Nancy Walsh

MONT TREMBLANT, QUE. — Abatacept and infliximab exhibit different characteristics in their propensity to elicit autoantibody seroconversion and in their immunogenicity profiles in patients with rheumatoid arthritis, according to findings from a new analysis of data from a multicenter phase III trial.

As with all immunomodulatory agents, the development of autoimmune disorders and the formation of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) is of concern in patients who are being treated with abatacept or infliximab, said Dr. Jacques Brown of le Centre Hospitalier Universitaire de Quebec.

Recombinant biologic agents also have the potential to elicit immunogenicity, and the associated antibodies might mediate drug clearance or prevent its binding to its pharmacologic target.

Moreover, antibodies against anti-tumor necrosis factor therapy have been associated with decreased efficacy and an increased risk of infusion reactions, according to Dr. Brown.

The current analysis investigated 431 patients with rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive either abatacept, 10 mg/kg, on days 1, 15, and 29, and every 4 weeks thereafter; or infliximab, 3 mg/kg on days 1, 15, 43, and 85, and every 56 days thereafter for 6 months; or placebo.

Patients' mean age was 49 years and mean disease duration was 8 years. All had active disease, with a mean Disease Activity Score 28 of 6.8, tender joint counts above 30 and swollen joint counts above 20, and poor physical function on the Health Assessment Questionnaire Disability Index.

At baseline, 87% of the patients who were receiving abatacept were rheumatoid-factor positive, as were 85% of those patients who were randomized to the infliximab group.

At 6 months, 2% of the abatacept group, 5% of the placebo group, and 32% of the infliximab group had become ANA positive, whereas 1%, 4%, and 39% of these groups had seroconverted to positivity for anti-dsDNA antibodies, Dr. Brown reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

By 1 year, 7% of patients in the abatacept group and 48% of the infliximab group had become ANA positive, whereas 2% of the abatacept group and 48% of the infliximab group had become anti-dsDNA positive.

The patients initially randomized to placebo were switched to abatacept at 6 months and were not included in this analysis.

During the 6-month double-blind phase of the trial, none of the abatacept-treated patients developed antibodies against the drug, whereas 62% of the infliximab-treated patients had developed anti-infliximab antibodies.

During the double-blind phase, one patient in each group developed an autoimmune disorder.

One patient on abatacept developed vasculitis, one patient receiving placebo developed leukocytoclastic vasculitis, and one patient on infliximab developed sicca syndrome.

By 1 year, one additional patient who originally was randomized to placebo and later was switched to abatacept developed vasculitis.

Infusion reactions, which most commonly consisted of hypotension, headache, and nausea, were seen in 5%, 10%, and 18% of patients in the abatacept, placebo, and infliximab groups, respectively.

By 1 year these reactions were seen in 7% and 25% of the abatacept and infliximab groups.

The profiles of ANA and anti-dsDNA antibodies were markedly different in the two active treatment groups, although this difference did not translate into an increase in autoimmunity, with very few patients developing autoimmune disorders.

Furthermore, because vasculitis and sicca syndrome are associated with rheumatoid arthritis, it is difficult to determine whether the association is with the disease or with the use of biologic agents, Dr. Brown wrote.

The clinical impact of these differences remains to be elucidated, he added.

The study was sponsored by Bristol-Myers Squibb Co.

MONT TREMBLANT, QUE. — Abatacept and infliximab exhibit different characteristics in their propensity to elicit autoantibody seroconversion and in their immunogenicity profiles in patients with rheumatoid arthritis, according to findings from a new analysis of data from a multicenter phase III trial.

As with all immunomodulatory agents, the development of autoimmune disorders and the formation of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) is of concern in patients who are being treated with abatacept or infliximab, said Dr. Jacques Brown of le Centre Hospitalier Universitaire de Quebec.

Recombinant biologic agents also have the potential to elicit immunogenicity, and the associated antibodies might mediate drug clearance or prevent its binding to its pharmacologic target.

Moreover, antibodies against anti-tumor necrosis factor therapy have been associated with decreased efficacy and an increased risk of infusion reactions, according to Dr. Brown.

The current analysis investigated 431 patients with rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive either abatacept, 10 mg/kg, on days 1, 15, and 29, and every 4 weeks thereafter; or infliximab, 3 mg/kg on days 1, 15, 43, and 85, and every 56 days thereafter for 6 months; or placebo.

Patients' mean age was 49 years and mean disease duration was 8 years. All had active disease, with a mean Disease Activity Score 28 of 6.8, tender joint counts above 30 and swollen joint counts above 20, and poor physical function on the Health Assessment Questionnaire Disability Index.

At baseline, 87% of the patients who were receiving abatacept were rheumatoid-factor positive, as were 85% of those patients who were randomized to the infliximab group.

At 6 months, 2% of the abatacept group, 5% of the placebo group, and 32% of the infliximab group had become ANA positive, whereas 1%, 4%, and 39% of these groups had seroconverted to positivity for anti-dsDNA antibodies, Dr. Brown reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

By 1 year, 7% of patients in the abatacept group and 48% of the infliximab group had become ANA positive, whereas 2% of the abatacept group and 48% of the infliximab group had become anti-dsDNA positive.

The patients initially randomized to placebo were switched to abatacept at 6 months and were not included in this analysis.

During the 6-month double-blind phase of the trial, none of the abatacept-treated patients developed antibodies against the drug, whereas 62% of the infliximab-treated patients had developed anti-infliximab antibodies.

During the double-blind phase, one patient in each group developed an autoimmune disorder.

One patient on abatacept developed vasculitis, one patient receiving placebo developed leukocytoclastic vasculitis, and one patient on infliximab developed sicca syndrome.

By 1 year, one additional patient who originally was randomized to placebo and later was switched to abatacept developed vasculitis.

Infusion reactions, which most commonly consisted of hypotension, headache, and nausea, were seen in 5%, 10%, and 18% of patients in the abatacept, placebo, and infliximab groups, respectively.

By 1 year these reactions were seen in 7% and 25% of the abatacept and infliximab groups.

The profiles of ANA and anti-dsDNA antibodies were markedly different in the two active treatment groups, although this difference did not translate into an increase in autoimmunity, with very few patients developing autoimmune disorders.

Furthermore, because vasculitis and sicca syndrome are associated with rheumatoid arthritis, it is difficult to determine whether the association is with the disease or with the use of biologic agents, Dr. Brown wrote.

The clinical impact of these differences remains to be elucidated, he added.

The study was sponsored by Bristol-Myers Squibb Co.

MONT TREMBLANT, QUE. — Abatacept and infliximab exhibit different characteristics in their propensity to elicit autoantibody seroconversion and in their immunogenicity profiles in patients with rheumatoid arthritis, according to findings from a new analysis of data from a multicenter phase III trial.

As with all immunomodulatory agents, the development of autoimmune disorders and the formation of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) is of concern in patients who are being treated with abatacept or infliximab, said Dr. Jacques Brown of le Centre Hospitalier Universitaire de Quebec.

Recombinant biologic agents also have the potential to elicit immunogenicity, and the associated antibodies might mediate drug clearance or prevent its binding to its pharmacologic target.

Moreover, antibodies against anti-tumor necrosis factor therapy have been associated with decreased efficacy and an increased risk of infusion reactions, according to Dr. Brown.

The current analysis investigated 431 patients with rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive either abatacept, 10 mg/kg, on days 1, 15, and 29, and every 4 weeks thereafter; or infliximab, 3 mg/kg on days 1, 15, 43, and 85, and every 56 days thereafter for 6 months; or placebo.

Patients' mean age was 49 years and mean disease duration was 8 years. All had active disease, with a mean Disease Activity Score 28 of 6.8, tender joint counts above 30 and swollen joint counts above 20, and poor physical function on the Health Assessment Questionnaire Disability Index.

At baseline, 87% of the patients who were receiving abatacept were rheumatoid-factor positive, as were 85% of those patients who were randomized to the infliximab group.

At 6 months, 2% of the abatacept group, 5% of the placebo group, and 32% of the infliximab group had become ANA positive, whereas 1%, 4%, and 39% of these groups had seroconverted to positivity for anti-dsDNA antibodies, Dr. Brown reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

By 1 year, 7% of patients in the abatacept group and 48% of the infliximab group had become ANA positive, whereas 2% of the abatacept group and 48% of the infliximab group had become anti-dsDNA positive.

The patients initially randomized to placebo were switched to abatacept at 6 months and were not included in this analysis.

During the 6-month double-blind phase of the trial, none of the abatacept-treated patients developed antibodies against the drug, whereas 62% of the infliximab-treated patients had developed anti-infliximab antibodies.

During the double-blind phase, one patient in each group developed an autoimmune disorder.

One patient on abatacept developed vasculitis, one patient receiving placebo developed leukocytoclastic vasculitis, and one patient on infliximab developed sicca syndrome.

By 1 year, one additional patient who originally was randomized to placebo and later was switched to abatacept developed vasculitis.

Infusion reactions, which most commonly consisted of hypotension, headache, and nausea, were seen in 5%, 10%, and 18% of patients in the abatacept, placebo, and infliximab groups, respectively.

By 1 year these reactions were seen in 7% and 25% of the abatacept and infliximab groups.

The profiles of ANA and anti-dsDNA antibodies were markedly different in the two active treatment groups, although this difference did not translate into an increase in autoimmunity, with very few patients developing autoimmune disorders.

Furthermore, because vasculitis and sicca syndrome are associated with rheumatoid arthritis, it is difficult to determine whether the association is with the disease or with the use of biologic agents, Dr. Brown wrote.

The clinical impact of these differences remains to be elucidated, he added.

The study was sponsored by Bristol-Myers Squibb Co.

NEW YORK — Overtreatment for low bone mass has been all too common in women aged 50–60 years since the introduction of the bisphosphonate drugs and the widespread use of bone scans, according to Dr. Stephen Honig.

Routine bone scanning at menopause—very common in this country—creates difficulties in treatment decisions for clinicians, because when low bone density is uncovered in the early postmenopausal years it generally is in the range of osteopenia, not osteoporosis.

“A common scenario has been a 50-year-old woman who has her last period, goes for a bone scan, and has a spinal T score of −2.2. She's given a prescription for Fosamax, and 10 years later she's still on the drug,” Dr. Honig said at a rheumatology meeting sponsored by New York University.

It's important to recognize that for women in the early years after menopause, a bone mineral density measurement does not provide the clinician with enough information to make appropriate treatment decisions.

What is needed is an understanding of an individual woman's risk of fracture in the short and intermediate term, balanced against the consequences of adverse events and the possibility of subtrochanteric fractures associated with excessive suppression of bone turnover.

“We want to avoid overtreating—too much drug, too soon, for too long—and of course we also want to avoid undertreating,” he said, adding that many women in their 60s and most women in their 70s can benefit from bone-strengthening therapy.

“For women in their 50s, however, what we really need to know is who is at risk for fracture, not just who has osteopenia,” said Dr. Honig of New York University, New York.

Fractures in women of this age are not simply a result of bone loss. Fractures occur when mechanical forces overcome the bone's capacity for resistance. This bone strength is dependent on structural and material properties of the bone, including size, shape, trabecular architecture, and mineral-to-matrix ratio.

Clearly, other factors also contribute. In the National Osteoporosis Risk Assessment (NORA), which included 200,160 women aged 50 years and older, factors significantly associated with fractures included low bone mineral density, poor health status, personal or family history of fracture, maternal history of osteoporosis, no current hormone replacement therapy, menopause before age 40, corticosteroid use, and current smoking.

Analysis of the NORA data also found that the most important determinants of 3-year fracture risk in women aged 50–64 years were prior fracture, T score at or below −1.1, and self-reported fair/poor health status, with fracture risks of 7.2%, 3.1%, and 2.4%, respectively (Osteoporos. Int. 2007;18:1287–96).

A further difference in fracture risk between women in the early postmenopausal years and those who are older is that the fracture of primary concern is not the hip, but the wrist/forearm. In the Danish Osteoporosis Prevention Study, 872 women whose mean age was 51 years were followed for 10 years.

During that time, 80 fractures occurred in 78 women. There were a total of 64 in the forearm, 8 in the spine, 7 in the proximal humerus, and only 1 in the hip (J. Bone Miner. Res. 2006;21:796–800).

Studies have shown that at menopause, the rate of falls among women begins to increase dramatically. In a study from the United Kingdom that analyzed 90,061 accidents, 38,737 were classified as “underfoot” (events such as slipping or tripping). Among women overall, 51% of accidents were underfoot, as were 32% of accidents in men, but after the age of 50 these numbers increased to 64% in women and 43% in men (Q. J. Med. 2001;94:699–707).

It turns out estrogen has a critical role in postural stability, Dr. Honig said. Declining estradiol levels are associated with decreasing ability to maintain balance, slower reaction and movement times, and lower muscle strength—all of which contribute to falling and injury.

“Most clinicians never give a second thought to the issue of balance in a 50-year-old woman,” Dr. Honig said.

Having a fall-related fracture also is a risk factor for an additional fracture. Longer-term follow-up of the NORA cohort found that over 3 years, a prior wrist fracture increased the risk of a future wrist fracture about threefold and doubled the risk of any osteoporotic fracture (Osteoporos. Int. 2008;19:607–13).

In conclusion, healthy young postmenopausal women with low bone mass and no recent fracture history have a low 1- to 3-year risk of fracturing, Dr. Honig said. For these patients, according to new 2008 guidelines from the National Osteoporosis Foundation, treatment should be initiated only if their 10-year hip fracture probability is 3% or greater or their 10-year all-fracture probability is 20% or greater, based on the U.S.-adapted World Health Organization absolute fracture risk model.

The guidelines are available on the Web site of the National Osteoporosis Foundation, at www.nof.orgwww.shef.ac.uk/FRAX

Dr. Honig serves on the speakers bureau of Novartis Pharmaceuticals Corp.

Subtrochanteric fracture is seen in a patient who had been on bisphosphonate therapy. BMD measurement alone may not accurately predict fracture risk.

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK — Overtreatment for low bone mass has been all too common in women aged 50–60 years since the introduction of the bisphosphonate drugs and the widespread use of bone scans, according to Dr. Stephen Honig.

Routine bone scanning at menopause—very common in this country—creates difficulties in treatment decisions for clinicians, because when low bone density is uncovered in the early postmenopausal years it generally is in the range of osteopenia, not osteoporosis.

“A common scenario has been a 50-year-old woman who has her last period, goes for a bone scan, and has a spinal T score of −2.2. She's given a prescription for Fosamax, and 10 years later she's still on the drug,” Dr. Honig said at a rheumatology meeting sponsored by New York University.

It's important to recognize that for women in the early years after menopause, a bone mineral density measurement does not provide the clinician with enough information to make appropriate treatment decisions.

What is needed is an understanding of an individual woman's risk of fracture in the short and intermediate term, balanced against the consequences of adverse events and the possibility of subtrochanteric fractures associated with excessive suppression of bone turnover.

“We want to avoid overtreating—too much drug, too soon, for too long—and of course we also want to avoid undertreating,” he said, adding that many women in their 60s and most women in their 70s can benefit from bone-strengthening therapy.

“For women in their 50s, however, what we really need to know is who is at risk for fracture, not just who has osteopenia,” said Dr. Honig of New York University, New York.

Fractures in women of this age are not simply a result of bone loss. Fractures occur when mechanical forces overcome the bone's capacity for resistance. This bone strength is dependent on structural and material properties of the bone, including size, shape, trabecular architecture, and mineral-to-matrix ratio.

Clearly, other factors also contribute. In the National Osteoporosis Risk Assessment (NORA), which included 200,160 women aged 50 years and older, factors significantly associated with fractures included low bone mineral density, poor health status, personal or family history of fracture, maternal history of osteoporosis, no current hormone replacement therapy, menopause before age 40, corticosteroid use, and current smoking.

Analysis of the NORA data also found that the most important determinants of 3-year fracture risk in women aged 50–64 years were prior fracture, T score at or below −1.1, and self-reported fair/poor health status, with fracture risks of 7.2%, 3.1%, and 2.4%, respectively (Osteoporos. Int. 2007;18:1287–96).

A further difference in fracture risk between women in the early postmenopausal years and those who are older is that the fracture of primary concern is not the hip, but the wrist/forearm. In the Danish Osteoporosis Prevention Study, 872 women whose mean age was 51 years were followed for 10 years.

During that time, 80 fractures occurred in 78 women. There were a total of 64 in the forearm, 8 in the spine, 7 in the proximal humerus, and only 1 in the hip (J. Bone Miner. Res. 2006;21:796–800).

Studies have shown that at menopause, the rate of falls among women begins to increase dramatically. In a study from the United Kingdom that analyzed 90,061 accidents, 38,737 were classified as “underfoot” (events such as slipping or tripping). Among women overall, 51% of accidents were underfoot, as were 32% of accidents in men, but after the age of 50 these numbers increased to 64% in women and 43% in men (Q. J. Med. 2001;94:699–707).

It turns out estrogen has a critical role in postural stability, Dr. Honig said. Declining estradiol levels are associated with decreasing ability to maintain balance, slower reaction and movement times, and lower muscle strength—all of which contribute to falling and injury.

“Most clinicians never give a second thought to the issue of balance in a 50-year-old woman,” Dr. Honig said.

Having a fall-related fracture also is a risk factor for an additional fracture. Longer-term follow-up of the NORA cohort found that over 3 years, a prior wrist fracture increased the risk of a future wrist fracture about threefold and doubled the risk of any osteoporotic fracture (Osteoporos. Int. 2008;19:607–13).

In conclusion, healthy young postmenopausal women with low bone mass and no recent fracture history have a low 1- to 3-year risk of fracturing, Dr. Honig said. For these patients, according to new 2008 guidelines from the National Osteoporosis Foundation, treatment should be initiated only if their 10-year hip fracture probability is 3% or greater or their 10-year all-fracture probability is 20% or greater, based on the U.S.-adapted World Health Organization absolute fracture risk model.

The guidelines are available on the Web site of the National Osteoporosis Foundation, at www.nof.orgwww.shef.ac.uk/FRAX

Dr. Honig serves on the speakers bureau of Novartis Pharmaceuticals Corp.

Subtrochanteric fracture is seen in a patient who had been on bisphosphonate therapy. BMD measurement alone may not accurately predict fracture risk.

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK — Overtreatment for low bone mass has been all too common in women aged 50–60 years since the introduction of the bisphosphonate drugs and the widespread use of bone scans, according to Dr. Stephen Honig.

Routine bone scanning at menopause—very common in this country—creates difficulties in treatment decisions for clinicians, because when low bone density is uncovered in the early postmenopausal years it generally is in the range of osteopenia, not osteoporosis.

“A common scenario has been a 50-year-old woman who has her last period, goes for a bone scan, and has a spinal T score of −2.2. She's given a prescription for Fosamax, and 10 years later she's still on the drug,” Dr. Honig said at a rheumatology meeting sponsored by New York University.

It's important to recognize that for women in the early years after menopause, a bone mineral density measurement does not provide the clinician with enough information to make appropriate treatment decisions.

What is needed is an understanding of an individual woman's risk of fracture in the short and intermediate term, balanced against the consequences of adverse events and the possibility of subtrochanteric fractures associated with excessive suppression of bone turnover.

“We want to avoid overtreating—too much drug, too soon, for too long—and of course we also want to avoid undertreating,” he said, adding that many women in their 60s and most women in their 70s can benefit from bone-strengthening therapy.

“For women in their 50s, however, what we really need to know is who is at risk for fracture, not just who has osteopenia,” said Dr. Honig of New York University, New York.

Fractures in women of this age are not simply a result of bone loss. Fractures occur when mechanical forces overcome the bone's capacity for resistance. This bone strength is dependent on structural and material properties of the bone, including size, shape, trabecular architecture, and mineral-to-matrix ratio.

Clearly, other factors also contribute. In the National Osteoporosis Risk Assessment (NORA), which included 200,160 women aged 50 years and older, factors significantly associated with fractures included low bone mineral density, poor health status, personal or family history of fracture, maternal history of osteoporosis, no current hormone replacement therapy, menopause before age 40, corticosteroid use, and current smoking.

Analysis of the NORA data also found that the most important determinants of 3-year fracture risk in women aged 50–64 years were prior fracture, T score at or below −1.1, and self-reported fair/poor health status, with fracture risks of 7.2%, 3.1%, and 2.4%, respectively (Osteoporos. Int. 2007;18:1287–96).

A further difference in fracture risk between women in the early postmenopausal years and those who are older is that the fracture of primary concern is not the hip, but the wrist/forearm. In the Danish Osteoporosis Prevention Study, 872 women whose mean age was 51 years were followed for 10 years.

During that time, 80 fractures occurred in 78 women. There were a total of 64 in the forearm, 8 in the spine, 7 in the proximal humerus, and only 1 in the hip (J. Bone Miner. Res. 2006;21:796–800).

Studies have shown that at menopause, the rate of falls among women begins to increase dramatically. In a study from the United Kingdom that analyzed 90,061 accidents, 38,737 were classified as “underfoot” (events such as slipping or tripping). Among women overall, 51% of accidents were underfoot, as were 32% of accidents in men, but after the age of 50 these numbers increased to 64% in women and 43% in men (Q. J. Med. 2001;94:699–707).

It turns out estrogen has a critical role in postural stability, Dr. Honig said. Declining estradiol levels are associated with decreasing ability to maintain balance, slower reaction and movement times, and lower muscle strength—all of which contribute to falling and injury.

“Most clinicians never give a second thought to the issue of balance in a 50-year-old woman,” Dr. Honig said.

Having a fall-related fracture also is a risk factor for an additional fracture. Longer-term follow-up of the NORA cohort found that over 3 years, a prior wrist fracture increased the risk of a future wrist fracture about threefold and doubled the risk of any osteoporotic fracture (Osteoporos. Int. 2008;19:607–13).

In conclusion, healthy young postmenopausal women with low bone mass and no recent fracture history have a low 1- to 3-year risk of fracturing, Dr. Honig said. For these patients, according to new 2008 guidelines from the National Osteoporosis Foundation, treatment should be initiated only if their 10-year hip fracture probability is 3% or greater or their 10-year all-fracture probability is 20% or greater, based on the U.S.-adapted World Health Organization absolute fracture risk model.

The guidelines are available on the Web site of the National Osteoporosis Foundation, at www.nof.orgwww.shef.ac.uk/FRAX

Dr. Honig serves on the speakers bureau of Novartis Pharmaceuticals Corp.

Subtrochanteric fracture is seen in a patient who had been on bisphosphonate therapy. BMD measurement alone may not accurately predict fracture risk.

ELSEVIER GLOBAL MEDICAL NEWS

Adolescents who had televisions in their bedrooms had less physical activity, poorer dietary habits, and worse school performance than did adolescents without bedroom televisions, reported investigators from the University of Minnesota School of Public Health, Minneapolis.

Daheia J. Barr-Anderson, Ph.D., and colleagues found that nearly two-thirds of adolescents aged 15–18 years had a television (TV) in their bedrooms, even though the American Academy of Pediatrics recommends against this.

A total of 781 ethnically and socioeconomically diverse teens participated in Project Eating Among Teens (EAT), answering questions about their TV viewing, dietary and exercise habits, and school performance.

Analysis of the data revealed that factors associated with the presence of a bedroom TV included gender, race/ethnicity, and socioeconomic status. The prevalence of a TV in the bedroom among boys was 68%, compared with 58% among girls, and was highest among black youths at 82%, and lowest among Asians at 39%. Among those from households with highest socioeconomic status, the prevalence was 39%, compared with 61% among those from households with low socioeconomic status (Pediatrics 2008;121:718-24).

Girls with bedroom TVs spent less time in vigorous activity (4.2 hours/week vs 5.2 hours/week, spent more time watching TV (20.7 hours/week vs. 15.2 hours/week), and had lower vegetable intake (1.7 servings/day vs. 2 servings/day) and higher sweetened beverage consumption (1.2 servings/day vs. 1 serving/day) than did girls without bedroom TVs. They also participated in fewer family meals (2.9/week vs. 3.7/week).

Boys with bedroom TVs spent more time overall watching TV (22.2 hours/week vs. 18.2 hours/week), had lower fruit intake (1.7 servings/day vs. 2.2 servings/day), and participated in fewer family meals than did those without TVs (2.9/week vs. 3.6/week). They also had lower grade point averages (2.6 compared to 2.9). These differences were all statistically significant.

The researchers expressed concern about low levels of physical activity in girls, who tend to become less active in adolescence, and about lower grade point averages in boys, who tend to spend less time reading and doing homework than their female peers. “Refraining from placing a TV in adolescents' bedrooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased TV watching,” they wrote.

ELSEVIER GLOBAL MEDICAL NEWS

Girls with bedroom TVs were less physically active and had lower vegetable intake than girls with no TV. ©amaxim/Fotolia.com

Adolescents who had televisions in their bedrooms had less physical activity, poorer dietary habits, and worse school performance than did adolescents without bedroom televisions, reported investigators from the University of Minnesota School of Public Health, Minneapolis.

Daheia J. Barr-Anderson, Ph.D., and colleagues found that nearly two-thirds of adolescents aged 15–18 years had a television (TV) in their bedrooms, even though the American Academy of Pediatrics recommends against this.

A total of 781 ethnically and socioeconomically diverse teens participated in Project Eating Among Teens (EAT), answering questions about their TV viewing, dietary and exercise habits, and school performance.

Analysis of the data revealed that factors associated with the presence of a bedroom TV included gender, race/ethnicity, and socioeconomic status. The prevalence of a TV in the bedroom among boys was 68%, compared with 58% among girls, and was highest among black youths at 82%, and lowest among Asians at 39%. Among those from households with highest socioeconomic status, the prevalence was 39%, compared with 61% among those from households with low socioeconomic status (Pediatrics 2008;121:718-24).

Girls with bedroom TVs spent less time in vigorous activity (4.2 hours/week vs 5.2 hours/week, spent more time watching TV (20.7 hours/week vs. 15.2 hours/week), and had lower vegetable intake (1.7 servings/day vs. 2 servings/day) and higher sweetened beverage consumption (1.2 servings/day vs. 1 serving/day) than did girls without bedroom TVs. They also participated in fewer family meals (2.9/week vs. 3.7/week).

Boys with bedroom TVs spent more time overall watching TV (22.2 hours/week vs. 18.2 hours/week), had lower fruit intake (1.7 servings/day vs. 2.2 servings/day), and participated in fewer family meals than did those without TVs (2.9/week vs. 3.6/week). They also had lower grade point averages (2.6 compared to 2.9). These differences were all statistically significant.

The researchers expressed concern about low levels of physical activity in girls, who tend to become less active in adolescence, and about lower grade point averages in boys, who tend to spend less time reading and doing homework than their female peers. “Refraining from placing a TV in adolescents' bedrooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased TV watching,” they wrote.

ELSEVIER GLOBAL MEDICAL NEWS

Girls with bedroom TVs were less physically active and had lower vegetable intake than girls with no TV. ©amaxim/Fotolia.com

Adolescents who had televisions in their bedrooms had less physical activity, poorer dietary habits, and worse school performance than did adolescents without bedroom televisions, reported investigators from the University of Minnesota School of Public Health, Minneapolis.

Daheia J. Barr-Anderson, Ph.D., and colleagues found that nearly two-thirds of adolescents aged 15–18 years had a television (TV) in their bedrooms, even though the American Academy of Pediatrics recommends against this.

A total of 781 ethnically and socioeconomically diverse teens participated in Project Eating Among Teens (EAT), answering questions about their TV viewing, dietary and exercise habits, and school performance.

Analysis of the data revealed that factors associated with the presence of a bedroom TV included gender, race/ethnicity, and socioeconomic status. The prevalence of a TV in the bedroom among boys was 68%, compared with 58% among girls, and was highest among black youths at 82%, and lowest among Asians at 39%. Among those from households with highest socioeconomic status, the prevalence was 39%, compared with 61% among those from households with low socioeconomic status (Pediatrics 2008;121:718-24).

Girls with bedroom TVs spent less time in vigorous activity (4.2 hours/week vs 5.2 hours/week, spent more time watching TV (20.7 hours/week vs. 15.2 hours/week), and had lower vegetable intake (1.7 servings/day vs. 2 servings/day) and higher sweetened beverage consumption (1.2 servings/day vs. 1 serving/day) than did girls without bedroom TVs. They also participated in fewer family meals (2.9/week vs. 3.7/week).

Boys with bedroom TVs spent more time overall watching TV (22.2 hours/week vs. 18.2 hours/week), had lower fruit intake (1.7 servings/day vs. 2.2 servings/day), and participated in fewer family meals than did those without TVs (2.9/week vs. 3.6/week). They also had lower grade point averages (2.6 compared to 2.9). These differences were all statistically significant.

The researchers expressed concern about low levels of physical activity in girls, who tend to become less active in adolescence, and about lower grade point averages in boys, who tend to spend less time reading and doing homework than their female peers. “Refraining from placing a TV in adolescents' bedrooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased TV watching,” they wrote.

ELSEVIER GLOBAL MEDICAL NEWS

Girls with bedroom TVs were less physically active and had lower vegetable intake than girls with no TV. ©amaxim/Fotolia.com

NEW YORK — Overtreatment for low bone mass has been all too common in women aged 50–60 years since the introduction of the bisphosphonate drugs and the widespread use of bone scans, according to Dr. Stephen Honig.

Routine bone scanning at menopause—very common in this country—creates difficulties in treatment decisions for providers, because when low bone density is uncovered in the early postmenopausal years it generally is in the range of osteopenia, not osteoporosis.

“A common scenario has been a 50-year-old woman who has her last period, goes for a bone scan, and has a spinal T score of −2.2. She's given a prescription for Fosamax, and 10 years later she's still on the drug,” Dr. Honig commented at a rheumatology meeting that was sponsored by New York University.

It is important to recognize that for women in the early years after menopause, a bone mineral density measurement does not provide enough information to make appropriate treatment decisions.

What is needed is an understanding of an individual woman's risk of fracture in the short and intermediate term, balanced against the consequences of adverse events and the possibility of subtrochanteric fractures associated with excessive suppression of bone turnover.

“We want to avoid overtreating—too much drug, too soon, for too long—and of course we also want to avoid undertreating,” he said, adding that many women in their 60s and most women in their 70s can benefit from bone-strengthening therapy.

“For women in their 50s, however, what we really need to know is who is at risk for fracture, not just who has osteopenia,” said Dr. Honig of New York University, New York.

Fractures in women of this age are not simply a result of bone loss. Fractures occur when mechanical forces overcome the bone's capacity for resistance. This bone strength is dependent on structural and material properties of the bone, including size, shape, trabecular architecture, and mineral-to-matrix ratio.

Clearly, other factors also contribute. In the National Osteoporosis Risk Assessment (NORA), which included 200,160 women aged 50 years and older, factors significantly associated with fractures included low bone mineral density, poor health status, personal or family history of fracture, maternal history of osteoporosis, no current hormone replacement therapy, menopause before age 40, corticosteroid use, and current smoking.

Analysis of the NORA data also found that the most important determinants of 3-year fracture risk in women aged 50–64 years were prior fracture, T score at or below −1.1, and self-reported fair/poor health status, with fracture risks of 7.2%, 3.1%, and 2.4%, respectively (Osteoporos. Int. 2007;18:1287–96).

A further difference in fracture risk between women in the early postmenopausal years and those who are older is that the fracture of primary concern is not the hip, but the wrist/forearm. In the Danish Osteoporosis Prevention Study, 872 women whose mean age was 51 years were followed for 10 years. During that time, 80 fractures occurred in 78 women—64 in the forearm, 8 in the spine, 7 in the proximal humerus, and only 1 in the hip (J. Bone Miner. Res. 2006;21:796–800).

Studies have shown that at menopause, the rate of falls among women begins to increase dramatically.

In a study from the United Kingdom that analyzed 90,061 accidents, 38,737 were classified as “underfoot” (events such as slipping or tripping). Among women overall, 51% of accidents were underfoot, as were 32% of accidents in men, but after the age of 50 these numbers increased to 64% in women and 43% in men (Q. J. Med. 2001;94:699–707).

It turns out estrogen has a critical role in postural stability, Dr. Honig said. Declining estradiol levels are associated with decreasing ability to maintain balance, slower reaction and movement times, and lower muscle strength—all of which contribute to falling and injury.

“Most clinicians never give a second thought to the issue of balance in a 50-year-old woman,” Dr. Honig said.

Having a fall-related fracture also is a risk factor for an additional fracture. Longer-term follow-up of the NORA cohort found that over 3 years, a prior wrist fracture increased the risk of a future wrist fracture about threefold and doubled the risk of any osteoporotic fracture (Osteoporos. Int. 2008;19:607–13).

In conclusion, healthy young postmenopausal women who have a low bone mass and no recent fracture history have a low 1- to 3-year risk of fracturing, Dr. Honig said.

For these patients, according to new 2008 guidelines from the National Osteoporosis Foundation, treatment should be initiated only if their 10-year hip fracture probability is 3% or greater or their 10-year all-fracture probability is 20% or greater, based on the U.S.-adapted World Health Organization absolute fracture risk model.

To view the guidelines, which are available on the Web site of the NOF, go to www.nof.orgwww.shef.ac.uk/FRAX

ELSEVIER GLOBAL MEDICAL NEWS

Subtrochanteric fractures can occur when bone turnover is overly suppressed.

NEW YORK — Overtreatment for low bone mass has been all too common in women aged 50–60 years since the introduction of the bisphosphonate drugs and the widespread use of bone scans, according to Dr. Stephen Honig.

Routine bone scanning at menopause—very common in this country—creates difficulties in treatment decisions for providers, because when low bone density is uncovered in the early postmenopausal years it generally is in the range of osteopenia, not osteoporosis.

“A common scenario has been a 50-year-old woman who has her last period, goes for a bone scan, and has a spinal T score of −2.2. She's given a prescription for Fosamax, and 10 years later she's still on the drug,” Dr. Honig commented at a rheumatology meeting that was sponsored by New York University.

It is important to recognize that for women in the early years after menopause, a bone mineral density measurement does not provide enough information to make appropriate treatment decisions.

What is needed is an understanding of an individual woman's risk of fracture in the short and intermediate term, balanced against the consequences of adverse events and the possibility of subtrochanteric fractures associated with excessive suppression of bone turnover.

“We want to avoid overtreating—too much drug, too soon, for too long—and of course we also want to avoid undertreating,” he said, adding that many women in their 60s and most women in their 70s can benefit from bone-strengthening therapy.

“For women in their 50s, however, what we really need to know is who is at risk for fracture, not just who has osteopenia,” said Dr. Honig of New York University, New York.

Fractures in women of this age are not simply a result of bone loss. Fractures occur when mechanical forces overcome the bone's capacity for resistance. This bone strength is dependent on structural and material properties of the bone, including size, shape, trabecular architecture, and mineral-to-matrix ratio.

Clearly, other factors also contribute. In the National Osteoporosis Risk Assessment (NORA), which included 200,160 women aged 50 years and older, factors significantly associated with fractures included low bone mineral density, poor health status, personal or family history of fracture, maternal history of osteoporosis, no current hormone replacement therapy, menopause before age 40, corticosteroid use, and current smoking.

Analysis of the NORA data also found that the most important determinants of 3-year fracture risk in women aged 50–64 years were prior fracture, T score at or below −1.1, and self-reported fair/poor health status, with fracture risks of 7.2%, 3.1%, and 2.4%, respectively (Osteoporos. Int. 2007;18:1287–96).

A further difference in fracture risk between women in the early postmenopausal years and those who are older is that the fracture of primary concern is not the hip, but the wrist/forearm. In the Danish Osteoporosis Prevention Study, 872 women whose mean age was 51 years were followed for 10 years. During that time, 80 fractures occurred in 78 women—64 in the forearm, 8 in the spine, 7 in the proximal humerus, and only 1 in the hip (J. Bone Miner. Res. 2006;21:796–800).

Studies have shown that at menopause, the rate of falls among women begins to increase dramatically.

In a study from the United Kingdom that analyzed 90,061 accidents, 38,737 were classified as “underfoot” (events such as slipping or tripping). Among women overall, 51% of accidents were underfoot, as were 32% of accidents in men, but after the age of 50 these numbers increased to 64% in women and 43% in men (Q. J. Med. 2001;94:699–707).

It turns out estrogen has a critical role in postural stability, Dr. Honig said. Declining estradiol levels are associated with decreasing ability to maintain balance, slower reaction and movement times, and lower muscle strength—all of which contribute to falling and injury.

“Most clinicians never give a second thought to the issue of balance in a 50-year-old woman,” Dr. Honig said.

Having a fall-related fracture also is a risk factor for an additional fracture. Longer-term follow-up of the NORA cohort found that over 3 years, a prior wrist fracture increased the risk of a future wrist fracture about threefold and doubled the risk of any osteoporotic fracture (Osteoporos. Int. 2008;19:607–13).

In conclusion, healthy young postmenopausal women who have a low bone mass and no recent fracture history have a low 1- to 3-year risk of fracturing, Dr. Honig said.

For these patients, according to new 2008 guidelines from the National Osteoporosis Foundation, treatment should be initiated only if their 10-year hip fracture probability is 3% or greater or their 10-year all-fracture probability is 20% or greater, based on the U.S.-adapted World Health Organization absolute fracture risk model.

To view the guidelines, which are available on the Web site of the NOF, go to www.nof.orgwww.shef.ac.uk/FRAX

ELSEVIER GLOBAL MEDICAL NEWS

Subtrochanteric fractures can occur when bone turnover is overly suppressed.

NEW YORK — Overtreatment for low bone mass has been all too common in women aged 50–60 years since the introduction of the bisphosphonate drugs and the widespread use of bone scans, according to Dr. Stephen Honig.

Routine bone scanning at menopause—very common in this country—creates difficulties in treatment decisions for providers, because when low bone density is uncovered in the early postmenopausal years it generally is in the range of osteopenia, not osteoporosis.

“A common scenario has been a 50-year-old woman who has her last period, goes for a bone scan, and has a spinal T score of −2.2. She's given a prescription for Fosamax, and 10 years later she's still on the drug,” Dr. Honig commented at a rheumatology meeting that was sponsored by New York University.

It is important to recognize that for women in the early years after menopause, a bone mineral density measurement does not provide enough information to make appropriate treatment decisions.

What is needed is an understanding of an individual woman's risk of fracture in the short and intermediate term, balanced against the consequences of adverse events and the possibility of subtrochanteric fractures associated with excessive suppression of bone turnover.

“We want to avoid overtreating—too much drug, too soon, for too long—and of course we also want to avoid undertreating,” he said, adding that many women in their 60s and most women in their 70s can benefit from bone-strengthening therapy.

“For women in their 50s, however, what we really need to know is who is at risk for fracture, not just who has osteopenia,” said Dr. Honig of New York University, New York.

Fractures in women of this age are not simply a result of bone loss. Fractures occur when mechanical forces overcome the bone's capacity for resistance. This bone strength is dependent on structural and material properties of the bone, including size, shape, trabecular architecture, and mineral-to-matrix ratio.

Clearly, other factors also contribute. In the National Osteoporosis Risk Assessment (NORA), which included 200,160 women aged 50 years and older, factors significantly associated with fractures included low bone mineral density, poor health status, personal or family history of fracture, maternal history of osteoporosis, no current hormone replacement therapy, menopause before age 40, corticosteroid use, and current smoking.

Analysis of the NORA data also found that the most important determinants of 3-year fracture risk in women aged 50–64 years were prior fracture, T score at or below −1.1, and self-reported fair/poor health status, with fracture risks of 7.2%, 3.1%, and 2.4%, respectively (Osteoporos. Int. 2007;18:1287–96).

A further difference in fracture risk between women in the early postmenopausal years and those who are older is that the fracture of primary concern is not the hip, but the wrist/forearm. In the Danish Osteoporosis Prevention Study, 872 women whose mean age was 51 years were followed for 10 years. During that time, 80 fractures occurred in 78 women—64 in the forearm, 8 in the spine, 7 in the proximal humerus, and only 1 in the hip (J. Bone Miner. Res. 2006;21:796–800).

Studies have shown that at menopause, the rate of falls among women begins to increase dramatically.

In a study from the United Kingdom that analyzed 90,061 accidents, 38,737 were classified as “underfoot” (events such as slipping or tripping). Among women overall, 51% of accidents were underfoot, as were 32% of accidents in men, but after the age of 50 these numbers increased to 64% in women and 43% in men (Q. J. Med. 2001;94:699–707).

It turns out estrogen has a critical role in postural stability, Dr. Honig said. Declining estradiol levels are associated with decreasing ability to maintain balance, slower reaction and movement times, and lower muscle strength—all of which contribute to falling and injury.

“Most clinicians never give a second thought to the issue of balance in a 50-year-old woman,” Dr. Honig said.

Having a fall-related fracture also is a risk factor for an additional fracture. Longer-term follow-up of the NORA cohort found that over 3 years, a prior wrist fracture increased the risk of a future wrist fracture about threefold and doubled the risk of any osteoporotic fracture (Osteoporos. Int. 2008;19:607–13).

In conclusion, healthy young postmenopausal women who have a low bone mass and no recent fracture history have a low 1- to 3-year risk of fracturing, Dr. Honig said.

For these patients, according to new 2008 guidelines from the National Osteoporosis Foundation, treatment should be initiated only if their 10-year hip fracture probability is 3% or greater or their 10-year all-fracture probability is 20% or greater, based on the U.S.-adapted World Health Organization absolute fracture risk model.

To view the guidelines, which are available on the Web site of the NOF, go to www.nof.orgwww.shef.ac.uk/FRAX

ELSEVIER GLOBAL MEDICAL NEWS

Subtrochanteric fractures can occur when bone turnover is overly suppressed.

BOSTON — The diagnosis of syphilis is often delayed in HIV-positive patients, as it is characterized by a wide range of symptoms that may not be recognized as infection with Treponema pallidum, according to Dr. Lawrence A. Siegel of the division of international medicine and infectious diseases, Cornell University, New York.

After declining to an all-time low in 2000, the rate of syphilis in the United States rose from 3 per 100,000 population in 2001 to 5.7 per 100,000 in 2006. Syphilis has increased particularly dramatically among men who have sex with men (MSM), who made up 4% of cases in 2000 but who represented 64% of cases in 2006, Dr. Siegel reported in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

Nationwide, approximately 60% of cases of syphilis now are seen in HIV-positive, urban MSM, but in New York City, 97% of syphilis cases are in MSM.

To more fully characterize this coinfected population in New York City, Dr. Siegel and his colleagues undertook a retrospective chart review of all HIV-positive MSM diagnosed with incident syphilis at the Cornell HIV clinic between January 2001 and December 2007.

A total of 118 cases of syphilis were identified. Stage at diagnosis was primary in 8 patients, secondary in 80, early latent in 17, and late latent in 13, Dr. Siegel reported. Three patients had neurosyphilis.

Median age of the patients was 38 years. A total of 33% were white, 30% were black, 34% were Hispanic, and the rest were classified as "other."

The HIV RNA level was less than 400 copies/mL in 56%, and median CD4 count was 399 cells/mm

Clinical presentations were varied, and the diagnosis was delayed in nearly half of the patients overall. (See box.)

A total of 96% of patients had a fourfold decrease in RPR titer at 1 year, but reinfections were common, being seen at a rate of 10% per year.

A multivariate analysis found that higher baseline RPR titer and diagnosis of latent syphilis were associated with a longer time until the RPR titer became negative, Dr. Siegel reported at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Different treatment regimens—one or three doses of 2.4 million U benzathine penicillin, or doxycycline 100 mg twice daily for 30 days—were not associated with a longer time until RPR negativity, the researchers found.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The diagnosis of syphilis is often delayed in HIV-positive patients, as it is characterized by a wide range of symptoms that may not be recognized as infection with Treponema pallidum, according to Dr. Lawrence A. Siegel of the division of international medicine and infectious diseases, Cornell University, New York.

After declining to an all-time low in 2000, the rate of syphilis in the United States rose from 3 per 100,000 population in 2001 to 5.7 per 100,000 in 2006. Syphilis has increased particularly dramatically among men who have sex with men (MSM), who made up 4% of cases in 2000 but who represented 64% of cases in 2006, Dr. Siegel reported in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

Nationwide, approximately 60% of cases of syphilis now are seen in HIV-positive, urban MSM, but in New York City, 97% of syphilis cases are in MSM.

To more fully characterize this coinfected population in New York City, Dr. Siegel and his colleagues undertook a retrospective chart review of all HIV-positive MSM diagnosed with incident syphilis at the Cornell HIV clinic between January 2001 and December 2007.

A total of 118 cases of syphilis were identified. Stage at diagnosis was primary in 8 patients, secondary in 80, early latent in 17, and late latent in 13, Dr. Siegel reported. Three patients had neurosyphilis.

Median age of the patients was 38 years. A total of 33% were white, 30% were black, 34% were Hispanic, and the rest were classified as "other."

The HIV RNA level was less than 400 copies/mL in 56%, and median CD4 count was 399 cells/mm

Clinical presentations were varied, and the diagnosis was delayed in nearly half of the patients overall. (See box.)

A total of 96% of patients had a fourfold decrease in RPR titer at 1 year, but reinfections were common, being seen at a rate of 10% per year.

A multivariate analysis found that higher baseline RPR titer and diagnosis of latent syphilis were associated with a longer time until the RPR titer became negative, Dr. Siegel reported at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Different treatment regimens—one or three doses of 2.4 million U benzathine penicillin, or doxycycline 100 mg twice daily for 30 days—were not associated with a longer time until RPR negativity, the researchers found.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The diagnosis of syphilis is often delayed in HIV-positive patients, as it is characterized by a wide range of symptoms that may not be recognized as infection with Treponema pallidum, according to Dr. Lawrence A. Siegel of the division of international medicine and infectious diseases, Cornell University, New York.

After declining to an all-time low in 2000, the rate of syphilis in the United States rose from 3 per 100,000 population in 2001 to 5.7 per 100,000 in 2006. Syphilis has increased particularly dramatically among men who have sex with men (MSM), who made up 4% of cases in 2000 but who represented 64% of cases in 2006, Dr. Siegel reported in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

Nationwide, approximately 60% of cases of syphilis now are seen in HIV-positive, urban MSM, but in New York City, 97% of syphilis cases are in MSM.

To more fully characterize this coinfected population in New York City, Dr. Siegel and his colleagues undertook a retrospective chart review of all HIV-positive MSM diagnosed with incident syphilis at the Cornell HIV clinic between January 2001 and December 2007.

A total of 118 cases of syphilis were identified. Stage at diagnosis was primary in 8 patients, secondary in 80, early latent in 17, and late latent in 13, Dr. Siegel reported. Three patients had neurosyphilis.

Median age of the patients was 38 years. A total of 33% were white, 30% were black, 34% were Hispanic, and the rest were classified as "other."

The HIV RNA level was less than 400 copies/mL in 56%, and median CD4 count was 399 cells/mm

Clinical presentations were varied, and the diagnosis was delayed in nearly half of the patients overall. (See box.)

A total of 96% of patients had a fourfold decrease in RPR titer at 1 year, but reinfections were common, being seen at a rate of 10% per year.

A multivariate analysis found that higher baseline RPR titer and diagnosis of latent syphilis were associated with a longer time until the RPR titer became negative, Dr. Siegel reported at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Different treatment regimens—one or three doses of 2.4 million U benzathine penicillin, or doxycycline 100 mg twice daily for 30 days—were not associated with a longer time until RPR negativity, the researchers found.

ELSEVIER GLOBAL MEDICAL NEWS

MONT TREMBLANT, QUE. — An inflammatory mechanism may be responsible for the atrial fibrillation that occurs in some patients following the intravenous administration of potent bisphosphonates, Dr. Jason Roberts reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

In a pivotal trial of once-yearly zoledronic acid for the prevention of postmenopausal osteoporosis that randomized 7,765 women to annual infusions of active drug or placebo for 3 years, serious atrial fibrillation (AF) was seen in 1.3% of women in the zoledronic acid group compared with 0.5% of those in the placebo group.

This difference was statistically significant (N. Engl. J. Med. 2007;356:1809–22).

A letter accompanying the published study noted that a similar but nonsignificant trend had been observed in an earlier trial of alendronate. The letter stated, “Parenteral administration of bisphosphonates stimulates the release of inflammatory cytokines and increased levels of inflammatory cytokines have been associated with an increased risk of atrial fibrillation” (N. Engl. J. Med. 2007;356:1895–6).

To explore a potential connection between bisphosphonate administration and AF, a comprehensive literature review was undertaken and yielded certain mechanistic insights, according to Dr. Roberts of the University of Toronto.

“AF, once thought to be an electrical problem, is increasingly being viewed as an inflammatory condition associated with important structural changes,” Dr. Roberts wrote.

Patients with AF have increased levels of inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α, and C-reactive protein. Atrial biopsies consistently show inflammatory changes, including myocyte necrosis and fibrosis.

The principal action of bisphosphonates is inhibition of osteoclastic bone resorption, but the potent nitrogen-containing aminobisphosphonates such as zoledronic acid, alendronate, pamidronate, risedronate, and ibandronate also have proinflammatory effects, with an acute phase reaction characterized by fever and flulike symptoms occurring following a first treatment with these drugs in more than one-third of patients (Clin. Exp. Immunol. 2005;139:101–11).

This response reflects the activation and proliferation of a subset of T cells referred to as gamma-delta T cells, according to Dr. Roberts.

Another effect of aminobisphosphonates is the inhibition of farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, which is the biosynthetic route for the production of cholesterol (Ann. N.Y. Acad. Sci. 2006;1068:367–401).

Inhibition of FPPS results in accumulation of upstream metabolites including isopentenyl-5-pyrophosphate, which, like the aminobisphosphonates, directly activate gamma-delta T cells.

“Interestingly, statins, which inhibit an enzyme further upstream of IPP in the mevalonate pathway, have been shown to negate the proinflammatory effects of aminobisphosphonates,” Dr. Roberts wrote.

Given the observations that aminobisphosphonates have proinflammatory effects and that AF is an inflammatory condition, it is “reasonable” to postulate that aminobisphosphonates may increase the risk of AF through an inflammatory mechanism mediated via the mevalonate pathway, he noted.

If this turns out to be the case, the proinflammatory state associated with AF potentially could be prevented by statin therapy, he wrote.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers also have shown promise in modulating these inflammatory effects, although neither of these drugs nor any of the statins are currently recommended for the sole purpose of preventing AF (J. Am. Coll. Cardiol. 2007;50:2021–8).

ELSEVIER GLOBAL MEDICAL NEWS

MONT TREMBLANT, QUE. — An inflammatory mechanism may be responsible for the atrial fibrillation that occurs in some patients following the intravenous administration of potent bisphosphonates, Dr. Jason Roberts reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

In a pivotal trial of once-yearly zoledronic acid for the prevention of postmenopausal osteoporosis that randomized 7,765 women to annual infusions of active drug or placebo for 3 years, serious atrial fibrillation (AF) was seen in 1.3% of women in the zoledronic acid group compared with 0.5% of those in the placebo group.

This difference was statistically significant (N. Engl. J. Med. 2007;356:1809–22).

A letter accompanying the published study noted that a similar but nonsignificant trend had been observed in an earlier trial of alendronate. The letter stated, “Parenteral administration of bisphosphonates stimulates the release of inflammatory cytokines and increased levels of inflammatory cytokines have been associated with an increased risk of atrial fibrillation” (N. Engl. J. Med. 2007;356:1895–6).

To explore a potential connection between bisphosphonate administration and AF, a comprehensive literature review was undertaken and yielded certain mechanistic insights, according to Dr. Roberts of the University of Toronto.

“AF, once thought to be an electrical problem, is increasingly being viewed as an inflammatory condition associated with important structural changes,” Dr. Roberts wrote.

Patients with AF have increased levels of inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α, and C-reactive protein. Atrial biopsies consistently show inflammatory changes, including myocyte necrosis and fibrosis.

The principal action of bisphosphonates is inhibition of osteoclastic bone resorption, but the potent nitrogen-containing aminobisphosphonates such as zoledronic acid, alendronate, pamidronate, risedronate, and ibandronate also have proinflammatory effects, with an acute phase reaction characterized by fever and flulike symptoms occurring following a first treatment with these drugs in more than one-third of patients (Clin. Exp. Immunol. 2005;139:101–11).

This response reflects the activation and proliferation of a subset of T cells referred to as gamma-delta T cells, according to Dr. Roberts.

Another effect of aminobisphosphonates is the inhibition of farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, which is the biosynthetic route for the production of cholesterol (Ann. N.Y. Acad. Sci. 2006;1068:367–401).

Inhibition of FPPS results in accumulation of upstream metabolites including isopentenyl-5-pyrophosphate, which, like the aminobisphosphonates, directly activate gamma-delta T cells.

“Interestingly, statins, which inhibit an enzyme further upstream of IPP in the mevalonate pathway, have been shown to negate the proinflammatory effects of aminobisphosphonates,” Dr. Roberts wrote.

Given the observations that aminobisphosphonates have proinflammatory effects and that AF is an inflammatory condition, it is “reasonable” to postulate that aminobisphosphonates may increase the risk of AF through an inflammatory mechanism mediated via the mevalonate pathway, he noted.

If this turns out to be the case, the proinflammatory state associated with AF potentially could be prevented by statin therapy, he wrote.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers also have shown promise in modulating these inflammatory effects, although neither of these drugs nor any of the statins are currently recommended for the sole purpose of preventing AF (J. Am. Coll. Cardiol. 2007;50:2021–8).

ELSEVIER GLOBAL MEDICAL NEWS

MONT TREMBLANT, QUE. — An inflammatory mechanism may be responsible for the atrial fibrillation that occurs in some patients following the intravenous administration of potent bisphosphonates, Dr. Jason Roberts reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

In a pivotal trial of once-yearly zoledronic acid for the prevention of postmenopausal osteoporosis that randomized 7,765 women to annual infusions of active drug or placebo for 3 years, serious atrial fibrillation (AF) was seen in 1.3% of women in the zoledronic acid group compared with 0.5% of those in the placebo group.

This difference was statistically significant (N. Engl. J. Med. 2007;356:1809–22).

A letter accompanying the published study noted that a similar but nonsignificant trend had been observed in an earlier trial of alendronate. The letter stated, “Parenteral administration of bisphosphonates stimulates the release of inflammatory cytokines and increased levels of inflammatory cytokines have been associated with an increased risk of atrial fibrillation” (N. Engl. J. Med. 2007;356:1895–6).

To explore a potential connection between bisphosphonate administration and AF, a comprehensive literature review was undertaken and yielded certain mechanistic insights, according to Dr. Roberts of the University of Toronto.

“AF, once thought to be an electrical problem, is increasingly being viewed as an inflammatory condition associated with important structural changes,” Dr. Roberts wrote.

Patients with AF have increased levels of inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α, and C-reactive protein. Atrial biopsies consistently show inflammatory changes, including myocyte necrosis and fibrosis.

The principal action of bisphosphonates is inhibition of osteoclastic bone resorption, but the potent nitrogen-containing aminobisphosphonates such as zoledronic acid, alendronate, pamidronate, risedronate, and ibandronate also have proinflammatory effects, with an acute phase reaction characterized by fever and flulike symptoms occurring following a first treatment with these drugs in more than one-third of patients (Clin. Exp. Immunol. 2005;139:101–11).

This response reflects the activation and proliferation of a subset of T cells referred to as gamma-delta T cells, according to Dr. Roberts.

Another effect of aminobisphosphonates is the inhibition of farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, which is the biosynthetic route for the production of cholesterol (Ann. N.Y. Acad. Sci. 2006;1068:367–401).

Inhibition of FPPS results in accumulation of upstream metabolites including isopentenyl-5-pyrophosphate, which, like the aminobisphosphonates, directly activate gamma-delta T cells.

“Interestingly, statins, which inhibit an enzyme further upstream of IPP in the mevalonate pathway, have been shown to negate the proinflammatory effects of aminobisphosphonates,” Dr. Roberts wrote.

Given the observations that aminobisphosphonates have proinflammatory effects and that AF is an inflammatory condition, it is “reasonable” to postulate that aminobisphosphonates may increase the risk of AF through an inflammatory mechanism mediated via the mevalonate pathway, he noted.

If this turns out to be the case, the proinflammatory state associated with AF potentially could be prevented by statin therapy, he wrote.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers also have shown promise in modulating these inflammatory effects, although neither of these drugs nor any of the statins are currently recommended for the sole purpose of preventing AF (J. Am. Coll. Cardiol. 2007;50:2021–8).

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — HIV-infected patients treated with an antiretroviral regimen that included a nonnucleoside reverse transcriptase inhibitor are less likely to develop primary HIV brain pathology than are those who never received one of these agents, according to an autopsy study.

Before the era of highly active antiretroviral therapy (HAART), the incidence of inflammatory HIV brain pathology (HBP) was approximately 20%, and it is not yet clear whether antiretroviral drugs enter the brain in sufficient concentration to suppress HIV replication and prevent the development of leukoencephalopathy or microglial nodular encephalitis, Dr. Ian P. Everall said at the 15th Conference on Retroviruses and Opportunistic Infections.

To address this question, researchers performed an autopsy study on patients enrolled in the National NeuroAIDS Tissue Consortium, which was formed in 1998 to aid in research efforts to understand the effects of HIV infection on the brain. The consortium is funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

To date, more than 2,000 patients have enrolled in the consortium; these patients provide demographic, medical, and psychological data, as well as information on medications used, and they allow access to their tissues after death.

A total of 392 brains were analyzed in the first large-scale autopsy study to assess the potential influence of a class of antiretrovirals on the risk of developing HBP, said Dr. Everall, a professor of psychiatry at the University of California, San Diego.

Currently, the primary classes of HIV drugs are protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and nonnucleoside reverse transcriptase inhibitors (NNRTIs). A total of 76 patients were found to have had HBP on autopsy. When this group was compared with the non-HBP group, no differences were found in median age (45 years), sex (primarily male), or race and ethnicity. Mean disease duration was 11 years in both groups.

There also were no differences in mode of disease transmission, which was important because previous studies had suggested that certain groups such as intravenous drug users had higher rates of HBP, Dr. Everall said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

The prevalence of HBP was 28% among the 123 patients who had not received a HAART regimen during the study. Among patients whose regimens included a PI plus an NRTI, the prevalence was 22%. Among those who had received an NRTI alone, the prevalence was 17%.

The prevalence was lower, at 12%, among patients whose exposure included an NNRTI plus an NRTI or all three classes of drugs.

Multivariate analysis controlling for demographic and clinical variables, including CD4 count nadir and degree of recovery, found that the only significant predictor of HBP by drug class was the last HIV viral load measurement, which was 5.3 log10 copies/mL in the HBP group and 4.2 log10 copies/mL in the non-HBP group.

After controlling for viral load, the class of drug exposure was no longer significant. “It's slightly confusing,” Dr. Everall said.

“We think an explanation for this is that the last viral load assessment was done within 6 months of death, but exposure to classes of antiretrovirals was cumulative over the study, with the effect of drug exposure being partly negated by the viral load,” he said.

These results cannot offer a final conclusion, Dr. Everall cautioned, but it would appear that the class of drugs and viral load together may influence the risk of HBP.

BOSTON — HIV-infected patients treated with an antiretroviral regimen that included a nonnucleoside reverse transcriptase inhibitor are less likely to develop primary HIV brain pathology than are those who never received one of these agents, according to an autopsy study.

Before the era of highly active antiretroviral therapy (HAART), the incidence of inflammatory HIV brain pathology (HBP) was approximately 20%, and it is not yet clear whether antiretroviral drugs enter the brain in sufficient concentration to suppress HIV replication and prevent the development of leukoencephalopathy or microglial nodular encephalitis, Dr. Ian P. Everall said at the 15th Conference on Retroviruses and Opportunistic Infections.

To address this question, researchers performed an autopsy study on patients enrolled in the National NeuroAIDS Tissue Consortium, which was formed in 1998 to aid in research efforts to understand the effects of HIV infection on the brain. The consortium is funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

To date, more than 2,000 patients have enrolled in the consortium; these patients provide demographic, medical, and psychological data, as well as information on medications used, and they allow access to their tissues after death.

A total of 392 brains were analyzed in the first large-scale autopsy study to assess the potential influence of a class of antiretrovirals on the risk of developing HBP, said Dr. Everall, a professor of psychiatry at the University of California, San Diego.

Currently, the primary classes of HIV drugs are protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and nonnucleoside reverse transcriptase inhibitors (NNRTIs). A total of 76 patients were found to have had HBP on autopsy. When this group was compared with the non-HBP group, no differences were found in median age (45 years), sex (primarily male), or race and ethnicity. Mean disease duration was 11 years in both groups.

There also were no differences in mode of disease transmission, which was important because previous studies had suggested that certain groups such as intravenous drug users had higher rates of HBP, Dr. Everall said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

The prevalence of HBP was 28% among the 123 patients who had not received a HAART regimen during the study. Among patients whose regimens included a PI plus an NRTI, the prevalence was 22%. Among those who had received an NRTI alone, the prevalence was 17%.

The prevalence was lower, at 12%, among patients whose exposure included an NNRTI plus an NRTI or all three classes of drugs.

Multivariate analysis controlling for demographic and clinical variables, including CD4 count nadir and degree of recovery, found that the only significant predictor of HBP by drug class was the last HIV viral load measurement, which was 5.3 log10 copies/mL in the HBP group and 4.2 log10 copies/mL in the non-HBP group.

After controlling for viral load, the class of drug exposure was no longer significant. “It's slightly confusing,” Dr. Everall said.

“We think an explanation for this is that the last viral load assessment was done within 6 months of death, but exposure to classes of antiretrovirals was cumulative over the study, with the effect of drug exposure being partly negated by the viral load,” he said.

These results cannot offer a final conclusion, Dr. Everall cautioned, but it would appear that the class of drugs and viral load together may influence the risk of HBP.

BOSTON — HIV-infected patients treated with an antiretroviral regimen that included a nonnucleoside reverse transcriptase inhibitor are less likely to develop primary HIV brain pathology than are those who never received one of these agents, according to an autopsy study.

Before the era of highly active antiretroviral therapy (HAART), the incidence of inflammatory HIV brain pathology (HBP) was approximately 20%, and it is not yet clear whether antiretroviral drugs enter the brain in sufficient concentration to suppress HIV replication and prevent the development of leukoencephalopathy or microglial nodular encephalitis, Dr. Ian P. Everall said at the 15th Conference on Retroviruses and Opportunistic Infections.

To address this question, researchers performed an autopsy study on patients enrolled in the National NeuroAIDS Tissue Consortium, which was formed in 1998 to aid in research efforts to understand the effects of HIV infection on the brain. The consortium is funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

To date, more than 2,000 patients have enrolled in the consortium; these patients provide demographic, medical, and psychological data, as well as information on medications used, and they allow access to their tissues after death.

A total of 392 brains were analyzed in the first large-scale autopsy study to assess the potential influence of a class of antiretrovirals on the risk of developing HBP, said Dr. Everall, a professor of psychiatry at the University of California, San Diego.

Currently, the primary classes of HIV drugs are protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and nonnucleoside reverse transcriptase inhibitors (NNRTIs). A total of 76 patients were found to have had HBP on autopsy. When this group was compared with the non-HBP group, no differences were found in median age (45 years), sex (primarily male), or race and ethnicity. Mean disease duration was 11 years in both groups.

There also were no differences in mode of disease transmission, which was important because previous studies had suggested that certain groups such as intravenous drug users had higher rates of HBP, Dr. Everall said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

The prevalence of HBP was 28% among the 123 patients who had not received a HAART regimen during the study. Among patients whose regimens included a PI plus an NRTI, the prevalence was 22%. Among those who had received an NRTI alone, the prevalence was 17%.

The prevalence was lower, at 12%, among patients whose exposure included an NNRTI plus an NRTI or all three classes of drugs.

Multivariate analysis controlling for demographic and clinical variables, including CD4 count nadir and degree of recovery, found that the only significant predictor of HBP by drug class was the last HIV viral load measurement, which was 5.3 log10 copies/mL in the HBP group and 4.2 log10 copies/mL in the non-HBP group.

After controlling for viral load, the class of drug exposure was no longer significant. “It's slightly confusing,” Dr. Everall said.

“We think an explanation for this is that the last viral load assessment was done within 6 months of death, but exposure to classes of antiretrovirals was cumulative over the study, with the effect of drug exposure being partly negated by the viral load,” he said.

These results cannot offer a final conclusion, Dr. Everall cautioned, but it would appear that the class of drugs and viral load together may influence the risk of HBP.

MONT TREMBLANT, QUE. — Patients with rheumatoid arthritis treated with abatacept for 2 years reported improvements in fatigue, pain severity, and sleep, three key concerns for these patients, Dr. Anthony S. Russell reported at the annual meeting of the Canadian Rheumatology Association.

Several years ago at a meeting of the international network known as OMERACT, which formerly stood for Outcome Measures in Rheumatoid Arthritis Clinical Trials but now simply refers to Outcome Measures in Rheumatology, patients with rheumatoid arthritis (RA) were asked about their treatment priorities.

“Patients wanted to know if treatment will make them feel better, if it will get rid of pain and fatigue, and help them sleep,” said Dr. Russell of the University of Alberta, Edmonton.

Accordingly, these concerns were addressed during the open-label phase of two randomized trials of abatacept, a costimulatory modulator that inhibits full T-cell activation and reduces the proliferation of subsequent downstream inflammatory mediators such as interleukin-6 and C-reactive protein (J. Rheumatol. 2006;33:2162-6).

The two trials were the 12-month AIM (Abatacept in Inadequate Responders to Methotrexate) study and the 6-month ATTAIN (Abatacept Trial in Treatment of Anti-Tumor Necrosis Factor Inadequate Responders) study, both of which were sponsored by Bristol-Myers Squibb Co., makers of Orencia (abatacept). Patients who completed the double-blind phase of these trials and achieved at least an ACR 20 response were eligible to enroll in the 2-year open-label extension phase.

The treatment regimen in the blinded phase of the trials involved administration of a fixed dose of abatacept (approximately 10 mg/kg) on days 1, 15, 29, and every 4 weeks thereafter. Every 4-week administration was continued throughout the open-label phase.

To assess fatigue severity, patients were asked, “How much fatigue have you had because of your RA over the past week?” and rated this on a 100-mm visual analog scale (VAS).

Pain severity also was measured on a 100-mm VAS, and sleep quality was assessed using the Medical Outcomes Study Sleep Scale and a sleep problems index.

A total of 378 patients entered the long-term phase of AIM, as did 218 in ATTAIN.

Mean age of patients in AIM was 51 years, 77% were women, and the mean duration of RA was 8 years.

In ATTAIN, patients' mean age was 53 years, 77% were women, and the mean duration of RA was 12 years.

In both trials, the mean number of tender joints was 31 and the mean number of swollen joints was 22. The mean C-reactive protein level was 3.2 mg/dL in AIM and 4.6 mg/dL in ATTAIN.

At baseline in AIM, 44% of patients reported VAS scores higher than 70 for both fatigue and pain, and 9% had this degree of severity for sleep problems. After 2 years of abatacept treatment, these percentages were reduced to 10%, 4%, and 2%, respectively, Dr. Russell reported in a poster session.

Also after 2 years of treatment VAS scores below 30 were reported by 53%, 64%, and 49% for fatigue, pain, and sleep problems, respectively.

“Pain and fatigue improved markedly,” he said.

Similar results were seen in ATTAIN, despite the fact that patients in that trial were somewhat sicker.

All had failed at least one tumor necrosis factor inhibitor, and many had failed two, Dr. Russell said.

At baseline in ATTAIN, VAS scores of 70 and higher were reported by 68% of study participants for fatigue, by 58% of participants for pain, and by 13% for sleep problems.

After 2 years, these percentages had decreased to 24%, 9%, and 4%, respectively, while scores below 30 were reported by 33%, 51%, and 39%.

“By providing around-the-clock improvements in quality of life—pain and fatigue during the daytime and sleep quality during the night—abatacept has the potential to provide meaningful patient-centered benefits in moderate to severe RA,” Dr. Russell wrote.

“We can say to patients, yes, we listened to your concerns,” he said during the poster presentation.

MONT TREMBLANT, QUE. — Patients with rheumatoid arthritis treated with abatacept for 2 years reported improvements in fatigue, pain severity, and sleep, three key concerns for these patients, Dr. Anthony S. Russell reported at the annual meeting of the Canadian Rheumatology Association.

Several years ago at a meeting of the international network known as OMERACT, which formerly stood for Outcome Measures in Rheumatoid Arthritis Clinical Trials but now simply refers to Outcome Measures in Rheumatology, patients with rheumatoid arthritis (RA) were asked about their treatment priorities.

“Patients wanted to know if treatment will make them feel better, if it will get rid of pain and fatigue, and help them sleep,” said Dr. Russell of the University of Alberta, Edmonton.

Accordingly, these concerns were addressed during the open-label phase of two randomized trials of abatacept, a costimulatory modulator that inhibits full T-cell activation and reduces the proliferation of subsequent downstream inflammatory mediators such as interleukin-6 and C-reactive protein (J. Rheumatol. 2006;33:2162-6).

The two trials were the 12-month AIM (Abatacept in Inadequate Responders to Methotrexate) study and the 6-month ATTAIN (Abatacept Trial in Treatment of Anti-Tumor Necrosis Factor Inadequate Responders) study, both of which were sponsored by Bristol-Myers Squibb Co., makers of Orencia (abatacept). Patients who completed the double-blind phase of these trials and achieved at least an ACR 20 response were eligible to enroll in the 2-year open-label extension phase.

The treatment regimen in the blinded phase of the trials involved administration of a fixed dose of abatacept (approximately 10 mg/kg) on days 1, 15, 29, and every 4 weeks thereafter. Every 4-week administration was continued throughout the open-label phase.

To assess fatigue severity, patients were asked, “How much fatigue have you had because of your RA over the past week?” and rated this on a 100-mm visual analog scale (VAS).

Pain severity also was measured on a 100-mm VAS, and sleep quality was assessed using the Medical Outcomes Study Sleep Scale and a sleep problems index.

A total of 378 patients entered the long-term phase of AIM, as did 218 in ATTAIN.

Mean age of patients in AIM was 51 years, 77% were women, and the mean duration of RA was 8 years.

In ATTAIN, patients' mean age was 53 years, 77% were women, and the mean duration of RA was 12 years.

In both trials, the mean number of tender joints was 31 and the mean number of swollen joints was 22. The mean C-reactive protein level was 3.2 mg/dL in AIM and 4.6 mg/dL in ATTAIN.

At baseline in AIM, 44% of patients reported VAS scores higher than 70 for both fatigue and pain, and 9% had this degree of severity for sleep problems. After 2 years of abatacept treatment, these percentages were reduced to 10%, 4%, and 2%, respectively, Dr. Russell reported in a poster session.

Also after 2 years of treatment VAS scores below 30 were reported by 53%, 64%, and 49% for fatigue, pain, and sleep problems, respectively.

“Pain and fatigue improved markedly,” he said.

Similar results were seen in ATTAIN, despite the fact that patients in that trial were somewhat sicker.

All had failed at least one tumor necrosis factor inhibitor, and many had failed two, Dr. Russell said.

At baseline in ATTAIN, VAS scores of 70 and higher were reported by 68% of study participants for fatigue, by 58% of participants for pain, and by 13% for sleep problems.

After 2 years, these percentages had decreased to 24%, 9%, and 4%, respectively, while scores below 30 were reported by 33%, 51%, and 39%.

“By providing around-the-clock improvements in quality of life—pain and fatigue during the daytime and sleep quality during the night—abatacept has the potential to provide meaningful patient-centered benefits in moderate to severe RA,” Dr. Russell wrote.

“We can say to patients, yes, we listened to your concerns,” he said during the poster presentation.

MONT TREMBLANT, QUE. — Patients with rheumatoid arthritis treated with abatacept for 2 years reported improvements in fatigue, pain severity, and sleep, three key concerns for these patients, Dr. Anthony S. Russell reported at the annual meeting of the Canadian Rheumatology Association.

Several years ago at a meeting of the international network known as OMERACT, which formerly stood for Outcome Measures in Rheumatoid Arthritis Clinical Trials but now simply refers to Outcome Measures in Rheumatology, patients with rheumatoid arthritis (RA) were asked about their treatment priorities.

“Patients wanted to know if treatment will make them feel better, if it will get rid of pain and fatigue, and help them sleep,” said Dr. Russell of the University of Alberta, Edmonton.

Accordingly, these concerns were addressed during the open-label phase of two randomized trials of abatacept, a costimulatory modulator that inhibits full T-cell activation and reduces the proliferation of subsequent downstream inflammatory mediators such as interleukin-6 and C-reactive protein (J. Rheumatol. 2006;33:2162-6).

The two trials were the 12-month AIM (Abatacept in Inadequate Responders to Methotrexate) study and the 6-month ATTAIN (Abatacept Trial in Treatment of Anti-Tumor Necrosis Factor Inadequate Responders) study, both of which were sponsored by Bristol-Myers Squibb Co., makers of Orencia (abatacept). Patients who completed the double-blind phase of these trials and achieved at least an ACR 20 response were eligible to enroll in the 2-year open-label extension phase.

The treatment regimen in the blinded phase of the trials involved administration of a fixed dose of abatacept (approximately 10 mg/kg) on days 1, 15, 29, and every 4 weeks thereafter. Every 4-week administration was continued throughout the open-label phase.

To assess fatigue severity, patients were asked, “How much fatigue have you had because of your RA over the past week?” and rated this on a 100-mm visual analog scale (VAS).

Pain severity also was measured on a 100-mm VAS, and sleep quality was assessed using the Medical Outcomes Study Sleep Scale and a sleep problems index.

A total of 378 patients entered the long-term phase of AIM, as did 218 in ATTAIN.

Mean age of patients in AIM was 51 years, 77% were women, and the mean duration of RA was 8 years.

In ATTAIN, patients' mean age was 53 years, 77% were women, and the mean duration of RA was 12 years.

In both trials, the mean number of tender joints was 31 and the mean number of swollen joints was 22. The mean C-reactive protein level was 3.2 mg/dL in AIM and 4.6 mg/dL in ATTAIN.

At baseline in AIM, 44% of patients reported VAS scores higher than 70 for both fatigue and pain, and 9% had this degree of severity for sleep problems. After 2 years of abatacept treatment, these percentages were reduced to 10%, 4%, and 2%, respectively, Dr. Russell reported in a poster session.

Also after 2 years of treatment VAS scores below 30 were reported by 53%, 64%, and 49% for fatigue, pain, and sleep problems, respectively.

“Pain and fatigue improved markedly,” he said.

Similar results were seen in ATTAIN, despite the fact that patients in that trial were somewhat sicker.

All had failed at least one tumor necrosis factor inhibitor, and many had failed two, Dr. Russell said.

At baseline in ATTAIN, VAS scores of 70 and higher were reported by 68% of study participants for fatigue, by 58% of participants for pain, and by 13% for sleep problems.

After 2 years, these percentages had decreased to 24%, 9%, and 4%, respectively, while scores below 30 were reported by 33%, 51%, and 39%.

“By providing around-the-clock improvements in quality of life—pain and fatigue during the daytime and sleep quality during the night—abatacept has the potential to provide meaningful patient-centered benefits in moderate to severe RA,” Dr. Russell wrote.

“We can say to patients, yes, we listened to your concerns,” he said during the poster presentation.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

BOSTON — An increased risk for osteoporosis or osteopenia is among the age-related complications faced by patients surviving long term with HIV disease.

Cross-sectional studies have shown that patients with HIV have a greater prevalence of reduced bone mineral density, compared with healthy controls, but longitudinal data that would demonstrate the significance of this increased risk are lacking, said Dr. William G. Powderly of University College Dublin.

To meet this need for data, the Centers for Disease Control and Prevention is prospectively following a cohort of more than 500 HIV-infected patients in the Study to Understand the Natural History of HIV and AIDS (SUN), Dr. Powderly said at the 15th Conference on Retroviruses and Opportunistic Infections.

On enrollment in SUN, patients had baseline bone densitometry and body composition measurements, clinical data, and fasting laboratory data collected, and were matched for age, race, sex, and body mass index with controls from the National Health and Nutrition Examination Study III.

Among the SUN patients (mean age 41 years), 52% had osteopenia and 10% had frank osteoporosis, Dr. Powderly said.

A total of 78% were men, 25% were black, and almost 80% were receiving antiretroviral therapy.

Analysis revealed that factors associated with an increased risk of low bone mineral density included age over 45 years (odds ratio 2.35) and CD4 count below 300 cells/mm3 (OR 2.10), Dr. Powderly said.

Duration of HIV infection longer than 98 months also was associated with an increased risk (OR 1.56).

Determining whether bone mineral loss will continue over time and translate into increased risk for fractures is a “critically important” area of HIV research, Dr. Powderly said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

Further information also is needed on HIV-associated risk factors. Aside from risk factors also present in the general population such as smoking, alcohol use, low body mass index, and lack of physical activity, the aging HIV patient also might have renal dysfunction and inadequate nutrition, which can further contribute to bone loss. HIV disease itself might alter the processes involved in bone mineralization and turnover, according to Dr. Powderly. In a study he and his colleagues performed, human osteoblast and mesenchymal stem cell lines were treated in vitro with several HIV proteins, including HIV p55-gag and HIV gp120.

Exposure to these proteins reduced calcium deposition, alkaline phosphatase activity, and mRNA levels of osteogenic transcription factors in osteoblasts, and the ability of stem cells to develop into osteoblasts was modulated (AIDS Res. Hum. Retroviruses 2007;23:1521-30).

There is also some evidence implicating potent antiretroviral medications in bone loss. In a meta-analysis of 20 studies that included 884 patients, 67% had reduced bone mineral density and 15% had osteoporosis. Those receiving antiretroviral therapy had a 2.5-fold increased risk of having reduced bone mineral density, compared with those who were treatment naive (AIDS 2006;20:2165-74).

The dynamic process of bone mineralization is another factor. “We reach the peak of bone mineralization at around 30 years, and then both men and women lose bone at a rate of approximately 0.5%-1% per year,” according to Dr. Powderly.

Because women have lower peak bone mass than do men, they have higher rates of osteoporosis as they age. Until the relative contributions to bone loss of the various factors can be more fully clarified, the routine care of older patients with HIV should include baseline and routine monitoring of markers of bone turnover, according to Dr. Powderly.

BOSTON — An increased risk for osteoporosis or osteopenia is among the age-related complications faced by patients surviving long term with HIV disease.

Cross-sectional studies have shown that patients with HIV have a greater prevalence of reduced bone mineral density, compared with healthy controls, but longitudinal data that would demonstrate the significance of this increased risk are lacking, said Dr. William G. Powderly of University College Dublin.

To meet this need for data, the Centers for Disease Control and Prevention is prospectively following a cohort of more than 500 HIV-infected patients in the Study to Understand the Natural History of HIV and AIDS (SUN), Dr. Powderly said at the 15th Conference on Retroviruses and Opportunistic Infections.

On enrollment in SUN, patients had baseline bone densitometry and body composition measurements, clinical data, and fasting laboratory data collected, and were matched for age, race, sex, and body mass index with controls from the National Health and Nutrition Examination Study III.

Among the SUN patients (mean age 41 years), 52% had osteopenia and 10% had frank osteoporosis, Dr. Powderly said.

A total of 78% were men, 25% were black, and almost 80% were receiving antiretroviral therapy.

Analysis revealed that factors associated with an increased risk of low bone mineral density included age over 45 years (odds ratio 2.35) and CD4 count below 300 cells/mm3 (OR 2.10), Dr. Powderly said.

Duration of HIV infection longer than 98 months also was associated with an increased risk (OR 1.56).

Determining whether bone mineral loss will continue over time and translate into increased risk for fractures is a “critically important” area of HIV research, Dr. Powderly said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

Further information also is needed on HIV-associated risk factors. Aside from risk factors also present in the general population such as smoking, alcohol use, low body mass index, and lack of physical activity, the aging HIV patient also might have renal dysfunction and inadequate nutrition, which can further contribute to bone loss. HIV disease itself might alter the processes involved in bone mineralization and turnover, according to Dr. Powderly. In a study he and his colleagues performed, human osteoblast and mesenchymal stem cell lines were treated in vitro with several HIV proteins, including HIV p55-gag and HIV gp120.

Exposure to these proteins reduced calcium deposition, alkaline phosphatase activity, and mRNA levels of osteogenic transcription factors in osteoblasts, and the ability of stem cells to develop into osteoblasts was modulated (AIDS Res. Hum. Retroviruses 2007;23:1521-30).

There is also some evidence implicating potent antiretroviral medications in bone loss. In a meta-analysis of 20 studies that included 884 patients, 67% had reduced bone mineral density and 15% had osteoporosis. Those receiving antiretroviral therapy had a 2.5-fold increased risk of having reduced bone mineral density, compared with those who were treatment naive (AIDS 2006;20:2165-74).

The dynamic process of bone mineralization is another factor. “We reach the peak of bone mineralization at around 30 years, and then both men and women lose bone at a rate of approximately 0.5%-1% per year,” according to Dr. Powderly.

Because women have lower peak bone mass than do men, they have higher rates of osteoporosis as they age. Until the relative contributions to bone loss of the various factors can be more fully clarified, the routine care of older patients with HIV should include baseline and routine monitoring of markers of bone turnover, according to Dr. Powderly.

BOSTON — An increased risk for osteoporosis or osteopenia is among the age-related complications faced by patients surviving long term with HIV disease.

Cross-sectional studies have shown that patients with HIV have a greater prevalence of reduced bone mineral density, compared with healthy controls, but longitudinal data that would demonstrate the significance of this increased risk are lacking, said Dr. William G. Powderly of University College Dublin.

To meet this need for data, the Centers for Disease Control and Prevention is prospectively following a cohort of more than 500 HIV-infected patients in the Study to Understand the Natural History of HIV and AIDS (SUN), Dr. Powderly said at the 15th Conference on Retroviruses and Opportunistic Infections.

On enrollment in SUN, patients had baseline bone densitometry and body composition measurements, clinical data, and fasting laboratory data collected, and were matched for age, race, sex, and body mass index with controls from the National Health and Nutrition Examination Study III.

Among the SUN patients (mean age 41 years), 52% had osteopenia and 10% had frank osteoporosis, Dr. Powderly said.

A total of 78% were men, 25% were black, and almost 80% were receiving antiretroviral therapy.

Analysis revealed that factors associated with an increased risk of low bone mineral density included age over 45 years (odds ratio 2.35) and CD4 count below 300 cells/mm3 (OR 2.10), Dr. Powderly said.

Duration of HIV infection longer than 98 months also was associated with an increased risk (OR 1.56).

Determining whether bone mineral loss will continue over time and translate into increased risk for fractures is a “critically important” area of HIV research, Dr. Powderly said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the CDC.

Further information also is needed on HIV-associated risk factors. Aside from risk factors also present in the general population such as smoking, alcohol use, low body mass index, and lack of physical activity, the aging HIV patient also might have renal dysfunction and inadequate nutrition, which can further contribute to bone loss. HIV disease itself might alter the processes involved in bone mineralization and turnover, according to Dr. Powderly. In a study he and his colleagues performed, human osteoblast and mesenchymal stem cell lines were treated in vitro with several HIV proteins, including HIV p55-gag and HIV gp120.

Exposure to these proteins reduced calcium deposition, alkaline phosphatase activity, and mRNA levels of osteogenic transcription factors in osteoblasts, and the ability of stem cells to develop into osteoblasts was modulated (AIDS Res. Hum. Retroviruses 2007;23:1521-30).

There is also some evidence implicating potent antiretroviral medications in bone loss. In a meta-analysis of 20 studies that included 884 patients, 67% had reduced bone mineral density and 15% had osteoporosis. Those receiving antiretroviral therapy had a 2.5-fold increased risk of having reduced bone mineral density, compared with those who were treatment naive (AIDS 2006;20:2165-74).

The dynamic process of bone mineralization is another factor. “We reach the peak of bone mineralization at around 30 years, and then both men and women lose bone at a rate of approximately 0.5%-1% per year,” according to Dr. Powderly.

Because women have lower peak bone mass than do men, they have higher rates of osteoporosis as they age. Until the relative contributions to bone loss of the various factors can be more fully clarified, the routine care of older patients with HIV should include baseline and routine monitoring of markers of bone turnover, according to Dr. Powderly.