Drugs for Osteoporosis

Osteoporosis Overview - Brittle Bones Battle

• Definition: Low bone mass & microarchitectural deterioration, leading to ↑ bone fragility. WHO diagnostic criterion: T-score ≤ -2.5.
• Major Risk Factors:
  • Advanced age
  • Postmenopausal status (↓ estrogen)
  • Long-term corticosteroid use
  • Smoking, excessive alcohol
• Goals of Therapy:
  • Prevent fractures
  • ↑ Bone Mineral Density (BMD)
  • Reduce pain, maintain function

⭐ Most common osteoporotic fractures: vertebral, hip, and wrist.

Bisphosphonates - Mighty Mineral Binders

• MOA: Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity and bone resorption.
  • 📌 BPP: Bisphosphonates Prevent Pores.
• Key Agents:
  • Oral: Alendronate, Risedronate, Ibandronate
  • IV: Zoledronic acid, Pamidronate
• Oral Administration:
  • Empty stomach (poor absorption).
  • Full glass of plain water.
  • Remain upright for 30-60 min (Alendronate/Risedronate 30 min; Ibandronate 60 min) to prevent esophagitis.
• Major ADRs:
  • Esophagitis ⚠️ (oral)
  • Osteonecrosis of the Jaw (ONJ)
  • Atypical femoral fractures (long-term use)
  • Hypocalcemia; Flu-like symptoms (IV)
• ⭐

  Zoledronic acid is given once yearly IV for osteoporosis treatment.

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SERMs & Denosumab - Targeted Bone Defenders

Anabolic Agents & Calcitonin - Bone Growth Boosters

• Anabolic Agents: Stimulate new bone formation.

  • Teriparatide, Abaloparatide: Recombinant PTH analogues.
    • MOA: Intermittent exposure stimulates osteoblasts > osteoclasts, ↑ bone mass.
    • Use: Severe osteoporosis, patients at high fracture risk. Max 2 years therapy.
    • ADRs: Hypercalcemia, orthostatic hypotension, leg cramps.
    • ⚠️ BBW: Osteosarcoma risk (rats); avoid in Paget's disease, prior skeletal radiation.

  ⭐ Teriparatide treatment should be followed by an anti-resorptive agent to maintain BMD gains.

• Calcitonin (Salmon):

  • MOA: Directly inhibits osteoclasts, ↓ bone resorption; provides analgesic effect.
  • Forms: Nasal spray, injection.
  • Use: Limited efficacy for osteoporosis; mainly for pain relief from acute vertebral compression fractures.

High‑Yield Points - ⚡ Biggest Takeaways

• Bisphosphonates (e.g., Alendronate) are first-line agents, inhibiting osteoclast activity; key risks include ONJ and atypical femoral fractures. Specific administration is crucial.
• Denosumab, an anti-RANKL monoclonal antibody, potently inhibits osteoclast function; administered as an SC injection every 6 months.
• Teriparatide (recombinant PTH) is an anabolic agent that stimulates osteoblast activity and bone formation; reserved for severe osteoporosis.
• Raloxifene, a SERM, inhibits bone resorption; it increases the risk of DVT/PE but decreases the risk of invasive breast cancer.
• Romosozumab, an anti-sclerostin antibody, has a dual effect: it increases bone formation and decreases bone resorption.
• Adequate Calcium and Vitamin D supplementation is essential alongside all pharmacological therapies for osteoporosis.