Osteoporosis: Pathophysiology, Risk Factors, Diagnosis, and Management

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to enhanced bone fragility and fracture risk.

Pathophysiology

Bone remodeling imbalance: osteoclast‑mediated resorption outpaces osteoblast‑mediated formation. Peak bone mass achieved ~age 30; thereafter, net loss ~0.5–1%/yr, accelerating at menopause (estrogen withdrawal → ↑ RANKL/OPG ratio → osteoclast activation).

Major Risk Factors

Non‑Modifiable	Modifiable
Age >50	Low calcium/vitamin D intake
Female sex	Sedentary lifestyle
Menopause (early/surgical)	Smoking
Family history (hip fracture)	Excessive alcohol (>2 units/day)
White/Asian ethnicity	Low BMI (<19 kg/m²)
Prior fragility fracture	Glucocorticoids (≥5 mg prednisone ≥3 mo)
Rheumatoid arthritis, T1DM, celiac	Proton‑pump inhibitors (long‑term)
Certain meds (aromatase inhibitors, GnRH agonists)	Falls risk (poor vision, balance, meds)

Diagnosis

• DXA (T‑score): ≤ –2.5 = osteoporosis; –1.0 to –2.5 = osteopenia.
• FRAX® – 10‑year major osteoporotic / hip fracture probability (with/without BMD).
• Vertebral fracture assessment (VFA) or lateral spine X‑ray.

Management

1. Lifestyle: Weight‑bearing + resistance exercise 3×/wk; balance training; fall‑proof home.
2. Nutrition: Calcium 1000–1200 mg/day (diet + supplement); Vitamin D 800–2000 IU/day (target 25‑OH‑D >30 ng/mL).
3. Pharmacotherapy (if T ≤ –2.5 or FRAX high risk):
   • First‑line: Oral bisphosphonates (alendronate, risedronate) or IV zoledronic acid.
   • Alternatives: Denosumab (SC q6mo), Anabolic agents (teriparatide, romosozumab) for very high risk.
4. Monitoring: DXA q1–2 yr; adherence counseling.

Fracture prevention is the goal. Hip fracture carries 20–30% 1‑year mortality; vertebral fractures increase subsequent fracture risk 5‑fold.