Bisphosphonate therapy may prevent fracture in postmenopausal women with osteoporosis

Despite potential side effects, bisphosphonate therapy may benefit postmenopausal women with osteoporosis by preventing fractures, according to a study published in JAMA Internal Medicine.

“Osteoporosis is often underdiagnosed and undertreated despite the potentially devastating consequences of certain fractures,” author William James Deardorff, MD, of the division of geriatrics in the department of medicine at University of California, San Francisco, told Healio.

Bisphosphonates have been shown to reduce fracture risk as a first-line treatment for osteoporosis, Deardorff said, but clinicians must weigh the longer-term benefit in preventing fractures against potential short-term harms and burdens such as gastrointestinal irritation, which often is reported as the reason for discontinuing treatment.

“We sought to assess the time to benefit of bisphosphonates in preventing different fracture types in postmenopausal women with osteoporosis to help guide clinical discussions between patients and clinicians,” Deardorff said.

The researchers identified 10 randomized clinical trials from five published reviews involving 23,384 postmenopausal women diagnosed with osteoporosis based on an existing vertebral fracture or a bone mineral density T-score of –2.5 or lower.

The mean age of the participants ranged from 63 years (standard deviation, 7 years) to 74 years (standard deviation, 3 years), and most were white (typically > 90%) when race and/or ethnicity were reported.

These trials only involved alendronate, risedronate and zoledronic acid because they are recommended by clinical guidelines as first-line therapies for reducing nonvertebral fractures in postmenopausal women with osteoporosis.

Dosages included 5 mg to 20 mg per day for alendronate, 2.5 mg to 5 mg per day for risedronate and 5 mg per year for zoledronic acid.

The primary outcome was the time to three specific absolute risk reduction (ARR) thresholds (0.002, 0.005 and 0.01) for the first nonvertebral fracture. The secondary outcomes included the time to four specific ARR thresholds (0.001, 0.002, 0.005 and 0.01) for the first hip fracture, first clinical vertebral fracture and first clinical fracture of any type.

Follow-up durations ranged from 12 to 48 months. According to the meta-analysis, benefits increased in a nearly linear manner as follow-up durations increased. For example, the researchers said, the number of nonvertebral fractures prevented per 100 postmenopausal women with osteoporosis on bisphosphonate therapy increased from one (95% CI, 0.4-1.6) at 12 months to 1.5 (95% CI, 0.8-2.3) at 18 months.

According to the researchers, 100 postmenopausal women with osteoporosis on bisphosphonate treatment would need to be treated for 12.4 months (95% CI, 6.3-18.4 months) to prevent one nonvertebral fracture (ARR = 0.01), which Deardorff called the study’s “most notable finding.”

Also, 200 of these patients would need 6.5 months of treatment (95% CI, 2.2-10.9 months) to prevent one nonvertebral fracture (ARR = 0.005), and 500 would need 3.3 months of treatment (95% CI, 0.2-6.5 months) to prevent one nonvertebral fracture (ARR = 0.002).

Similarly, 200 of these patients would need 20.3 months of treatment (95% CI, 11-29.7 months) to prevent one hip fracture (ARR = 0.005) or 7.7 months of treatment (95% CI, 3.3-12.1 months) to prevent any clinical fracture (ARR = 0.005). Furthermore, 200 of these patients would need 12.1 months of treatment (95% CI, 6.4-17.8 months) to prevent one clinical vertebral fracture (ARR = 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,” said Deardorff.

Doctors can use these results to begin conversations with patients about weighing the short-term harms and burdens associated with bisphosphonate therapy against the longer-term benefits in fracture risk reduction.

The delayed but decreased risk for fractures with bisphosphonates may outweigh the potential for upper GI symptoms for some older women, the researchers said. Others may prefer not to take a one in 100 chance for reducing fracture risks more than a year away if immediate adverse effects are possible, the researchers continued.

“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,” Deardorff said.

The researchers are looking ahead to additional studies as well.

“Older adults with frailty and multiple comorbidities were commonly excluded from most randomized clinical trials involving osteoporosis medications despite this population being at high risk for fractures,” Deardorff said. “Further research is needed in this population to help guide treatment decisions.”

For more information:

William James Deardorff, MD, can be reached at william.deardorff@ucsf.edu.