Osteoporosis: new review details benefits, harms of long-term drug therapy

  • Fink HA & al.
  • Ann Intern Med
  • 23 Apr 2019

  • International Clinical Digest
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Takeaway

  • Long-term alendronate and zoledronic acid reduce fracture risk in women with osteoporosis.
  • Benefits of bisphosphonates outweigh harms of rare adverse events such as atypical femoral fractures and osteonecrosis of the jaw, according to a prominent review of the literature.

Why this matters

  • An accompanying position paper and editorial recommend new research on who should be considered for drug holidays to reduce harms, when holidays should begin, and how long they should last.

Study design

  • Systematic review of 9 unique clinical trials and 11 unique observational studies after a search of Medline, EMBASE, and Cochrane library.
  • Funding: Agency for Healthcare Research and Quality; NIH.

Key results

  • In osteoporotic women, 4 years of alendronate (vs placebo) lowers clinical fractures (HR, 0.64; 95% CI, 0.50-0.82) and radiographic vertebral fractures.
  • Alendronate has no benefit for women with osteopenia.
  • In both osteopenic and osteoporotic women, zoledronic acid (vs placebo) taken long-term lowers clinical fractures (HR, 0.73; 95% CI, 0.60-0.90), including nonvertebral and clinical vertebral fractures.
  • For every 1000 women treated with bisphosphonates for 4-6 years, 50-70 will avoid a clinical fracture, whereas 2 will be harmed by subtrochanteric or femoral shaft fracture.
  • Raloxifene taken long-term reduces vertebral fractures, but fails to reduce hip fractures and raises risk for venous thromboembolism.
  • Denosumab should not be subject to drug holidays.