the session where the study was presented. “I think they did a really good job by doing the negative control analysis. We’re not going to have a head-to-head clinical trial, so we don’t know the real fracture reduction differences [between denosumab and zoledronic acid]. [The NCO analysis] is more than the propensity matching score that we do usually,” said Dr. Rhee, who is a professor of endocrinology at Yonsei University College of Medicine in Seoul, South Korea.

In particular, the study showed a significantly greater reduction in hip fractures with denosumab. “Even in the RCTs, it was really hard to see the reduction in hip fracture, so I think this is showing much stronger data for denosumab. Especially in patients who have more [general fracture] risk and patients with higher hip fracture risk, I would go with denosumab,” Dr. Rhee said.

Her comoderator, Maria Zanchetta, MD, agreed. “It can have clinical implication, because we think denosumab is better than [zoledronic acid] for higher-risk patients, but we didn’t have the evidence. So at least we have a new [study] to look at, and I think it’s very important for our practice,” said Dr. Zanchetta, who is a professor of osteology at the Institute of Diagnostics and Metabolic Research, Universidad del Salvador, Buenos Aires.

The study was funded by Amgen, which markets denosumab. Dr. Curtis has consulted for Amgen. Dr. Rhee and Dr. Zanchetta report no relevant financial relationships.

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