ֱ

Bisphosphonate Therapy and Fracture Prevention: How Long Does It Take?

— Meta-analysis determined minimum treatment time needed to see gains

MedpageToday
A computer rendering of bone affected by osteoporosis.

About a year was determined to be the minimal timing of bisphosphonate therapy for postmenopausal women with osteoporosis to reap a benefit, according to a meta-analysis.

Looking at 10 randomized clinical trials including 23,384 women, 12.4 months (95% CI 6.3-18.4 months) on bisphosphonate therapy was the time needed to avoid one nonvertebral fracture per 100 postmenopausal women at an absolute risk reduction (ARR) of 0.010, reported William James Deardorff, MD, of the University of California San Francisco, and colleagues.

"These results suggest that bisphosphonate therapy is most likely to benefit postmenopausal women with osteoporosis who have a life expectancy greater than 12.4 months," they stated in .

Protection against fracture only appeared to get greater over treatment duration. While there was 1.0 nonvertebral fractures prevented per 100 postmenopausal women with osteoporosis receiving bisphosphonate therapy at 12 months, this increased to 1.5 fractures by 18 months of treatment.

The pooled meta-analysis also determined 200 postmenopausal women with osteoporosis would need 20.3 months (95% CI 11.0-29.7 months) of bisphosphonate therapy in order to prevent one hip fracture at an ARR of 0.005.

On top of that, 200 postmenopausal women with osteoporosis would need 12.1 months (95% CI 6.4-17.8 months) of bisphosphonate therapy to avoid one clinical vertebral fracture at an ARR of 0.005.

"The time to benefit estimates in this study apply most directly to patients who were representative of the postmenopausal women included in the randomized clinical trials," Deardorff explained to ֱ. "These results can serve as a starting point for conversations with patients about weighing the short-term harms and burdens associated with bisphosphonate therapy against the longer-term benefits in fracture risk reduction."

"While our results suggest that bisphosphonate therapy is likely to be beneficial for most older postmenopausal women with osteoporosis, it is important to consider individual values and preferences," he added.

Deardorff noted that osteoporosis often goes underdiagnosed and undertreated, despite the potentially devastating risks of fractures. While first-line treatment like bisphosphonates have demonstrated efficacy at preventing such fractures, this class of agents do carry short-term pitfalls, like gastrointestinal (GI) irritation, or severe musculoskeletal pain.

"For some older women, the delayed benefits of bisphosphonates (decreased fracture risk) may be more important than the immediate risks (most commonly upper GI symptoms)," the authors stated. "For other older women, the prospect of experiencing immediate adverse effects in exchange for a 1 in 100 chance of benefit in 12.4 months may lead to a decision to forego bisphosphonate therapy."

The 10 trials were identified through systematic reviews by the U.S. Preventive Services Task Force, the Agency for Healthcare Research and Quality, the Cochrane Library, and the Endocrine Society. All women included in the studies were postmenopausal with a diagnosis of osteoporosis based on either an existing vertebral fracture or a bone mineral density T score of -2.5 or lower. The researchers noted they chose this definition of osteoporosis "because it reflected a high-risk population that was frequently enrolled in clinical trials."

Only studies looking at the bisphosphonates alendronate (Binosto, Fosamax), risedronate (Actonel, Atelvia), and zoledronic acid (Reclast) used at first-line therapies for the prevention of nonvertebral fractures were included, as is recommended in clinical practice guidelines from the , , and the .

In the studies, participant populations ranged from 994 to 7,765, while the mean age ranged from 63-74. Follow-up time ranged from 12-48 months.

A study limitation was that some clinical trials used different dosing regimens than are commonly prescribed.

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was supported by the National Institute on Aging, the NIH, Veterans Affairs Health Services Research and Development, and resources from the San Francisco VA Health Care System.

Deardorff and co-authors disclosed no relationships with industry.

Primary Source

JAMA Internal Medicine

Deardorff WJ, et al "Time to benefit of bisphosphonate therapy for the prevention of fractures among postmenopausal women with osteoporosis" JAMA Intern Med 2021; DOI: 10.1001/jamainternmed.2021.6745.