Osteoporosis Treatment for Postmenopausal Women at High Risk for Fracture

SUMMARY:

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: 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 (ie, 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
    • Women at high risk of cardiovascular disease and stroke: Should not be considered for romosozumab

KEY POINTS:

  • Calcitonin (nasal spray) may be an option only if patients can not 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 if women can not tolerate medications
  • Monitoring
    • Bone mineral density
      • Dual-energy X-ray absorptiometry at the spine and hip
      • Perform every 1 to 3 years
    • 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