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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