Osteoporosis Drugs Lower Fracture Risk, but Best One Unclear

Lara C. Pullen, PhD

September 12, 2014

Several medications are able to reduce fracture risk in individuals with bone density in the osteoporotic range and/or preexisting hip or vertebral fracture, according to a systematic review published online September 9 in the Annals of Internal Medicine. However, a paucity of comparative studies makes it difficult to determine the relative effectiveness of the medications.

Effective drugs include bisphosphonates, denosumab, teriparatide, and raloxifene, report Carolyn J. Crandall, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues.

Given the lack of head-to head trials, differences in adverse effect profiles may be key for physicians and patients when choosing which drug to use, the authors note.

The authors screened 52,000 titles and found very few head-to-head comparisons between different medications used to treat osteoporosis. The ongoing Vertebral Fracture Treatment Comparisons in Osteoporotic Women (VERO) study will be completed in 2016, however, and the resulting data should shed some light on the relative efficacy and safety of the different options.

On the basis of that trial and on the observational study data that are available, Dr. Crandall and colleagues estimate that bisphosphonates, denosumab, and teriparatide treatment result in a risk reduction for vertebral fractures of 0.40 to 0.60 relative to placebo. The relative risk reduction for nonvertebral fractures was 0.60 to 0.80. Raloxifene has only been demonstrated to reduce vertebral fractures.

In other words, they estimate 60 to 89 patients need to be treated with a bisphosphonate, denosumab, teriparatide, or raloxifene to prevent 1 vertebral fracture over the course of 1 to 3 years of treatment. Fifty to 60 patients need to be treated with a bisphosphonate, denosumab, or teriparatide to prevent a single nonvertebral fracture.

Adverse Event Profiles Differ

Dr. Crandall and colleagues note that atypical subtrochanteric femur fracture is a newly recognized adverse event of bisphosphonate use. The adverse event has not been detected in clinical trials, which are not powered to detect rare events, but 2 studies that used either meta-analyses or large safety databases put the hazard ratio for the serious adverse event at 1.70 and 4.51, respectively.

The more common adverse events, such as gastrointestinal effects, hot flashes, chills, and cardiovascular events, differ between agents, but no agent is without adverse effects.

Few Data for Older Patients

In an accompanying editorial, Heike A. Bischoff-Ferrari, MD, DrPH, from the University of Zurich and Otto Meyer, MD, from the City Hospital Waid in Zurich, Switzerland, point out that a major limitation in the systematic review is that it does not reflect data for women who are older than 80 years.

Approximately 75% of osteoporotic fractures occur in patients who are 65 years of age or older, and many of these patients are older than 80 years.

There is a major limitation in the systematic review, however: It does not reflect data for women who are older than 80 years. Approximately 75% of osteoporotic fractures occur in patients who are 65 years old or older, and many of these patients are older than 80 years.

The aging of the Western population has resulted in patients older than 80 years increasingly being included in clinical trials of pharmacologic treatments for the prevention of fractures. For example, the Hip Intervention Program trial of risedronate included women aged 70 to 79 years as well as a second group of women aged 80 years or older. Although risedronate was effective in the first group, it did not reduce hip fracture risk in women aged 80 years or older.

The Hip Intervention Program trial represents just 1 study of this vulnerable population. The results from other studies of older patients are not yet in. "Because these patients sustain most fragility fractures, their insufficient representation in current clinical trials of pharmacologic treatments against fractures warrants emphasis," write Dr. Bischoff-Ferrari and Dr. Meyer.

This absence of data led Dr. Bischoff-Ferrari and Dr. Meyer to write that, "Although this is helpful information to guide clinicians and their patients, we believe that they should recognize that these conclusions may not apply to patients aged 75 years or older, and especially not to those aged 80 years or older with nonskeletal risk factors for falls. Such patients are insufficiently represented in the clinical trials of pharmacologic treatments for fracture prevention included in this careful evidence review."

This study was supported by the Agency for Healthcare Research and Quality. All authors received grant support from the agency during the conduct of the study. One coauthor reports receiving grant support from Express Scripts outside the submitted work. Another coauthor reports receiving grant support from the Agency for Healthcare Research and Quality outside the submitted work. Another coauthor reports receiving personal fees from the Emergency Care Research Institute and Veterans Affairs and a grant or pending grant support from the Agency for Healthcare Research and Quality and Veterans Affairs outside the submitted work. Dr. Bischoff-Ferrari has consulted for MSD, Amgen, Roche, and Lilly. Dr. Meyer has disclosed no relevant financial relationships.

Ann Intern Med. Published online September 9, 2014. Article full text, Editorial extract

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