Osteoporosis

WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.

Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.

“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.

Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.

The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.

The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.

In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.

The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.

Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.

Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.

Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.

“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.

Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.

The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.

The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.

In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.

The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.

Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.

Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.

Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.

“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.

Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.

The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.

The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.

In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.

The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.

Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.

Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.

“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.

The draft recommendations build upon the 2010 ACR recommendations.

“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”

Recommendations for risk assessment

Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.

For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.

“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.

FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.

A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
 

Treatment

The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.

All patients should take calcium and vitamin D, regardless of risk level.

The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).

“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.

For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.

Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.

Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.

Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.

Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.

The authors and sponsors had no relevant financial disclosures.

WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.

“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.

The draft recommendations build upon the 2010 ACR recommendations.

“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”

Recommendations for risk assessment

Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.

For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.

“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.

FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.

A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
 

Treatment

The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.

All patients should take calcium and vitamin D, regardless of risk level.

The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).

“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.

For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.

Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.

Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.

Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.

Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.

The authors and sponsors had no relevant financial disclosures.

WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.

“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.

The draft recommendations build upon the 2010 ACR recommendations.

“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”

Recommendations for risk assessment

Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.

For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.

“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.

FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.

A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
 

Treatment

The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.

All patients should take calcium and vitamin D, regardless of risk level.

The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).

“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.

For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.

Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.

Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.

Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.

Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.

The authors and sponsors had no relevant financial disclosures.

This year’s annual meeting of the American College of Rheumatology will feature cutting-edge research and results of studies that directly affect how attendees will manage patients once they are back in the clinical setting, according to both Richard Loeser, MD, program chair of the Annual Meeting Planning Committee (AMPC), and Gregory Gardner, MD, clinical subchair of the AMPC, who suggested special sessions of interest culled from the more than 450 sessions to be presented.

“It is an exciting time in rheumatology. Basic research is being translated into new therapies before our very eyes. Areas on the program this year that have translational potential include immunometabolism, blocking interleukin-1 (IL-1), T-cell receptor signaling, and meta-analysis of gene expression data. The meeting will also feature trials that refine and advance the management of rheumatologic diseases, including results on studies of new biologics,” Dr. Loeser said.

Hot sessions

Luke O’Neill, MD, will talk about immunometabolism Monday at 7:30 a.m. This session will explore a newly described connection between energy metabolism and the immune system and the link with inflammation.

Charles Dinarello, MD, will give the Philip Hensch Memorial Lecture Sunday at 8:30 a.m. on blocking IL-1 in inflammatory diseases. He will cover a host of diseases from gout to cancer, Dr. Loeser noted.

Another hot topic, T-cell receptor signaling in autoimmune diseases and the development of new therapies, will be discussed by Arthur Weiss, MD, Tuesday morning at 7:30 a.m.

Tuesday at 11:00 a.m., Peter Lipsky, MD, will tackle big data mining, presenting a meta-analysis of gene expression datasets to identify novel pathways and targets in systemic lupus erythematosus (SLE).

“SLE lags behind rheumatoid arthritis in therapeutic advances. A number of trials of biologics have failed in SLE, whereas they have been found effective in rheumatoid arthritis,” Dr. Loeser explained.

Clinical slant

Sunday’s Plenary session at 11:00 a.m. will feature several top-rated abstracts, among them results of a phase III study on tocilizumab in giant cell arteritis to be presented by John Stone, MD. “Tocilizumab is a major breakthrough as a steroid-sparing treatment for the most common form of vasculitis that affects older adults,” Dr. Loeser said.

At 2:30 p.m. on Sunday at The Great Debate, Paul Emery, MD, and Arthur Kavanaugh, MD, will tackle the very important clinical topic of “To Taper or Not to Taper? – Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity.”

“People aren’t sure what to do. The fear with tapering is rebound, with the disease coming back even more forcefully. There is new evidence to suggest that tapering may be safe under certain circumstances. This session should inform attendees on how to make the decision to taper and on the best way to do it,” Dr. Loeser commented.

The Late-Breaking Abstract session on Tuesday at 4:30 p.m. will feature six clinical trials. Dr. Loeser singled out a study to be presented by Elaine Husni, MD, on “Vascular Safety of Celecoxib versus Ibuprofen or Naproxen” in more than 20,000 patients with osteoarthritis or rheumatoid arthritis.

“The fear is that COX-2 inhibitors have increased cardiovascular risk. The data from this study that will be presented at the meeting should answer the question of whether or not this is true in patients with arthritis,” Dr. Loeser explained.

Wednesday at 7:30 a.m. Candida Fratazzi, MD, will talk about “Emerging Biosimilars in Therapeutic Management,” a subject of great interest since they have the potential to be equally effective and less expensive than current biologics.

Two “bookends” of the meeting will frame the opening and closing. Sunday at 7:30 a.m., the “Year in Review” session will feature the best published studies on rheumatologic diseases from the past year, based on the judgment of two experts. Ingrid Lundberg, MD, will present the best clinical studies and Bruce Cronstein, MD, will present the best basic science studies. Wednesday at 7:30 a.m., John Cush, MD, and Dr. Kavanaugh will present the “Rheumatology Roundup” of the best abstracts and put them into context. “This session is usually quite entertaining,” Dr. Loeser said.

More sessions of clinical import

“In keeping with our meeting theme of fine-tuning our care of patients with rheumatic disease, I want to point out several sessions,” Dr. Gardner said.

Attendees interested in sessions on clinical applicability will have to choose between two different sessions Monday at 4:30 p.m.: one on dermatomyositis, a relatively rare but difficult-to-treat entity, and the other about treatment of the patient with rheumatoid arthritis when the patient is not well and suffering from comorbidities.

Monday at 8:30 a.m., an “Osteoporosis Update” will give listeners perspective on current and future therapies.

Sunday at 2:30 p.m., new guidelines for steroid-induced osteoporosis will be presented.

“Four or five sessions on the Tech Track will show rheumatologists how they can improve their practice by using technology,” Dr. Gardner said. “Several high-quality sessions are important to educators, including ‘Flipped Classroom, Technology, and Reflection’ [Monday at 12:30 p.m.] and ‘Year in Review’ [Sunday at 1:00 p.m.].”

Monday at 11:00 a.m., the Plenary session will feature Workforce Study results on how many rheumatologists will be needed in the year 2030, and in which geographic locations. This session will also include a discussion of the impact of part-time rheumatologists.

“Two sessions I am excited about are ‘Treat to Target in 2016,’ Tuesday at 4:30 p.m., and ‘Rheumatic Diseases in Native Americans,’ Sunday at 11:00 a.m.,” Dr. Gardner noted. “Concurrent abstract sessions throughout the meeting will feature discussions on new biologics, small molecules, and gene therapy.”

This year’s annual meeting of the American College of Rheumatology will feature cutting-edge research and results of studies that directly affect how attendees will manage patients once they are back in the clinical setting, according to both Richard Loeser, MD, program chair of the Annual Meeting Planning Committee (AMPC), and Gregory Gardner, MD, clinical subchair of the AMPC, who suggested special sessions of interest culled from the more than 450 sessions to be presented.

“It is an exciting time in rheumatology. Basic research is being translated into new therapies before our very eyes. Areas on the program this year that have translational potential include immunometabolism, blocking interleukin-1 (IL-1), T-cell receptor signaling, and meta-analysis of gene expression data. The meeting will also feature trials that refine and advance the management of rheumatologic diseases, including results on studies of new biologics,” Dr. Loeser said.

Hot sessions

Luke O’Neill, MD, will talk about immunometabolism Monday at 7:30 a.m. This session will explore a newly described connection between energy metabolism and the immune system and the link with inflammation.

Charles Dinarello, MD, will give the Philip Hensch Memorial Lecture Sunday at 8:30 a.m. on blocking IL-1 in inflammatory diseases. He will cover a host of diseases from gout to cancer, Dr. Loeser noted.

Another hot topic, T-cell receptor signaling in autoimmune diseases and the development of new therapies, will be discussed by Arthur Weiss, MD, Tuesday morning at 7:30 a.m.

Tuesday at 11:00 a.m., Peter Lipsky, MD, will tackle big data mining, presenting a meta-analysis of gene expression datasets to identify novel pathways and targets in systemic lupus erythematosus (SLE).

“SLE lags behind rheumatoid arthritis in therapeutic advances. A number of trials of biologics have failed in SLE, whereas they have been found effective in rheumatoid arthritis,” Dr. Loeser explained.

Clinical slant

Sunday’s Plenary session at 11:00 a.m. will feature several top-rated abstracts, among them results of a phase III study on tocilizumab in giant cell arteritis to be presented by John Stone, MD. “Tocilizumab is a major breakthrough as a steroid-sparing treatment for the most common form of vasculitis that affects older adults,” Dr. Loeser said.

At 2:30 p.m. on Sunday at The Great Debate, Paul Emery, MD, and Arthur Kavanaugh, MD, will tackle the very important clinical topic of “To Taper or Not to Taper? – Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity.”

“People aren’t sure what to do. The fear with tapering is rebound, with the disease coming back even more forcefully. There is new evidence to suggest that tapering may be safe under certain circumstances. This session should inform attendees on how to make the decision to taper and on the best way to do it,” Dr. Loeser commented.

The Late-Breaking Abstract session on Tuesday at 4:30 p.m. will feature six clinical trials. Dr. Loeser singled out a study to be presented by Elaine Husni, MD, on “Vascular Safety of Celecoxib versus Ibuprofen or Naproxen” in more than 20,000 patients with osteoarthritis or rheumatoid arthritis.

“The fear is that COX-2 inhibitors have increased cardiovascular risk. The data from this study that will be presented at the meeting should answer the question of whether or not this is true in patients with arthritis,” Dr. Loeser explained.

Wednesday at 7:30 a.m. Candida Fratazzi, MD, will talk about “Emerging Biosimilars in Therapeutic Management,” a subject of great interest since they have the potential to be equally effective and less expensive than current biologics.

Two “bookends” of the meeting will frame the opening and closing. Sunday at 7:30 a.m., the “Year in Review” session will feature the best published studies on rheumatologic diseases from the past year, based on the judgment of two experts. Ingrid Lundberg, MD, will present the best clinical studies and Bruce Cronstein, MD, will present the best basic science studies. Wednesday at 7:30 a.m., John Cush, MD, and Dr. Kavanaugh will present the “Rheumatology Roundup” of the best abstracts and put them into context. “This session is usually quite entertaining,” Dr. Loeser said.

More sessions of clinical import

“In keeping with our meeting theme of fine-tuning our care of patients with rheumatic disease, I want to point out several sessions,” Dr. Gardner said.

Attendees interested in sessions on clinical applicability will have to choose between two different sessions Monday at 4:30 p.m.: one on dermatomyositis, a relatively rare but difficult-to-treat entity, and the other about treatment of the patient with rheumatoid arthritis when the patient is not well and suffering from comorbidities.

Monday at 8:30 a.m., an “Osteoporosis Update” will give listeners perspective on current and future therapies.

Sunday at 2:30 p.m., new guidelines for steroid-induced osteoporosis will be presented.

“Four or five sessions on the Tech Track will show rheumatologists how they can improve their practice by using technology,” Dr. Gardner said. “Several high-quality sessions are important to educators, including ‘Flipped Classroom, Technology, and Reflection’ [Monday at 12:30 p.m.] and ‘Year in Review’ [Sunday at 1:00 p.m.].”

Monday at 11:00 a.m., the Plenary session will feature Workforce Study results on how many rheumatologists will be needed in the year 2030, and in which geographic locations. This session will also include a discussion of the impact of part-time rheumatologists.

“Two sessions I am excited about are ‘Treat to Target in 2016,’ Tuesday at 4:30 p.m., and ‘Rheumatic Diseases in Native Americans,’ Sunday at 11:00 a.m.,” Dr. Gardner noted. “Concurrent abstract sessions throughout the meeting will feature discussions on new biologics, small molecules, and gene therapy.”

This year’s annual meeting of the American College of Rheumatology will feature cutting-edge research and results of studies that directly affect how attendees will manage patients once they are back in the clinical setting, according to both Richard Loeser, MD, program chair of the Annual Meeting Planning Committee (AMPC), and Gregory Gardner, MD, clinical subchair of the AMPC, who suggested special sessions of interest culled from the more than 450 sessions to be presented.

“It is an exciting time in rheumatology. Basic research is being translated into new therapies before our very eyes. Areas on the program this year that have translational potential include immunometabolism, blocking interleukin-1 (IL-1), T-cell receptor signaling, and meta-analysis of gene expression data. The meeting will also feature trials that refine and advance the management of rheumatologic diseases, including results on studies of new biologics,” Dr. Loeser said.

Hot sessions

Luke O’Neill, MD, will talk about immunometabolism Monday at 7:30 a.m. This session will explore a newly described connection between energy metabolism and the immune system and the link with inflammation.

Charles Dinarello, MD, will give the Philip Hensch Memorial Lecture Sunday at 8:30 a.m. on blocking IL-1 in inflammatory diseases. He will cover a host of diseases from gout to cancer, Dr. Loeser noted.

Another hot topic, T-cell receptor signaling in autoimmune diseases and the development of new therapies, will be discussed by Arthur Weiss, MD, Tuesday morning at 7:30 a.m.

Tuesday at 11:00 a.m., Peter Lipsky, MD, will tackle big data mining, presenting a meta-analysis of gene expression datasets to identify novel pathways and targets in systemic lupus erythematosus (SLE).

“SLE lags behind rheumatoid arthritis in therapeutic advances. A number of trials of biologics have failed in SLE, whereas they have been found effective in rheumatoid arthritis,” Dr. Loeser explained.

Clinical slant

Sunday’s Plenary session at 11:00 a.m. will feature several top-rated abstracts, among them results of a phase III study on tocilizumab in giant cell arteritis to be presented by John Stone, MD. “Tocilizumab is a major breakthrough as a steroid-sparing treatment for the most common form of vasculitis that affects older adults,” Dr. Loeser said.

At 2:30 p.m. on Sunday at The Great Debate, Paul Emery, MD, and Arthur Kavanaugh, MD, will tackle the very important clinical topic of “To Taper or Not to Taper? – Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity.”

“People aren’t sure what to do. The fear with tapering is rebound, with the disease coming back even more forcefully. There is new evidence to suggest that tapering may be safe under certain circumstances. This session should inform attendees on how to make the decision to taper and on the best way to do it,” Dr. Loeser commented.

The Late-Breaking Abstract session on Tuesday at 4:30 p.m. will feature six clinical trials. Dr. Loeser singled out a study to be presented by Elaine Husni, MD, on “Vascular Safety of Celecoxib versus Ibuprofen or Naproxen” in more than 20,000 patients with osteoarthritis or rheumatoid arthritis.

“The fear is that COX-2 inhibitors have increased cardiovascular risk. The data from this study that will be presented at the meeting should answer the question of whether or not this is true in patients with arthritis,” Dr. Loeser explained.

Wednesday at 7:30 a.m. Candida Fratazzi, MD, will talk about “Emerging Biosimilars in Therapeutic Management,” a subject of great interest since they have the potential to be equally effective and less expensive than current biologics.

Two “bookends” of the meeting will frame the opening and closing. Sunday at 7:30 a.m., the “Year in Review” session will feature the best published studies on rheumatologic diseases from the past year, based on the judgment of two experts. Ingrid Lundberg, MD, will present the best clinical studies and Bruce Cronstein, MD, will present the best basic science studies. Wednesday at 7:30 a.m., John Cush, MD, and Dr. Kavanaugh will present the “Rheumatology Roundup” of the best abstracts and put them into context. “This session is usually quite entertaining,” Dr. Loeser said.

More sessions of clinical import

“In keeping with our meeting theme of fine-tuning our care of patients with rheumatic disease, I want to point out several sessions,” Dr. Gardner said.

Attendees interested in sessions on clinical applicability will have to choose between two different sessions Monday at 4:30 p.m.: one on dermatomyositis, a relatively rare but difficult-to-treat entity, and the other about treatment of the patient with rheumatoid arthritis when the patient is not well and suffering from comorbidities.

Monday at 8:30 a.m., an “Osteoporosis Update” will give listeners perspective on current and future therapies.

Sunday at 2:30 p.m., new guidelines for steroid-induced osteoporosis will be presented.

“Four or five sessions on the Tech Track will show rheumatologists how they can improve their practice by using technology,” Dr. Gardner said. “Several high-quality sessions are important to educators, including ‘Flipped Classroom, Technology, and Reflection’ [Monday at 12:30 p.m.] and ‘Year in Review’ [Sunday at 1:00 p.m.].”

Monday at 11:00 a.m., the Plenary session will feature Workforce Study results on how many rheumatologists will be needed in the year 2030, and in which geographic locations. This session will also include a discussion of the impact of part-time rheumatologists.

“Two sessions I am excited about are ‘Treat to Target in 2016,’ Tuesday at 4:30 p.m., and ‘Rheumatic Diseases in Native Americans,’ Sunday at 11:00 a.m.,” Dr. Gardner noted. “Concurrent abstract sessions throughout the meeting will feature discussions on new biologics, small molecules, and gene therapy.”

Both dietary and supplemental calcium should be considered safe for the cardiovascular system as long as total intake doesn’t exceed 2,000-2,500 mg/day – the maximal tolerable level defined by the National Academy of Medicine, according to an updated Clinical Practice Guideline published online October 24 in Annals of Internal Medicine.

For generally healthy patients who don’t consume adequate calcium and take supplements, either alone or in combination with vitamin D, to prevent osteoporosis and related fractures, “discontinuation of supplemental calcium for safety reasons is not necessary and may be harmful to bone health,” said Stephen L. Kopecky, MD, of the Mayo Clinic, Rochester Minn., and his associates on the expert panel that wrote the new guideline.

Both dietary and supplemental calcium should be considered safe for the cardiovascular system as long as total intake doesn’t exceed 2,000-2,500 mg/day – the maximal tolerable level defined by the National Academy of Medicine, according to an updated Clinical Practice Guideline published online October 24 in Annals of Internal Medicine.

For generally healthy patients who don’t consume adequate calcium and take supplements, either alone or in combination with vitamin D, to prevent osteoporosis and related fractures, “discontinuation of supplemental calcium for safety reasons is not necessary and may be harmful to bone health,” said Stephen L. Kopecky, MD, of the Mayo Clinic, Rochester Minn., and his associates on the expert panel that wrote the new guideline.

Both dietary and supplemental calcium should be considered safe for the cardiovascular system as long as total intake doesn’t exceed 2,000-2,500 mg/day – the maximal tolerable level defined by the National Academy of Medicine, according to an updated Clinical Practice Guideline published online October 24 in Annals of Internal Medicine.

For generally healthy patients who don’t consume adequate calcium and take supplements, either alone or in combination with vitamin D, to prevent osteoporosis and related fractures, “discontinuation of supplemental calcium for safety reasons is not necessary and may be harmful to bone health,” said Stephen L. Kopecky, MD, of the Mayo Clinic, Rochester Minn., and his associates on the expert panel that wrote the new guideline.

The North American Menopause Society (NAMS) is affirming the safety and efficacy of hormone therapy for certain conditions, and in certain populations of menopausal women, in its soon-to-be released 2016 hormone therapy position statement.

An update from the society’s 2012 recommendations, the new statement will also give targeted recommendations for special populations of women to help guide clinicians in individualized treatment.

Special populations

Several special populations are addressed in the updated position statement. These include those who have reached early menopause because of primary ovarian insufficiency or because of oophorectomy. For these women, NAMS recommends hormone therapy until at least the median age of menopause. Making a level II recommendation, the NAMS committee wrote, “Observational studies suggest that benefits appear to outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.”

Other special populations for whom HT may be considered include women with a family history of breast cancer and women who are positive for the BRCA gene. Again turning to observational evidence, the NAMS committee makes a level II recommendation that “use of HT does not alter the risk for breast cancer in women with family history of breast cancer, although family history is one risk, among many, that should be assessed.”

BRCA-positive women who do not have breast cancer are at higher risk for primarily estrogen receptor–negative breast cancer. BRCA-positive women may have opted for elective oophorectomy, though, and the committee recommends considering the potential negative effects of estrogen depletion at a premenopausal age when weighing risks and benefits in surgically menopausal BRCA-positive patients. It’s appropriate to offer systemic HT until the median age of menopause in this population, if there are no contraindications, and after appropriate counseling, according to the position statement.

Individualized discussions about continuing HT beyond the median age of menopause are recommended, said Dr. Pinkerton. “We reviewed the literature and found no increased risk in observational studies of women with BRCA genes after oophorectomy who receive hormone therapy,” she said. “These decisions are best taken on an individual basis.” The recommendations for the BRCA population are also a level II recommendation.
 

Duration of use

Regarding extended use of HT, the NAMS statement breaks with the Beers criteria, saying that routine discontinuation of HT after the age of 65 years “is not supported by data.” These decisions, according to the new recommendations, should be individualized. This is a level III recommendation. Still, said Dr. Kaunitz, “many women grow out of their vasomotor symptoms,” and so an individualized approach might include indefinite use of low-dose vaginal estrogen therapy for GSM, he said.

The overall benefit-risk ratio for HT is also addressed in the position statement, which emphasizes an individualized approach that includes periodic reassessment of risk and benefit for particular patients. However, for patients younger than 60 years of age, or who are within 10 years of menopause, NAMS endorses an overall favorable risk-benefit profile for HT in two particular areas, barring contraindications. For this younger postmenopausal population, hormone therapy is beneficial for bothersome vasomotor symptoms, according to the position statement, and women with an increased risk of osteoporosis or fracture may also benefit from HT.

The benefit-risk profile may tip against HT for women who are starting hormone therapy more than 10 years after menopause, or when they are 60 years old or older, according to the statement. The authors cite elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

[email protected]

On Twitter @karioakes

The North American Menopause Society (NAMS) is affirming the safety and efficacy of hormone therapy for certain conditions, and in certain populations of menopausal women, in its soon-to-be released 2016 hormone therapy position statement.

An update from the society’s 2012 recommendations, the new statement will also give targeted recommendations for special populations of women to help guide clinicians in individualized treatment.

Special populations

Several special populations are addressed in the updated position statement. These include those who have reached early menopause because of primary ovarian insufficiency or because of oophorectomy. For these women, NAMS recommends hormone therapy until at least the median age of menopause. Making a level II recommendation, the NAMS committee wrote, “Observational studies suggest that benefits appear to outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.”

Other special populations for whom HT may be considered include women with a family history of breast cancer and women who are positive for the BRCA gene. Again turning to observational evidence, the NAMS committee makes a level II recommendation that “use of HT does not alter the risk for breast cancer in women with family history of breast cancer, although family history is one risk, among many, that should be assessed.”

BRCA-positive women who do not have breast cancer are at higher risk for primarily estrogen receptor–negative breast cancer. BRCA-positive women may have opted for elective oophorectomy, though, and the committee recommends considering the potential negative effects of estrogen depletion at a premenopausal age when weighing risks and benefits in surgically menopausal BRCA-positive patients. It’s appropriate to offer systemic HT until the median age of menopause in this population, if there are no contraindications, and after appropriate counseling, according to the position statement.

Individualized discussions about continuing HT beyond the median age of menopause are recommended, said Dr. Pinkerton. “We reviewed the literature and found no increased risk in observational studies of women with BRCA genes after oophorectomy who receive hormone therapy,” she said. “These decisions are best taken on an individual basis.” The recommendations for the BRCA population are also a level II recommendation.
 

Duration of use

Regarding extended use of HT, the NAMS statement breaks with the Beers criteria, saying that routine discontinuation of HT after the age of 65 years “is not supported by data.” These decisions, according to the new recommendations, should be individualized. This is a level III recommendation. Still, said Dr. Kaunitz, “many women grow out of their vasomotor symptoms,” and so an individualized approach might include indefinite use of low-dose vaginal estrogen therapy for GSM, he said.

The overall benefit-risk ratio for HT is also addressed in the position statement, which emphasizes an individualized approach that includes periodic reassessment of risk and benefit for particular patients. However, for patients younger than 60 years of age, or who are within 10 years of menopause, NAMS endorses an overall favorable risk-benefit profile for HT in two particular areas, barring contraindications. For this younger postmenopausal population, hormone therapy is beneficial for bothersome vasomotor symptoms, according to the position statement, and women with an increased risk of osteoporosis or fracture may also benefit from HT.

The benefit-risk profile may tip against HT for women who are starting hormone therapy more than 10 years after menopause, or when they are 60 years old or older, according to the statement. The authors cite elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

[email protected]

On Twitter @karioakes

The North American Menopause Society (NAMS) is affirming the safety and efficacy of hormone therapy for certain conditions, and in certain populations of menopausal women, in its soon-to-be released 2016 hormone therapy position statement.

An update from the society’s 2012 recommendations, the new statement will also give targeted recommendations for special populations of women to help guide clinicians in individualized treatment.

Special populations

Several special populations are addressed in the updated position statement. These include those who have reached early menopause because of primary ovarian insufficiency or because of oophorectomy. For these women, NAMS recommends hormone therapy until at least the median age of menopause. Making a level II recommendation, the NAMS committee wrote, “Observational studies suggest that benefits appear to outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.”

Other special populations for whom HT may be considered include women with a family history of breast cancer and women who are positive for the BRCA gene. Again turning to observational evidence, the NAMS committee makes a level II recommendation that “use of HT does not alter the risk for breast cancer in women with family history of breast cancer, although family history is one risk, among many, that should be assessed.”

BRCA-positive women who do not have breast cancer are at higher risk for primarily estrogen receptor–negative breast cancer. BRCA-positive women may have opted for elective oophorectomy, though, and the committee recommends considering the potential negative effects of estrogen depletion at a premenopausal age when weighing risks and benefits in surgically menopausal BRCA-positive patients. It’s appropriate to offer systemic HT until the median age of menopause in this population, if there are no contraindications, and after appropriate counseling, according to the position statement.

Individualized discussions about continuing HT beyond the median age of menopause are recommended, said Dr. Pinkerton. “We reviewed the literature and found no increased risk in observational studies of women with BRCA genes after oophorectomy who receive hormone therapy,” she said. “These decisions are best taken on an individual basis.” The recommendations for the BRCA population are also a level II recommendation.
 

Duration of use

Regarding extended use of HT, the NAMS statement breaks with the Beers criteria, saying that routine discontinuation of HT after the age of 65 years “is not supported by data.” These decisions, according to the new recommendations, should be individualized. This is a level III recommendation. Still, said Dr. Kaunitz, “many women grow out of their vasomotor symptoms,” and so an individualized approach might include indefinite use of low-dose vaginal estrogen therapy for GSM, he said.

The overall benefit-risk ratio for HT is also addressed in the position statement, which emphasizes an individualized approach that includes periodic reassessment of risk and benefit for particular patients. However, for patients younger than 60 years of age, or who are within 10 years of menopause, NAMS endorses an overall favorable risk-benefit profile for HT in two particular areas, barring contraindications. For this younger postmenopausal population, hormone therapy is beneficial for bothersome vasomotor symptoms, according to the position statement, and women with an increased risk of osteoporosis or fracture may also benefit from HT.

The benefit-risk profile may tip against HT for women who are starting hormone therapy more than 10 years after menopause, or when they are 60 years old or older, according to the statement. The authors cite elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

[email protected]

On Twitter @karioakes

The novel oral osteoporosis drug odanacatib significantly reduced fractures in postmenopausal women but was also associated with a significantly higher risk for stroke, according to data from a 5-year extension of a large phase III clinical trial.

Based on an independent analysis and verification of the risk for stroke, the drug’s sponsor, Merck, has withdrawn odanacatib from review by the Food and Drug Administration. “We are disappointed that the overall benefit-risk profile for odanacatib does not support filing or further development,” Roger M. Perlmutter, MD, president of Merck Research Laboratories, said in a statement.

[email protected]

On Twitter @karioakes

The novel oral osteoporosis drug odanacatib significantly reduced fractures in postmenopausal women but was also associated with a significantly higher risk for stroke, according to data from a 5-year extension of a large phase III clinical trial.

Based on an independent analysis and verification of the risk for stroke, the drug’s sponsor, Merck, has withdrawn odanacatib from review by the Food and Drug Administration. “We are disappointed that the overall benefit-risk profile for odanacatib does not support filing or further development,” Roger M. Perlmutter, MD, president of Merck Research Laboratories, said in a statement.

[email protected]

On Twitter @karioakes

The novel oral osteoporosis drug odanacatib significantly reduced fractures in postmenopausal women but was also associated with a significantly higher risk for stroke, according to data from a 5-year extension of a large phase III clinical trial.

Based on an independent analysis and verification of the risk for stroke, the drug’s sponsor, Merck, has withdrawn odanacatib from review by the Food and Drug Administration. “We are disappointed that the overall benefit-risk profile for odanacatib does not support filing or further development,” Roger M. Perlmutter, MD, president of Merck Research Laboratories, said in a statement.

[email protected]

On Twitter @karioakes

Administering 5 mg of zoledronic acid at the start of antiretroviral therapy to HIV-infected patients who have never previously undergone ART can significantly decrease the risk of bone density loss.

Those are the findings reported in a study of 63 viremic HIV patients, all of whom were aged 30 to 50 and had never undergone ART before. The participants were randomized into cohorts receiving either a single dose of 5 mg zoledronic acid or a placebo. ART consisted of atazanavir / ritonavir in combination with tenofovir / emtricitabine. “The skeletal effects of ART, though varied in magnitude, appear to be universal to all ART types including tenofovir alafenamide (TAF) containing and tenofovir disoproxil fumarate (TDF) sparing regimens,” according to the study, led by Ighovwerha Ofotokun, MD, of Emory University in Atlanta, and colleagues.

“We hypothesized that the preponderance of bone loss in this setting would occur during early period of therapy when T-cell recovery is most pronounced, providing an exploitable window for preemptive intervention to mitigate ART-induced bone resorption and preserve natural bone in this population,” the authors added.

Investigators performed plasma bone turnover markers and bone mineral density analyses at 0, 12, 24, and 48 weeks. Significant reductions in bone resorption was noted as early as 12 weeks after commencement, with a 73% reduction (P < .001); resorption reductions did not stay as robust but were similarly strong through 48 weeks (57%, P < .001).

C-terminal telopeptide of collagen (CTx) levels, the primary outcome, was not significantly different between the two cohorts at baseline: 0.154 nanograms per milliliter (ng/ml) for zoledronic acid vs. 0.190 ng/ml for placebo (P = 0.22). However, zoledronic acid was significantly lower than placebo at 12-, 24-, and 48-week follow-ups: 0.083 ng/ml vs. 0.305 ng/ml (P < .001) at 12 weeks, 0.117 ng/ml vs. 0.338 ng/ml (P < 0.001) at 24 weeks, and 0.116 ng/ml vs. 0.269 ng/ml, (P < 0.001) at 48 weeks. Additionally, higher improvements in lumbar spine, hip, and femoral BMD were noted in the zoledronic acid group at 12, 24, and 48 weeks, compared with the placebo group.

“[Zoledronic acid] at a single dose was safe and well tolerated, and resulted in comparable rate of virologic suppression and similar magnitude of CD4 T-cell reconstitution,” the authors concluded, adding that “these data define an optimal window for a pre-emptive intervention to forestall ART-induced bone loss and provide robust information needed to guide the design and implementation of larger confirmatory phase III, multicenter randomized clinical trials.”

The study was funded by the National Institute on Aging, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Ofotokun and other colleagues did not report relevant financial disclosures.

[email protected]

Administering 5 mg of zoledronic acid at the start of antiretroviral therapy to HIV-infected patients who have never previously undergone ART can significantly decrease the risk of bone density loss.

Those are the findings reported in a study of 63 viremic HIV patients, all of whom were aged 30 to 50 and had never undergone ART before. The participants were randomized into cohorts receiving either a single dose of 5 mg zoledronic acid or a placebo. ART consisted of atazanavir / ritonavir in combination with tenofovir / emtricitabine. “The skeletal effects of ART, though varied in magnitude, appear to be universal to all ART types including tenofovir alafenamide (TAF) containing and tenofovir disoproxil fumarate (TDF) sparing regimens,” according to the study, led by Ighovwerha Ofotokun, MD, of Emory University in Atlanta, and colleagues.

“We hypothesized that the preponderance of bone loss in this setting would occur during early period of therapy when T-cell recovery is most pronounced, providing an exploitable window for preemptive intervention to mitigate ART-induced bone resorption and preserve natural bone in this population,” the authors added.

Investigators performed plasma bone turnover markers and bone mineral density analyses at 0, 12, 24, and 48 weeks. Significant reductions in bone resorption was noted as early as 12 weeks after commencement, with a 73% reduction (P < .001); resorption reductions did not stay as robust but were similarly strong through 48 weeks (57%, P < .001).

C-terminal telopeptide of collagen (CTx) levels, the primary outcome, was not significantly different between the two cohorts at baseline: 0.154 nanograms per milliliter (ng/ml) for zoledronic acid vs. 0.190 ng/ml for placebo (P = 0.22). However, zoledronic acid was significantly lower than placebo at 12-, 24-, and 48-week follow-ups: 0.083 ng/ml vs. 0.305 ng/ml (P < .001) at 12 weeks, 0.117 ng/ml vs. 0.338 ng/ml (P < 0.001) at 24 weeks, and 0.116 ng/ml vs. 0.269 ng/ml, (P < 0.001) at 48 weeks. Additionally, higher improvements in lumbar spine, hip, and femoral BMD were noted in the zoledronic acid group at 12, 24, and 48 weeks, compared with the placebo group.

“[Zoledronic acid] at a single dose was safe and well tolerated, and resulted in comparable rate of virologic suppression and similar magnitude of CD4 T-cell reconstitution,” the authors concluded, adding that “these data define an optimal window for a pre-emptive intervention to forestall ART-induced bone loss and provide robust information needed to guide the design and implementation of larger confirmatory phase III, multicenter randomized clinical trials.”

The study was funded by the National Institute on Aging, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Ofotokun and other colleagues did not report relevant financial disclosures.

[email protected]

Administering 5 mg of zoledronic acid at the start of antiretroviral therapy to HIV-infected patients who have never previously undergone ART can significantly decrease the risk of bone density loss.

Those are the findings reported in a study of 63 viremic HIV patients, all of whom were aged 30 to 50 and had never undergone ART before. The participants were randomized into cohorts receiving either a single dose of 5 mg zoledronic acid or a placebo. ART consisted of atazanavir / ritonavir in combination with tenofovir / emtricitabine. “The skeletal effects of ART, though varied in magnitude, appear to be universal to all ART types including tenofovir alafenamide (TAF) containing and tenofovir disoproxil fumarate (TDF) sparing regimens,” according to the study, led by Ighovwerha Ofotokun, MD, of Emory University in Atlanta, and colleagues.

“We hypothesized that the preponderance of bone loss in this setting would occur during early period of therapy when T-cell recovery is most pronounced, providing an exploitable window for preemptive intervention to mitigate ART-induced bone resorption and preserve natural bone in this population,” the authors added.

Investigators performed plasma bone turnover markers and bone mineral density analyses at 0, 12, 24, and 48 weeks. Significant reductions in bone resorption was noted as early as 12 weeks after commencement, with a 73% reduction (P < .001); resorption reductions did not stay as robust but were similarly strong through 48 weeks (57%, P < .001).

C-terminal telopeptide of collagen (CTx) levels, the primary outcome, was not significantly different between the two cohorts at baseline: 0.154 nanograms per milliliter (ng/ml) for zoledronic acid vs. 0.190 ng/ml for placebo (P = 0.22). However, zoledronic acid was significantly lower than placebo at 12-, 24-, and 48-week follow-ups: 0.083 ng/ml vs. 0.305 ng/ml (P < .001) at 12 weeks, 0.117 ng/ml vs. 0.338 ng/ml (P < 0.001) at 24 weeks, and 0.116 ng/ml vs. 0.269 ng/ml, (P < 0.001) at 48 weeks. Additionally, higher improvements in lumbar spine, hip, and femoral BMD were noted in the zoledronic acid group at 12, 24, and 48 weeks, compared with the placebo group.

“[Zoledronic acid] at a single dose was safe and well tolerated, and resulted in comparable rate of virologic suppression and similar magnitude of CD4 T-cell reconstitution,” the authors concluded, adding that “these data define an optimal window for a pre-emptive intervention to forestall ART-induced bone loss and provide robust information needed to guide the design and implementation of larger confirmatory phase III, multicenter randomized clinical trials.”

The study was funded by the National Institute on Aging, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Ofotokun and other colleagues did not report relevant financial disclosures.

[email protected]

MIAMI – Diabetes mellitus, hypothyroidism, Cushing’s disease, and osteoporosis occur more frequently in people with psoriatic arthritis than in controls, a large cohort study reveals. Prevalence of these endocrine conditions was greater in a group of 3,161 patients with psoriatic arthritis, compared with 31,610 matched controls.

“We recommend that physicians should be aware of comorbid associations to provide comprehensive medical care to patients with psoriatic arthritis,” said Amir Haddad, MD, of the department of rheumatology at Carmel Medical Center in Haifa, Israel.

Dr. Haddad and his colleagues, however, found no significant differences in the prevalence of hyperthyroidism, hypo- and hyperparathyroidism, hyperprolactinemia, Addison’s disease, diabetes insipidus, pituitary adenoma, or acromegaly between groups in this retrospective, cross-sectional study.

They identified 1,474 men and 1,687 women diagnosed with psoriatic disease from 2000 to 2013 using the Clalit health services database in Israel. This group was a mean of 58 years old and 53% were women. Each patient was matched with 10 age- and gender-matched controls without psoriatic disease for the study.

“This is, to our knowledge, one of the largest real-life cohorts of psoriatic patient registries,” Dr. Haddad said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

In the psoriatic arthritis group versus controls, diabetes mellitus prevalence was 27.9% vs. 20.7%; for hypothyroidism it was 12.7% vs. 8.6%; and for Cushing’s disease it was 0.3% vs. 0.1%. All these differences were statically significant (P less than 0.0001). Osteoporosis prevalence also differed significantly between the psoriatic arthritis and control groups: 13.2% vs. 9.1% (P less than 0.001).

Greater awareness of nonskin and nonjoint comorbidities is important, Dr. Haddad said, because it can influence choice of therapy and management of patients with psoriatic arthritis.

The investigators also conducted univariate and multivariate regression analyses. Compared with controls, the results suggest psoriatic arthritis patients have a higher risk for diabetes mellitus (odds ratio, 1.48), hypothyroidism (OR, 1.56), and osteoporosis (OR, 1.52). The risk for Cushing’s disease was notably higher (OR, 5.31) in the univariate analysis.

Risks for these endocrine conditions remained higher for the psoriatic arthritis patients in a multivariate regression analysis as well. For example, risk for diabetes mellitus (OR, 1.30) remained after adjusting for age, gender, smoking, obesity, and steroid use. Risk of hypothyroidism (OR, 1.61) remained after adjusting for age and gender; risk of osteoporosis (OR, 1.50) after adjusting for age, gender, steroid use, and smoking; and risk of Cushing’s disease (OR, 3.79) after adjustment for age, gender, and steroid use.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

MIAMI – Diabetes mellitus, hypothyroidism, Cushing’s disease, and osteoporosis occur more frequently in people with psoriatic arthritis than in controls, a large cohort study reveals. Prevalence of these endocrine conditions was greater in a group of 3,161 patients with psoriatic arthritis, compared with 31,610 matched controls.

“We recommend that physicians should be aware of comorbid associations to provide comprehensive medical care to patients with psoriatic arthritis,” said Amir Haddad, MD, of the department of rheumatology at Carmel Medical Center in Haifa, Israel.

Dr. Haddad and his colleagues, however, found no significant differences in the prevalence of hyperthyroidism, hypo- and hyperparathyroidism, hyperprolactinemia, Addison’s disease, diabetes insipidus, pituitary adenoma, or acromegaly between groups in this retrospective, cross-sectional study.

They identified 1,474 men and 1,687 women diagnosed with psoriatic disease from 2000 to 2013 using the Clalit health services database in Israel. This group was a mean of 58 years old and 53% were women. Each patient was matched with 10 age- and gender-matched controls without psoriatic disease for the study.

“This is, to our knowledge, one of the largest real-life cohorts of psoriatic patient registries,” Dr. Haddad said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

In the psoriatic arthritis group versus controls, diabetes mellitus prevalence was 27.9% vs. 20.7%; for hypothyroidism it was 12.7% vs. 8.6%; and for Cushing’s disease it was 0.3% vs. 0.1%. All these differences were statically significant (P less than 0.0001). Osteoporosis prevalence also differed significantly between the psoriatic arthritis and control groups: 13.2% vs. 9.1% (P less than 0.001).

Greater awareness of nonskin and nonjoint comorbidities is important, Dr. Haddad said, because it can influence choice of therapy and management of patients with psoriatic arthritis.

The investigators also conducted univariate and multivariate regression analyses. Compared with controls, the results suggest psoriatic arthritis patients have a higher risk for diabetes mellitus (odds ratio, 1.48), hypothyroidism (OR, 1.56), and osteoporosis (OR, 1.52). The risk for Cushing’s disease was notably higher (OR, 5.31) in the univariate analysis.

Risks for these endocrine conditions remained higher for the psoriatic arthritis patients in a multivariate regression analysis as well. For example, risk for diabetes mellitus (OR, 1.30) remained after adjusting for age, gender, smoking, obesity, and steroid use. Risk of hypothyroidism (OR, 1.61) remained after adjusting for age and gender; risk of osteoporosis (OR, 1.50) after adjusting for age, gender, steroid use, and smoking; and risk of Cushing’s disease (OR, 3.79) after adjustment for age, gender, and steroid use.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

MIAMI – Diabetes mellitus, hypothyroidism, Cushing’s disease, and osteoporosis occur more frequently in people with psoriatic arthritis than in controls, a large cohort study reveals. Prevalence of these endocrine conditions was greater in a group of 3,161 patients with psoriatic arthritis, compared with 31,610 matched controls.

“We recommend that physicians should be aware of comorbid associations to provide comprehensive medical care to patients with psoriatic arthritis,” said Amir Haddad, MD, of the department of rheumatology at Carmel Medical Center in Haifa, Israel.

Dr. Haddad and his colleagues, however, found no significant differences in the prevalence of hyperthyroidism, hypo- and hyperparathyroidism, hyperprolactinemia, Addison’s disease, diabetes insipidus, pituitary adenoma, or acromegaly between groups in this retrospective, cross-sectional study.

They identified 1,474 men and 1,687 women diagnosed with psoriatic disease from 2000 to 2013 using the Clalit health services database in Israel. This group was a mean of 58 years old and 53% were women. Each patient was matched with 10 age- and gender-matched controls without psoriatic disease for the study.

“This is, to our knowledge, one of the largest real-life cohorts of psoriatic patient registries,” Dr. Haddad said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

In the psoriatic arthritis group versus controls, diabetes mellitus prevalence was 27.9% vs. 20.7%; for hypothyroidism it was 12.7% vs. 8.6%; and for Cushing’s disease it was 0.3% vs. 0.1%. All these differences were statically significant (P less than 0.0001). Osteoporosis prevalence also differed significantly between the psoriatic arthritis and control groups: 13.2% vs. 9.1% (P less than 0.001).

Greater awareness of nonskin and nonjoint comorbidities is important, Dr. Haddad said, because it can influence choice of therapy and management of patients with psoriatic arthritis.

The investigators also conducted univariate and multivariate regression analyses. Compared with controls, the results suggest psoriatic arthritis patients have a higher risk for diabetes mellitus (odds ratio, 1.48), hypothyroidism (OR, 1.56), and osteoporosis (OR, 1.52). The risk for Cushing’s disease was notably higher (OR, 5.31) in the univariate analysis.

Risks for these endocrine conditions remained higher for the psoriatic arthritis patients in a multivariate regression analysis as well. For example, risk for diabetes mellitus (OR, 1.30) remained after adjusting for age, gender, smoking, obesity, and steroid use. Risk of hypothyroidism (OR, 1.61) remained after adjusting for age and gender; risk of osteoporosis (OR, 1.50) after adjusting for age, gender, steroid use, and smoking; and risk of Cushing’s disease (OR, 3.79) after adjustment for age, gender, and steroid use.

The large, population-based cohort is a strength of the study. “We are now going back to see how many of these patients were seen by rheumatologists,” Dr. Haddad said. A lack of association with disease burden is a potential limitation, he added.

Thirty percent of patients were treated with biologics and about 67% with steroids. “That number treated with steroids seems high,” a meeting attendee commented. Dr. Haddad explained that it is the percentage ever treated with steroids, not necessarily currently on steroids.

In a separate session at the GRAPPA meeting addressing psoriatic disease treatment recommendations, an attendee asked about specific recommendations for comorbidities. For now, GRAPPA plans to include comorbidities within its overall recommendations, as it did in its most recent update, released in January 2016. A limited amount of data is a primary reason.

“As the evidence on comorbidities gets better, we may someday have separate recommendations for comorbidities,” said Laura Coates, MD, a clinical lecturer in rheumatology at the University of Leeds (England).

“The comorbidities are very important,” said Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego. “That’s trickier and deals with the international nature of GRAPPA. It’s hard to say, ‘Go see this specialist,’ because that might not be standard of care in that country.”

Dr. Haddad, Dr. Coates, and Dr. Kavanaugh reported having no relevant financial disclosures.

LONDON – The European League Against Rheumatism and the European Federation of National Associations of Orthopaedics and Traumatology have joined forces to develop recommendations for the prevention and management of fragility fractures.

Such fractures are common in men and women over the age of 50 years and can lead to repeat fracture in some patients. The recommendations are unique as they are the first to consider both acute orthopedic and postfracture rheumatologic care, said Willem F. Lems, MD, PhD, of the Amsterdam Rheumatology and Immunology Centre.

At the European Congress of Rheumatology, Dr. Lems provided an overview of the draft recommendations, noting that there would be several overarching principles, one of which recognized the multidisciplinary nature of caring for someone with a fragility fracture. An important point is not who is taking care of the patient, but that the patient is given the best possible care within the multidisciplinary framework.

Wikimedia Commons/Sjoehest/ CC BY-llSA 3.0

What constitutes optimal care of course depends on the clinical situation, notably the type of fracture and the age of the patient, and optimal care in all phases of presentation (pre-, peri- and postoperative) can have an important effect on a patient’s outcome. The prevention of subsequent fractures is a key focus, with the recommendation that all patients should be investigated systematically and those deemed at high risk for another fracture should be prescribed both pharmacologic and nonpharmacologic interventions as appropriate. Patient education is also considered important.

As for all EULAR-developed recommendations, standard procedures were followed that involved convening an expert scientific advisory committee and using the Delphi technique to come up with the most important research questions that would be used to formulate the final 10 recommendations. Four of the recommendations cover the acute care setting and six provide advice on postfracture care.

The first of the acute care recommendations looks at pre- and perioperative management of a fragility fracture and highlights that, within 24-48 hours of admission, patients should receive adequate pain and fluid management and treatment, including early surgery if appropriate. This is based on evidence that better outcomes can be achieved in terms of both morbidity and mortality if patients can be seen and managed quickly.

Another of the acute care recommendations focuses on orthogeriatric care, noting that the orthopedic surgeon and a dedicated orthogeriatric team should work together, particularly for elderly patients who have suffered a hip fracture. Key elements here are the management of and prevention of delirium, deep vein thrombosis, pressure sores, and malnutrition.

As for actual fracture treatment, a balanced approach is advised when deciding upon a surgical or nonsurgical approach, especially because this is likely to be an older population with other comorbidities. Only one in three vertebral fractures are symptomatic and only about 10% of patients will be hospitalized for pain. Analgesics, modifying activities, and bracing can be options here. Surgical options for distal radial fracture, hip fracture, and trochanteric and femoral neck fractures are included.

The fourth recommendation looks at the organization of postfracture care and the need for a systematic approach to identify those who may be at risk for subsequent fractures, starting with the suggestion that any patient older than 50 years with a recent fracture should be assessed. The fifth recommendation addresses ways to evaluate this risk, such as looking at the clinical risk factors, performing bone scans and imaging, and screening for underlying osteoporosis or metabolic disorders.

Implementation is the next step, and the sixth recommendation suggests ways these recommendations could be integrated into routine practice. Often one of the biggest barriers to effective postfracture care is the lack of patient, and sometimes clinician, awareness of the risk for a subsequent fracture. This recommendation looks at the role of a possible local fracture liaison service or facilitator to coordinate between the various members of the multidisciplinary team from secondary (orthopedic surgeons, rheumatologists, endocrinologists, and geriatricians) to primary care.

The seventh recommendation addresses rehabilitation and the need to initiate physical training and muscle strengthening as early as possible after the initial fracture, with long-term continuation of balance training and fall prevention.

The final three recommendations focus on how to educate patients about their risk factors, need for follow-up, and the duration of any pharmacologic or nonpharmacologic therapy that they may need. Nonpharmacologic options might include stopping smoking, limiting alcohol intake, as well as taking supplements such as calcium or vitamin D. There will be specific guidance on the use of calcium and vitamin D, which have both pros and cons, but the optimal dosage appears to be 1,000–1,200 mg/day for calcium and 800 IU/day for vitamin D.

Pharmacologic options to prevent subsequent fragility fractures include the bisphosphonates alendronate, risedronate, and zoledronic acid (Reclast), and also the monoclonal antibody denosumab (Prolia). These are the only drugs that have been shown to reduced the risk for vertebral, nonvertebral, and hip fractures in primary analyses. Adherence, tolerance, and regular monitoring are key, and a five-step plan is suggested to aid clinical decision making that covers case finding, risk evaluation, differential diagnosis, treatment, and follow-up.

The recommendations are being finalized and should be available for publication later this year. The recommendations task force also plans to propose a research agenda.

Dr. Lems had no relevant disclosures.

LONDON – The European League Against Rheumatism and the European Federation of National Associations of Orthopaedics and Traumatology have joined forces to develop recommendations for the prevention and management of fragility fractures.

Such fractures are common in men and women over the age of 50 years and can lead to repeat fracture in some patients. The recommendations are unique as they are the first to consider both acute orthopedic and postfracture rheumatologic care, said Willem F. Lems, MD, PhD, of the Amsterdam Rheumatology and Immunology Centre.

At the European Congress of Rheumatology, Dr. Lems provided an overview of the draft recommendations, noting that there would be several overarching principles, one of which recognized the multidisciplinary nature of caring for someone with a fragility fracture. An important point is not who is taking care of the patient, but that the patient is given the best possible care within the multidisciplinary framework.

Wikimedia Commons/Sjoehest/ CC BY-llSA 3.0

What constitutes optimal care of course depends on the clinical situation, notably the type of fracture and the age of the patient, and optimal care in all phases of presentation (pre-, peri- and postoperative) can have an important effect on a patient’s outcome. The prevention of subsequent fractures is a key focus, with the recommendation that all patients should be investigated systematically and those deemed at high risk for another fracture should be prescribed both pharmacologic and nonpharmacologic interventions as appropriate. Patient education is also considered important.

As for all EULAR-developed recommendations, standard procedures were followed that involved convening an expert scientific advisory committee and using the Delphi technique to come up with the most important research questions that would be used to formulate the final 10 recommendations. Four of the recommendations cover the acute care setting and six provide advice on postfracture care.

The first of the acute care recommendations looks at pre- and perioperative management of a fragility fracture and highlights that, within 24-48 hours of admission, patients should receive adequate pain and fluid management and treatment, including early surgery if appropriate. This is based on evidence that better outcomes can be achieved in terms of both morbidity and mortality if patients can be seen and managed quickly.

Another of the acute care recommendations focuses on orthogeriatric care, noting that the orthopedic surgeon and a dedicated orthogeriatric team should work together, particularly for elderly patients who have suffered a hip fracture. Key elements here are the management of and prevention of delirium, deep vein thrombosis, pressure sores, and malnutrition.

As for actual fracture treatment, a balanced approach is advised when deciding upon a surgical or nonsurgical approach, especially because this is likely to be an older population with other comorbidities. Only one in three vertebral fractures are symptomatic and only about 10% of patients will be hospitalized for pain. Analgesics, modifying activities, and bracing can be options here. Surgical options for distal radial fracture, hip fracture, and trochanteric and femoral neck fractures are included.

The fourth recommendation looks at the organization of postfracture care and the need for a systematic approach to identify those who may be at risk for subsequent fractures, starting with the suggestion that any patient older than 50 years with a recent fracture should be assessed. The fifth recommendation addresses ways to evaluate this risk, such as looking at the clinical risk factors, performing bone scans and imaging, and screening for underlying osteoporosis or metabolic disorders.

Implementation is the next step, and the sixth recommendation suggests ways these recommendations could be integrated into routine practice. Often one of the biggest barriers to effective postfracture care is the lack of patient, and sometimes clinician, awareness of the risk for a subsequent fracture. This recommendation looks at the role of a possible local fracture liaison service or facilitator to coordinate between the various members of the multidisciplinary team from secondary (orthopedic surgeons, rheumatologists, endocrinologists, and geriatricians) to primary care.

The seventh recommendation addresses rehabilitation and the need to initiate physical training and muscle strengthening as early as possible after the initial fracture, with long-term continuation of balance training and fall prevention.

The final three recommendations focus on how to educate patients about their risk factors, need for follow-up, and the duration of any pharmacologic or nonpharmacologic therapy that they may need. Nonpharmacologic options might include stopping smoking, limiting alcohol intake, as well as taking supplements such as calcium or vitamin D. There will be specific guidance on the use of calcium and vitamin D, which have both pros and cons, but the optimal dosage appears to be 1,000–1,200 mg/day for calcium and 800 IU/day for vitamin D.

Pharmacologic options to prevent subsequent fragility fractures include the bisphosphonates alendronate, risedronate, and zoledronic acid (Reclast), and also the monoclonal antibody denosumab (Prolia). These are the only drugs that have been shown to reduced the risk for vertebral, nonvertebral, and hip fractures in primary analyses. Adherence, tolerance, and regular monitoring are key, and a five-step plan is suggested to aid clinical decision making that covers case finding, risk evaluation, differential diagnosis, treatment, and follow-up.

The recommendations are being finalized and should be available for publication later this year. The recommendations task force also plans to propose a research agenda.

Dr. Lems had no relevant disclosures.

LONDON – The European League Against Rheumatism and the European Federation of National Associations of Orthopaedics and Traumatology have joined forces to develop recommendations for the prevention and management of fragility fractures.

Such fractures are common in men and women over the age of 50 years and can lead to repeat fracture in some patients. The recommendations are unique as they are the first to consider both acute orthopedic and postfracture rheumatologic care, said Willem F. Lems, MD, PhD, of the Amsterdam Rheumatology and Immunology Centre.

At the European Congress of Rheumatology, Dr. Lems provided an overview of the draft recommendations, noting that there would be several overarching principles, one of which recognized the multidisciplinary nature of caring for someone with a fragility fracture. An important point is not who is taking care of the patient, but that the patient is given the best possible care within the multidisciplinary framework.

Wikimedia Commons/Sjoehest/ CC BY-llSA 3.0

What constitutes optimal care of course depends on the clinical situation, notably the type of fracture and the age of the patient, and optimal care in all phases of presentation (pre-, peri- and postoperative) can have an important effect on a patient’s outcome. The prevention of subsequent fractures is a key focus, with the recommendation that all patients should be investigated systematically and those deemed at high risk for another fracture should be prescribed both pharmacologic and nonpharmacologic interventions as appropriate. Patient education is also considered important.

As for all EULAR-developed recommendations, standard procedures were followed that involved convening an expert scientific advisory committee and using the Delphi technique to come up with the most important research questions that would be used to formulate the final 10 recommendations. Four of the recommendations cover the acute care setting and six provide advice on postfracture care.

The first of the acute care recommendations looks at pre- and perioperative management of a fragility fracture and highlights that, within 24-48 hours of admission, patients should receive adequate pain and fluid management and treatment, including early surgery if appropriate. This is based on evidence that better outcomes can be achieved in terms of both morbidity and mortality if patients can be seen and managed quickly.

Another of the acute care recommendations focuses on orthogeriatric care, noting that the orthopedic surgeon and a dedicated orthogeriatric team should work together, particularly for elderly patients who have suffered a hip fracture. Key elements here are the management of and prevention of delirium, deep vein thrombosis, pressure sores, and malnutrition.

As for actual fracture treatment, a balanced approach is advised when deciding upon a surgical or nonsurgical approach, especially because this is likely to be an older population with other comorbidities. Only one in three vertebral fractures are symptomatic and only about 10% of patients will be hospitalized for pain. Analgesics, modifying activities, and bracing can be options here. Surgical options for distal radial fracture, hip fracture, and trochanteric and femoral neck fractures are included.

The fourth recommendation looks at the organization of postfracture care and the need for a systematic approach to identify those who may be at risk for subsequent fractures, starting with the suggestion that any patient older than 50 years with a recent fracture should be assessed. The fifth recommendation addresses ways to evaluate this risk, such as looking at the clinical risk factors, performing bone scans and imaging, and screening for underlying osteoporosis or metabolic disorders.

Implementation is the next step, and the sixth recommendation suggests ways these recommendations could be integrated into routine practice. Often one of the biggest barriers to effective postfracture care is the lack of patient, and sometimes clinician, awareness of the risk for a subsequent fracture. This recommendation looks at the role of a possible local fracture liaison service or facilitator to coordinate between the various members of the multidisciplinary team from secondary (orthopedic surgeons, rheumatologists, endocrinologists, and geriatricians) to primary care.

The seventh recommendation addresses rehabilitation and the need to initiate physical training and muscle strengthening as early as possible after the initial fracture, with long-term continuation of balance training and fall prevention.

The final three recommendations focus on how to educate patients about their risk factors, need for follow-up, and the duration of any pharmacologic or nonpharmacologic therapy that they may need. Nonpharmacologic options might include stopping smoking, limiting alcohol intake, as well as taking supplements such as calcium or vitamin D. There will be specific guidance on the use of calcium and vitamin D, which have both pros and cons, but the optimal dosage appears to be 1,000–1,200 mg/day for calcium and 800 IU/day for vitamin D.

Pharmacologic options to prevent subsequent fragility fractures include the bisphosphonates alendronate, risedronate, and zoledronic acid (Reclast), and also the monoclonal antibody denosumab (Prolia). These are the only drugs that have been shown to reduced the risk for vertebral, nonvertebral, and hip fractures in primary analyses. Adherence, tolerance, and regular monitoring are key, and a five-step plan is suggested to aid clinical decision making that covers case finding, risk evaluation, differential diagnosis, treatment, and follow-up.

The recommendations are being finalized and should be available for publication later this year. The recommendations task force also plans to propose a research agenda.

Dr. Lems had no relevant disclosures.

LONDON – One of the largest studies of pregnancy outcomes after bisphosphonate exposure has found no evidence for major teratogenic effects in women with inflammatory diseases and glucocorticoid-induced osteoporosis and women with bone diseases.

However, the investigators for the French case-control study did find higher rates of neonatal complications and spontaneous abortion among infants of mothers with systemic inflammatory diseases and bisphosphonate use, but the results could be the result of confounding because of the severity of underlying disease and exposure to other medications.

“I think if a women is worried about bisphosphonate exposure during pregnancy, this study can bring her some reassuring news,” although it does not necessarily mean that bisphosphonates are safe during pregnancy, first author Aurélien Sokal said in an interview at the European Congress of Rheumatology. He is a medical student at Beaujon Hospital, Clichy, France, but conducted the study with colleagues during his time in training in the rheumatology department at Paris-Sud University.

“Very little is known about the effect of bisphosphonates on pregnancy outcomes and fetal development,” Mr. Sokal said, and they are feared for possible teratogenic effects in pregnancy because of their long half-life in bone – where they can be released even 1 year after their administration – as well as their ability to cross the placenta and high affinity for high-turnover bones, such as those in a growing fetus. He also noted that abnormalities in bone length, low birth weights, and bone diseases have been observed in rats exposed to bisphosphonates during gestation.

The study compared 23 patients with inflammatory diseases and bisphosphonate exposure during pregnancy against 92 controls with inflammatory diseases but no exposure, and 16 with bone diseases and exposure to bisphosphonates against 64 healthy controls with no underlying disease or bisphosphonate use. The patients came from a database assembled by the French Reference Center of Teratogenic Agents (CRAT) in Paris that has collected information since 1975 on patients referred for any drug exposure during pregnancy and followed their care through the end of pregnancy. The 39 patients who were exposed to bisphosphonates took the drugs during 1987-2014 within the 6 weeks preceding (n = 6) or during pregnancy (n = 33). They had a mean age of 33 years.

Systemic inflammatory diseases

The systemic inflammatory diseases found in women in the study included systemic lupus erythematosus (SLE), rheumatoid arthritis, antiphospholipid syndrome, systemic vasculitis, and other diseases. Of the 23 cases with systemic inflammatory diseases, 16 took risedronate, 5 took alendronate, 1 took etidronate, and the bisphosphonate was unknown in 1. Bisphosphonate exposure occurred before pregnancy in 2, during the first trimester in 21, second trimester in 4, third trimester in 4, and in all trimesters in 1.

Other types of medications were used significantly more often by patients with systemic inflammatory diseases than by controls: steroids (78% vs. 47%), methotrexate (26% vs. 5%), colchicine (17% vs. 2%), proton pump inhibitors (22% vs. 5%), and reproductive hormones (17% vs. 2%). Controls took antimalarials significantly more often (50% vs. 22%).

Voluntary abortions occurred at a similar rate in both exposed and unexposed women (12% vs. 9%), whereas significantly more therapeutic pregnancy terminations occurred among women exposed to bisphosphonates (17% vs. 1%). Live births occurred in 94% of the remaining exposed pregnant women, compared with 80% of controls.

Newborns were delivered at a mean of 38 weeks in both cases and controls, and there were no differences in birth weight, length, or rate of congenital malformation (9% vs. 2%).

The two malformations in neonates from exposed women had an uncertain link to bisphosphonates. One involved a neonate with severe malformative syndrome and advanced bone maturation who had a mother with SLE and was exposed to multiple drugs, including mycophenolate mofetil. The other neonate had ductus arteriosus, inguinal hernia, and negative otoacoustic emission; the baby’s mother had Crohn’s disease but had not taken known teratogenic drugs.

Two neonatal malformations among control women involved one neonate with severe malformative syndrome who had a mother with SLE but who was without exposure to known teratogenic drugs, and another with convulsant encephalopathy whose mother had systemic sclerosis and took pentoxifylline, cisapride, dihydroergocryptine, and colchicine.

However, cases had a 25% rate of neonatal complications, compared with a significantly lower 5% in controls. No infants had hypocalcemia.

Bone diseases

The 16 women with bone diseases included 9 with osteoporosis, 3 with malignancy, and 4 with miscellaneous bone conditions. A total of 5 received intravenous bisphosphonates and 11 received oral drugs (9 alendronate, 2 other). Most received a bisphosphonate in the first trimester (9 patients), but also 4 received it before pregnancy and 3 in the second trimester. More pregnancy terminations (voluntary or therapeutic) occurred among women with bone disease when compared with controls (19% vs. 3%), but the difference was not statistically significant. However in the remaining patients, live births occurred significantly less often in cases than in controls (69% vs. 100%). Birth weight, length, gestational age at birth, and the rates of congenital malformation and neonatal complications were otherwise similar.

The results of the study fall in line with those from the two major previous controlled studies on 24 women (Reprod Toxicol. 2006 Nov;22:578-9) and 21 women (Bone. 2009 Mar;44:428-30). Another series of 10 bisphosphonate-exposed pregnancies described 2 malformations, including 1 ventricular septal defect and 1 kidney and cardiac malformation (Autoimmun Rev. 2010 Jun;9:547-52). Another single case report described a neonate with bilateral talipes equinovarus (J Bone Miner Res. 2004 Oct;19:1742-5). A literature review of 78 cases of bisphosphonate exposure during or prior to pregnancy reported three malformations (Hormones [Athens]. 2011 Oct-Dec;10:280-91).

The study is ongoing and continues to collect data on the follow-up of children, Mr. Sokal said.

The study had no specific funding, and none of the investigators had disclosures to report.

[email protected]

LONDON – One of the largest studies of pregnancy outcomes after bisphosphonate exposure has found no evidence for major teratogenic effects in women with inflammatory diseases and glucocorticoid-induced osteoporosis and women with bone diseases.

However, the investigators for the French case-control study did find higher rates of neonatal complications and spontaneous abortion among infants of mothers with systemic inflammatory diseases and bisphosphonate use, but the results could be the result of confounding because of the severity of underlying disease and exposure to other medications.

“I think if a women is worried about bisphosphonate exposure during pregnancy, this study can bring her some reassuring news,” although it does not necessarily mean that bisphosphonates are safe during pregnancy, first author Aurélien Sokal said in an interview at the European Congress of Rheumatology. He is a medical student at Beaujon Hospital, Clichy, France, but conducted the study with colleagues during his time in training in the rheumatology department at Paris-Sud University.

“Very little is known about the effect of bisphosphonates on pregnancy outcomes and fetal development,” Mr. Sokal said, and they are feared for possible teratogenic effects in pregnancy because of their long half-life in bone – where they can be released even 1 year after their administration – as well as their ability to cross the placenta and high affinity for high-turnover bones, such as those in a growing fetus. He also noted that abnormalities in bone length, low birth weights, and bone diseases have been observed in rats exposed to bisphosphonates during gestation.

The study compared 23 patients with inflammatory diseases and bisphosphonate exposure during pregnancy against 92 controls with inflammatory diseases but no exposure, and 16 with bone diseases and exposure to bisphosphonates against 64 healthy controls with no underlying disease or bisphosphonate use. The patients came from a database assembled by the French Reference Center of Teratogenic Agents (CRAT) in Paris that has collected information since 1975 on patients referred for any drug exposure during pregnancy and followed their care through the end of pregnancy. The 39 patients who were exposed to bisphosphonates took the drugs during 1987-2014 within the 6 weeks preceding (n = 6) or during pregnancy (n = 33). They had a mean age of 33 years.

Systemic inflammatory diseases

The systemic inflammatory diseases found in women in the study included systemic lupus erythematosus (SLE), rheumatoid arthritis, antiphospholipid syndrome, systemic vasculitis, and other diseases. Of the 23 cases with systemic inflammatory diseases, 16 took risedronate, 5 took alendronate, 1 took etidronate, and the bisphosphonate was unknown in 1. Bisphosphonate exposure occurred before pregnancy in 2, during the first trimester in 21, second trimester in 4, third trimester in 4, and in all trimesters in 1.

Other types of medications were used significantly more often by patients with systemic inflammatory diseases than by controls: steroids (78% vs. 47%), methotrexate (26% vs. 5%), colchicine (17% vs. 2%), proton pump inhibitors (22% vs. 5%), and reproductive hormones (17% vs. 2%). Controls took antimalarials significantly more often (50% vs. 22%).

Voluntary abortions occurred at a similar rate in both exposed and unexposed women (12% vs. 9%), whereas significantly more therapeutic pregnancy terminations occurred among women exposed to bisphosphonates (17% vs. 1%). Live births occurred in 94% of the remaining exposed pregnant women, compared with 80% of controls.

Newborns were delivered at a mean of 38 weeks in both cases and controls, and there were no differences in birth weight, length, or rate of congenital malformation (9% vs. 2%).

The two malformations in neonates from exposed women had an uncertain link to bisphosphonates. One involved a neonate with severe malformative syndrome and advanced bone maturation who had a mother with SLE and was exposed to multiple drugs, including mycophenolate mofetil. The other neonate had ductus arteriosus, inguinal hernia, and negative otoacoustic emission; the baby’s mother had Crohn’s disease but had not taken known teratogenic drugs.

Two neonatal malformations among control women involved one neonate with severe malformative syndrome who had a mother with SLE but who was without exposure to known teratogenic drugs, and another with convulsant encephalopathy whose mother had systemic sclerosis and took pentoxifylline, cisapride, dihydroergocryptine, and colchicine.

However, cases had a 25% rate of neonatal complications, compared with a significantly lower 5% in controls. No infants had hypocalcemia.

Bone diseases

The 16 women with bone diseases included 9 with osteoporosis, 3 with malignancy, and 4 with miscellaneous bone conditions. A total of 5 received intravenous bisphosphonates and 11 received oral drugs (9 alendronate, 2 other). Most received a bisphosphonate in the first trimester (9 patients), but also 4 received it before pregnancy and 3 in the second trimester. More pregnancy terminations (voluntary or therapeutic) occurred among women with bone disease when compared with controls (19% vs. 3%), but the difference was not statistically significant. However in the remaining patients, live births occurred significantly less often in cases than in controls (69% vs. 100%). Birth weight, length, gestational age at birth, and the rates of congenital malformation and neonatal complications were otherwise similar.

The results of the study fall in line with those from the two major previous controlled studies on 24 women (Reprod Toxicol. 2006 Nov;22:578-9) and 21 women (Bone. 2009 Mar;44:428-30). Another series of 10 bisphosphonate-exposed pregnancies described 2 malformations, including 1 ventricular septal defect and 1 kidney and cardiac malformation (Autoimmun Rev. 2010 Jun;9:547-52). Another single case report described a neonate with bilateral talipes equinovarus (J Bone Miner Res. 2004 Oct;19:1742-5). A literature review of 78 cases of bisphosphonate exposure during or prior to pregnancy reported three malformations (Hormones [Athens]. 2011 Oct-Dec;10:280-91).

The study is ongoing and continues to collect data on the follow-up of children, Mr. Sokal said.

The study had no specific funding, and none of the investigators had disclosures to report.

[email protected]

LONDON – One of the largest studies of pregnancy outcomes after bisphosphonate exposure has found no evidence for major teratogenic effects in women with inflammatory diseases and glucocorticoid-induced osteoporosis and women with bone diseases.

However, the investigators for the French case-control study did find higher rates of neonatal complications and spontaneous abortion among infants of mothers with systemic inflammatory diseases and bisphosphonate use, but the results could be the result of confounding because of the severity of underlying disease and exposure to other medications.

“I think if a women is worried about bisphosphonate exposure during pregnancy, this study can bring her some reassuring news,” although it does not necessarily mean that bisphosphonates are safe during pregnancy, first author Aurélien Sokal said in an interview at the European Congress of Rheumatology. He is a medical student at Beaujon Hospital, Clichy, France, but conducted the study with colleagues during his time in training in the rheumatology department at Paris-Sud University.

“Very little is known about the effect of bisphosphonates on pregnancy outcomes and fetal development,” Mr. Sokal said, and they are feared for possible teratogenic effects in pregnancy because of their long half-life in bone – where they can be released even 1 year after their administration – as well as their ability to cross the placenta and high affinity for high-turnover bones, such as those in a growing fetus. He also noted that abnormalities in bone length, low birth weights, and bone diseases have been observed in rats exposed to bisphosphonates during gestation.

The study compared 23 patients with inflammatory diseases and bisphosphonate exposure during pregnancy against 92 controls with inflammatory diseases but no exposure, and 16 with bone diseases and exposure to bisphosphonates against 64 healthy controls with no underlying disease or bisphosphonate use. The patients came from a database assembled by the French Reference Center of Teratogenic Agents (CRAT) in Paris that has collected information since 1975 on patients referred for any drug exposure during pregnancy and followed their care through the end of pregnancy. The 39 patients who were exposed to bisphosphonates took the drugs during 1987-2014 within the 6 weeks preceding (n = 6) or during pregnancy (n = 33). They had a mean age of 33 years.

Systemic inflammatory diseases

The systemic inflammatory diseases found in women in the study included systemic lupus erythematosus (SLE), rheumatoid arthritis, antiphospholipid syndrome, systemic vasculitis, and other diseases. Of the 23 cases with systemic inflammatory diseases, 16 took risedronate, 5 took alendronate, 1 took etidronate, and the bisphosphonate was unknown in 1. Bisphosphonate exposure occurred before pregnancy in 2, during the first trimester in 21, second trimester in 4, third trimester in 4, and in all trimesters in 1.

Other types of medications were used significantly more often by patients with systemic inflammatory diseases than by controls: steroids (78% vs. 47%), methotrexate (26% vs. 5%), colchicine (17% vs. 2%), proton pump inhibitors (22% vs. 5%), and reproductive hormones (17% vs. 2%). Controls took antimalarials significantly more often (50% vs. 22%).

Voluntary abortions occurred at a similar rate in both exposed and unexposed women (12% vs. 9%), whereas significantly more therapeutic pregnancy terminations occurred among women exposed to bisphosphonates (17% vs. 1%). Live births occurred in 94% of the remaining exposed pregnant women, compared with 80% of controls.

Newborns were delivered at a mean of 38 weeks in both cases and controls, and there were no differences in birth weight, length, or rate of congenital malformation (9% vs. 2%).

The two malformations in neonates from exposed women had an uncertain link to bisphosphonates. One involved a neonate with severe malformative syndrome and advanced bone maturation who had a mother with SLE and was exposed to multiple drugs, including mycophenolate mofetil. The other neonate had ductus arteriosus, inguinal hernia, and negative otoacoustic emission; the baby’s mother had Crohn’s disease but had not taken known teratogenic drugs.

Two neonatal malformations among control women involved one neonate with severe malformative syndrome who had a mother with SLE but who was without exposure to known teratogenic drugs, and another with convulsant encephalopathy whose mother had systemic sclerosis and took pentoxifylline, cisapride, dihydroergocryptine, and colchicine.

However, cases had a 25% rate of neonatal complications, compared with a significantly lower 5% in controls. No infants had hypocalcemia.

Bone diseases

The 16 women with bone diseases included 9 with osteoporosis, 3 with malignancy, and 4 with miscellaneous bone conditions. A total of 5 received intravenous bisphosphonates and 11 received oral drugs (9 alendronate, 2 other). Most received a bisphosphonate in the first trimester (9 patients), but also 4 received it before pregnancy and 3 in the second trimester. More pregnancy terminations (voluntary or therapeutic) occurred among women with bone disease when compared with controls (19% vs. 3%), but the difference was not statistically significant. However in the remaining patients, live births occurred significantly less often in cases than in controls (69% vs. 100%). Birth weight, length, gestational age at birth, and the rates of congenital malformation and neonatal complications were otherwise similar.

The results of the study fall in line with those from the two major previous controlled studies on 24 women (Reprod Toxicol. 2006 Nov;22:578-9) and 21 women (Bone. 2009 Mar;44:428-30). Another series of 10 bisphosphonate-exposed pregnancies described 2 malformations, including 1 ventricular septal defect and 1 kidney and cardiac malformation (Autoimmun Rev. 2010 Jun;9:547-52). Another single case report described a neonate with bilateral talipes equinovarus (J Bone Miner Res. 2004 Oct;19:1742-5). A literature review of 78 cases of bisphosphonate exposure during or prior to pregnancy reported three malformations (Hormones [Athens]. 2011 Oct-Dec;10:280-91).

The study is ongoing and continues to collect data on the follow-up of children, Mr. Sokal said.

The study had no specific funding, and none of the investigators had disclosures to report.

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