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 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

KEY POINTS:

• 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