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Osteoporosis Treatment for Postmenopausal Women at High Risk for Fracture


The Endocrine Society released guidance (2019) on the pharmacological management of osteoporosis and, based on evidence, recommends

…treating postmenopausal women at high risk of fractures, especially those who have experienced a recent fracture, with pharmacological therapies, as the benefits outweigh the risks

Definition of High Risk

  • Definition of high risk
    • Prior spine or hip fracture or
    • BMD T-score of ≤−2.5 either the hip or spine or
    • 10-year hip fracture risk ≥3% or
    • Risk of major osteoporotic fracture ≥20%

Treatment Options

  • Initial treatment for women at high risk of fractures: Bisphosphonates
    • Alendronate | Risedronate | Zoledronic acid | Ibandronate
    • Reassess fracture risk at 3 to 5 years
    • High risk should continue therapy while low-to-moderate risk may be candidates for ‘bisphosphonate holiday’
    • Ibandronate not recommended for nonvertebral or hip fracture risk reduction

Note: Osteonecrosis of the jaw (ONJ) and bisphosphonates: Absolute risk ranges from 1 in 10,000 to 1 in 100,000 | Higher risk in oncology setting | Risk may be as high as 21 in 10,000 if on medication >4 years | Increased risk with tooth extraction (0.5%)

  • Alternative initial treatment: Denosumab
    • 60 mg subcutaneously every 6 months
    • Reassess risk at 5 to 10 years as to whether patient should remain on denosumab
  • Consider SERMs (raloxifene or bazedoxifene)
    • Low risk of DVT and bisphosphonates/ denosumab not appropriate or
    • High risk of breast cancer
  • Consider menopausal hormone therapy (estrogen only for women with hysterectomy) if
    • Cannot tolerate bisphosphonates/ denosumab or bisphosphonates/ denosumab not appropriate
    • <60 years of age or <10 years beyond menopause
    • Low risk of deep vein thrombosis | No contraindications | No previous history of MI or stroke | No breast cancer
    • Symptomatic vasomotor symptoms and/or other menopausal symptoms
    • Note ACP Guidelines disagree on the use of HRT in osteoporosis

Note: Tibolone may used based on the above clinical scenarios as well | Tibolone not currently available in the US or Canada)

  • In women >60 who cannot tolerate bisphosphonates/ denosumab or bisphosphonates/ denosumab not appropriate, consider the following (in order)
    • SERM
    • HT or tibolone
    • Calcitonin
    • Calcium and vitamin D

Very High Risk of Fracture

Severe osteoporosis (i.e., low BMD T-score <−2.5 and fractures) or multiple vertebral fractures

  • Teriparatide and abaloparatide
    • These medications are parathyroid hormone and parathyroid hormone–related protein analogs
    • Anabolic agents that increase bone formation
    • Recommended for up to 2 years
    • Follow up using antiresorptive osteoporosis therapies to maintain gains
  • Romosozumab
    • Monoclonal antibody that blocks sclerostin and increases new bone formation
    • Recommended for up to 1 year
    • Recommended dosage is 210 mg monthly by subcutaneous injection
    • Following course of romosozumab, treat with antiresorptive osteoporosis therapies to maintain bone mineral density gains and reduce fracture risk

Note: Women at high risk of cardiovascular disease (e.g., MI or stroke) should not be considered for romosozumab


  • Calcitonin (nasal spray) may be an option only if patients cannot tolerate or should not be prescribed the following
    • Raloxifene | Bisphosphonates | Estrogen | Denosumab | Tibolone | Abaloparatide | Teriparatide
  • Calcium and vitamin D
    • Suggested adjunct to above therapies
    • Recommended supplementation even if women cannot tolerate other pharmacologic therapy
  • Monitoring
    • Bone mineral density
      • Dual-energy X-ray absorptiometry at the spine and hip
      • Perform every 1 to 3 years
      • Note ACP guidelines recommend against DEXA scans during 5 years of pharmacological treatment
    • Bone turnover (alternative to determine poor response or treatment nonadherence)
      • Serum C-terminal crosslinking telopeptide for antiresorptive therapy or
      • Procollagen type 1 N-terminal propeptide for bone anabolic therapy
  • Good bone health maintenance efforts are recommended for all postmenopausal women and include
    • Adequate calcium and vitamin D intake
    • Resistance and balance exercises
    • Smoking cessation
    • Limited alcohol use
    • Decreased use of drugs
    • Optimization of comorbid conditions that can harm bone
  • When choosing the best therapy
    • Multiple factors (e.g., costs, patient preferences, local guidance and drug availability etc.) will guide care
    • Individualize approach based on personalized risk/benefit

Learn More – Primary Sources:

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update

FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture