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An updated, new guideline from the American College of Physicians caught my eye because of two main reasons. First, it is written in a very simple, clear and didactic way, so that all health-care providers can easily understand and implement it [1]. Second, the recommendation on postmenopausal hormone therapy (HT) was somewhat unexpected. One should pay attention to the phrasing of the title of the publication, which points at a specific target aim – prevention of fractures in patients with established low bone mass or osteoporosis. The article includes 387 citations, and thus it seems that a very thorough analysis was made.

Here are the main messages in regard to women:

  • High-quality evidence showed that bisphosphonates, including alendronate, risedronate, and zoledronic acid, reduce vertebral, non-vertebral, and hip fractures compared with placebo in postmenopausal osteoporotic women.
  • High-quality evidence showed that treatment with teriparatide reduces radiographic vertebral and non-vertebral fractures compared with placebo in postmenopausal osteoporotic women.
  • High-quality evidence showed that treatment with denosumab reduces radiographic vertebral, non-vertebral, and hip fractures compared with placebo in postmenopausal osteoporotic women.
  • High-quality evidence showed that raloxifene reduces vertebral fractures in osteoporotic women; however, it did not statistically significantly decrease the risk for non-vertebral or hip fractures compared with placebo. Bazedoxifene is FDA-approved in combination with conjugated estrogens for the prevention of osteoporosis (20 mg, with 0.45 mg conjugated estrogen). The systematic review did not find any randomized controlled trials with this combination that had primary fracture outcomes.
  • Moderate-quality evidence showed that the overall effect of calcium or vitamin D alone on fracture risk is uncertain.
  • Evidence is insufficient to determine the comparative effectiveness of pharmacologic therapy or the superiority of one medication over another, within the same class or among classes, for prevention of fractures. Network meta-analyses addressing the lack of head-to-head comparisons between the drugs mostly show no statistically significant differences among the various therapies.
  • Evidence is insufficient to conclusively show the effect of physical activity on fracture risk.

As for HT, the guideline says: Moderate-quality evidence showed no difference in reduced fracture with estrogen treatment in postmenopausal women with established osteoporosis. This differs from the 2008 guideline, which reported high-quality evidence that estrogen therapy was associated with reduced risk for vertebral, non-vertebral, and hip fractures in postmenopausal women. Studies included in the 2008 guideline focused on postmenopausal women or those with low bone density as opposed to the newer data, which focused on postmenopausal women with established osteoporosis. Thus, the current claim actually favors the use of HT for primary prevention of fractures in postmenopausal women in general, but not as a strategy for secondary prevention or treatment of fractures in women with already established osteoporosis.

In another section of the guideline, the potential adverse effects of the various medications are outlined. The quote for HT was: high-quality evidence from the Women’s Health Initiative showed that menopausal hormone therapy was associated with increased risk for cerebrovascular accidents and venous thromboembolic events. Another study showed that estrogen plus progestin therapy was associated with more invasive breast cancer, more node-positive tumors, and more deaths due to breast cancer than. As a result, the bottom line is: The American College of Physicians recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence).



  • Amos Pines
    Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med 2017;166:818-39
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