Bisphosphonate Therapy Evaluated in Postmenopausal Women with Osteoporosis

William James Deardorff, MD

A recent meta-analysis from San Francisco found that the time to benefit (TTB) of bisphosphonate therapy for the prevention of 1 nonvertebral and similar fractures in postmenopausal women with osteoporosis was 12.4 months per 100 participants.

The results suggested that bisphosphonate therapy was most likely to benefit postmenopausal women with osteoporosis with a life expectancy greater than that amount of time.

According to investigators led by William James Deardorff, MD, Department of Medicine at the University of California, the choice to initiate the therapy has required balancing shorter-term harms and burdens such as musculoskeletal pain and gastroesophageal irritation.

To aid clinicians in decision making regarding the initiation of this therapy, Deardoff and colleagues conducted a meta-analysis of randomized clinical trials involving bisphosphonates to assess the TTB for the prevention of fractures among the aforementioned patient population.

The Methods

The investigators identified randomized clinical trials involving bisphosphonate therapy from 5 published reviews including a 2018 systematic review commissioned by the US Preventive Services Task Force, a 2021 comparative effectiveness review prepared for the Agency for Healthcare Research and Quality, 2 systematic reviews from the Cochrane Library published in 2008, and a 2019 systematic review and network meta-analysis partially funded by the Endocrine Society.

Forward citation tracing through Google Scholar was performed from December 2020 to April 2021, to identify additional studies, followed by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for meta-analyses.

In the end, a total of 67 full-text articles were identified, with 10 randomized clinical trials comprised of a total of 23, 384 postmenopausal women with osteoporosis.

Among those studies, the total number of participants ranged from 994 to 7765 women with a mean age of 63 years to 74 years.

Investigators established the primary outcome as the time to 3 specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.010) for the first nonvertebral fracture.

For secondary outcomes, they assessed the tome to 4 specific ARR thresholds (0.001, 0.002, 0.005, and 0.010) for the first hip fracture, first clinical vertebral fracture, and first clinical fracture of any type.

The Findings

Investigators reported that in the pooled meta-analysis found that 12.4 months (95% CI, 6.3-18.4 months) were needed to avoid 1 nonvertebral fracture per 100 postmenopausal women receiving bisphosphonate therapy at an ARR of 0.010.

Additionally, to prevent 1 hip fracture, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 20.3 months (95% CI, 11.0-29.7 months) at an ARR of 0.005. Further, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 12.1 months (95% CI, 6.4-17.8 months) to avoid 1 clinical vertebral fracture at an ARR of 0.005.

The test of heterogeneity across studies was deemed not statistically significant. However, the time to an ARR of 0.010 varied from 6.7 months (95% CI, 2.1-15.7 months) in the pooled analysis of 4 clinical trials involving risedronate to 22.7 months (95% CI, 3.0-91.4 months) and in another study involving alendronate.

“These results can be used to inform discussions between clinicians and older postmenopausal women who seek to balance the potential immediate harms and burdens of bisphosphonate therapy with the delayed benefit of decreased fracture risk,” the team wrote.

The study, “Time to Benefit of Bisphosphonate Therapy for the Prevention of Fractures Among Postmenopausal Women With Osteoporosis A Meta-analysis of Randomized Clinical Trials ,” was published online in JAMA Internal Medicine.