What is the role of bisphosphonates in the treatment of menopausal women?

Updated: Jun 06, 2018
  • Author: PonJola Coney, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Bisphosphonates (alendronate, etidronate, ibandronate, risedronate, and zoledronic acid), are the most useful pharmacologic intervention. Most of them prevent vertebral fractures, as do raloxifene, calcitonin, and estrogen. Some bisphosphonates (alendronate, risedronate, and zoledronic acid) and estrogen prevent hip and other nonvertebral fractures. Whether bisphosphonates prevent fractures more effectively than the other therapies is unknown. [5] Bisphosphonates increase BMD more than raloxifene and calcitonin do. [29, 30, 31]

Alendronate, risedronate, and ibandronate are all both widely used and effective. In the Vertebral Efficacy With Risedronate Therapy (VERT) study, which included 2458 postmenopausal women with vertebral fractures from 110 centers, administration of risedronate at a dose of 5 mg for 36 months yielded a statistically significant reduction in the relative risk of new vertebral fractures. [31] The cumulative incidence of nonvertebral fractures was also reduced.

In May 2010, the Journal of the American Medical Association reported a possible association between bisphosphonates and atypical femoral fractures. [32] Further data on this possibility should be forthcoming, but a letter to the editor in the New England Journal of Medicine presented data disputing the extent of these atypical fractures and emphasized that overall, fracture rates are much lower in patients who take bisphosphonates than in those who do not. [33]

A population-based nationwide analysis of atypical fractures in bisphosphonate users in Sweden concluded that for individual patients with a high risk of osteoporotic fractures, the absolute risk of osteoporotic fractures is small in comparison with the beneficial effects of the medication. [34]

Initially, both alendronate and risedronate were introduced with daily dosing for treatment of osteoporosis. Currently, patients can be prescribed a weekly dose of either alendronate or risedronate, which increases the tolerability of these agents and reduces side effects. Ibandronate is approved for monthly use, and zoledronic acid is approved for once-yearly use.

The main adverse effects of bisphosphonates continue to be gastrointestinal upset and reflux. Patients with significant gastroesophageal reflux disease (GERD) should be discouraged from bisphosphonate use unless it is approved by a gastroenterologist. Supplementation with calcium 1000-1500 mg/day remains a mainstay of prevention, as does vitamin D supplementation and regular weight-bearing exercise. Excessive salt, animal protein, alcohol, and caffeine offset these benefits.

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