Pharmacology
Osteoporosis drugs
Pharmacology

Osteoporosis drugs

Bisphosphonates, denosumab, anabolics (teriparatide, romosozumab), SERM, HRT, calcium/vit D — when to use each.

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When to treat

  • DEXA T-score ≤ -2.5 (lumbar spine, total hip, or femoral neck)
  • Hip or vertebral fracture (regardless of T-score)
  • T-score -1.0 to -2.5 (osteopenia) WITH 10-yr FRAX risk: ≥3% hip OR ≥20% major osteoporotic fracture
  • Long-term glucocorticoids (≥5 mg/day prednisone × ≥3 mo)

Bisphosphonates (first-line)

  • Oral: alendronate (weekly), risedronate (weekly), ibandronate (monthly)
  • IV: zoledronic acid (yearly) — for noncompliant or GERD
  • Mechanism: bind to bone hydroxyapatite → inhibit osteoclast
  • Take with full glass of water, sit upright × 30 min, empty stomach — prevents esophagitis
  • Side effects: esophagitis (oral), flu-like with first IV dose, atypical FEMUR fracture (long use), OSTEONECROSIS of the JAW (esp dental work), hypocalcemia
  • Drug holiday after 5 years (oral) or 3 years (IV) in low-risk patients

Denosumab (RANK-L inhibitor)

  • SC every 6 months
  • Mechanism: monoclonal antibody to RANK-L → ↓ osteoclast formation
  • Side effects: hypocalcemia (replete first), ONJ, atypical fractures, ↑ infections, REBOUND FRACTURES if discontinued (must transition to bisphosphonate)
  • Used in CKD where bisphosphonates contraindicated

Anabolic agents (build bone)

  • Teriparatide (PTH 1–34): SC daily × max 2 years — recombinant PTH; sequential before/after antiresorptive
  • Abaloparatide: similar to teriparatide; PTHrP analog
  • Romosozumab (anti-sclerostin): SC monthly × 12 mo; ↑ formation + ↓ resorption; risk: cardiovascular events (avoid in recent MI/stroke)
  • ALL anabolics: indicated for severe osteoporosis or failure of bisphosphonates
  • Always FOLLOW with bisphosphonate or denosumab to preserve gains

Other agents

  • Raloxifene (SERM): partial estrogen agonist on bone, antagonist on breast; ↓ vertebral fractures + ↓ breast CA; ↑ VTE, hot flashes
  • Estrogen / HRT — last-line; CV/breast CA risks
  • Calcium 1000–1200 mg/day + vit D 800–1000 IU — foundation for all
  • Calcitonin (rare) — for acute pain from vertebral compression fractures

Glucocorticoid-induced osteoporosis

  • Prednisone ≥5 mg/day × ≥3 mo → DEXA, calcium, vit D, consider bisphosphonate
  • Highest fracture risk in first 3–6 months of steroid use
  • Strong evidence for bisphosphonate in this population — start early

High-yield pearls

  • Bisphosphonates: full glass of water, sit upright × 30 min, empty stomach (esophagitis prevention)
  • Osteonecrosis of the jaw — get dental clearance BEFORE starting bisphosphonate or denosumab
  • Denosumab DC → rebound fractures within 1 year — MUST transition to bisphosphonate
  • Teriparatide max 2 years (animal osteosarcoma signal) — follow with antiresorptive
  • Atypical femur fracture: thigh pain with long-term bisphosphonate use → image, consider drug holiday
  • Steroid users (≥5 mg prednisone ≥3 mo): start bisphosphonate early — high fracture risk first 3–6 mo
  • Romosozumab CV risk: AVOID in recent MI or stroke
  • Raloxifene: ↓ vertebral fx AND ↓ breast cancer; ↑ VTE
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