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NIH committee uncovers gaps in osteoporosis drug therapy evidence

Overall, evidence indicates that drug therapies for osteoporosis reduce the risk for clinical fractures, but long-term use may increase the risk for rare, but serious harms, according to findings published in Annals of Internal Medicine.

However, there are significant gaps in this evidence regarding clinical decisions for initiating treatment, duration of treatment and drug holidays, according to the NIH Pathways to Prevention Workshop.

“Optimal long-term osteoporosis drug treatment is uncertain,” Howard A. Fink, MD, MPH, from the University of Minnesota and Minneapolis VA Health Care System, and colleagues wrote.

Fink and colleagues reviewed 35 trials and 13 observational studies of men or postmenopausal women aged 50 years or older to determine the risks for incident fractures and harms with long-term osteoporosis drug therapy (more than 3 years) vs. control, and continuing therapy vs. discontinuing or temporarily stopping treatment. All studies had low or medium risk of bias.

The researchers found that women with osteoporosis who took alendronate for 4 years had a decreased risk for clinical fractures (HR = 0.64; 95% CI, 0.5-0.82) and radiographic vertebral fractures. Women taking raloxifene for 4 years had a reduced risk for vertebral fractures, but not nonvertebral fractures. Raloxifene also heightened the risk for deep venous thrombosis and pulmonary embolism.

Use of zoledronic acid decreased the risk for clinical nonvertebral fractures and vertebral fractures in women with osteopenia or osteoporosis (HR = 0.73; 95% CI, 0.6-0.9).

Conversely, long-term use of bisphosphonates increased rare harms, including the risk for atypical femoral fractures and osteonecrosis of the jaw.

Hormone therapy for 5 to 7 years decreased clinical fractures, including hip fractures; however, it also elevated the risk for serious harms, including CVD, cognitive impairment and invasive breast cancer, in women with unspecified osteoporosis status.

Continuing bisphosphonate treatment after 3 to 5 years decreased radiographic vertebral fractures and clinical vertebral fractures, but not nonvertebral fractures, compared with discontinuing therapy.

There was insufficient evidence to determine the effects of long-term use of other FDA-approved osteoporosis drugs, such as risedronate, ibandronate, denosumab, teriparatide and abaloparatide.

Additionally, there was a lack of data to suggest the benefits and harms of bisphosphonate drug holidays.

The NIH convened the Pathways to Prevention Workshop to examine the evidence on the effectiveness of long-term drug therapies to prevent fractions in patients with osteoporosis, including Fink and colleagues’ review, as well as any research gaps and needs for future research.

The NIH workshop committee concluded that the general safety and effectiveness of osteoporosis drug therapies have been established but there are “important gaps to guiding clinical management decisions.”

“There are questions about who should be prioritized for treatment, when treatment should be initiated, which medication should be started first, how long treatment should be maintained, how treatment should be monitored, in what order treatments should be used, and whether drug holidays should be considered or implemented,” Albert Siu, MD, MSPH, professor and chair emeritus in geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, and a member of the NIH workshop committee, and colleagues wrote. “Answers to these questions are needed to realize the population benefits from osteoporosis drug therapy.”

The committee recommended that future research evaluate the effects of drug holidays, newer treatments and patient and clinical barriers to getting screened for osteoporosis and adhering to treatment regimens. – by Alaina Tedesco

Disclosures: Fink and Siu report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.