Makindo Medical Notes

🦴 Osteoporosis is the most common metabolic bone disease, affecting ~200 million people worldwide. It is characterized by decreased bone mass and deterioration of bone microarchitecture, leading to fragility fractures. Hip fractures carry up to a 30% one-year mortality in the elderly, highlighting its clinical importance.

About

• Defined by reduced bone strength predisposing to fractures.
• Diagnosis: T-score < -2.5 on DEXA, or fragility fracture in an at-risk patient.
• Causes: Ageing, genetics, lifestyle factors, medications (e.g. steroids), and secondary medical conditions.

WHO Classification (T-Score) measured by DEXA scan

• ✅ Normal: -1.0 or higher
• ⚠️ Osteopenia: -1.0 to -2.5
• ❌ Osteoporosis: < -2.5
• 💥 Established Osteoporosis: < -2.5 + fragility fracture

Epidemiology & Prevalence in Older Women 👩‍🦳

• Postmenopausal Women: Oestrogen has a protective effect on bone by suppressing osteoclast activity. After the menopause, rapid bone loss occurs — up to 20% of bone mass can be lost in the first 5–7 years.
• Prevalence: Around 1 in 2 women over the age of 50 will experience an osteoporosis-related fracture in their lifetime, compared with about 1 in 5 men.
• Fragility Fractures: Most common at the vertebrae, hip, and distal radius. Hip fractures are particularly devastating, with a 20–30% one-year mortality in older adults.
• Global Burden: WHO recognises osteoporosis as one of the most important non-communicable diseases. In the UK, ~3 million people are affected, and >500,000 fragility fractures occur each year.
• Silent Disease: Many women remain undiagnosed until a fracture occurs, hence why screening with DEXA is recommended in high-risk groups (e.g. women ≥65, those with premature menopause, or long-term steroid use).

💡 Teaching Tip: Think of osteoporosis in older women as the “silent thief of bone” — it progresses quietly until the first fracture. Always take a thorough fracture and falls history in women over 65.

Pathophysiology

• Normal bone is constantly remodelled by osteoclasts (resorption) and osteoblasts (formation).
• In osteoporosis ➝ osteoclast activity > osteoblast activity ➝ net bone loss.
• Contributing factors: estrogen deficiency, vitamin D/calcium deficiency, chronic inflammation, steroids, endocrine disorders.

Causes of Secondary Osteoporosis

• 💊 Steroids (>7.5 mg prednisolone daily >3 months)
• 🦠 Inflammatory: Rheumatoid arthritis, SLE, ankylosing spondylitis
• 🧬 Endocrine: Hyperthyroidism, hyperparathyroidism, hypogonadism
• 🚬 Smoking, 🍷 alcohol >4 units/day, low BMI <19
• 🔬 Malabsorption: Coeliac disease, Crohn’s disease, dietary deficiency
• 🧪 Other: CKD, CLD, Type 1 diabetes, multiple myeloma

Clinical Presentation

• Often silent until fracture occurs.
• 📉 Vertebral compression fractures: back pain, loss of height, kyphosis (“dowager’s hump”).
• 👵 Fragility fractures: hip (#NOF), wrist (Colles’), proximal humerus.
• May present with abdominal distension due to collapsed vertebrae.

Investigations

• Bloods: FBC, U&E, LFTs, TFTs, calcium, vitamin D, PTH (exclude secondary causes).
• DEXA Scan: Gold standard for BMD.
• FRAX / QFracture: Risk calculators used in UK primary care to decide who to scan/treat.
• Spinal X-rays may show vertebral wedge fractures.

Management

• 🌿 Lifestyle: stop smoking, reduce alcohol, weight-bearing exercise, prevent falls, adequate calcium & vitamin D.
• 💊 Pharmacological:
  • Bisphosphonates (e.g. alendronate): first line; improve BMD & reduce fracture risk.
  • Denosumab: SC injection every 6 months, anti-RANKL antibody.
  • Raloxifene: SERM, useful in post-menopausal women at risk of breast Ca.
  • Teriparatide: recombinant PTH, for severe osteoporosis (T-score < -4 or multiple fractures).
• 👴 Men: consider testosterone if hypogonadal.

Special Case: Steroid-Induced Osteoporosis

• At risk if on >7.5 mg prednisolone daily for >3 months.
• >65 yrs ➝ bone protection offered directly.
• <65 yrs ➝ DEXA scan then treat if T-score < -1.5.

Drug Management of Osteoporosis 💊

• Bisphosphonates (Alendronate, Risedronate, Zoledronic Acid) 🦴
  • Mechanism: Inhibit osteoclast-mediated bone resorption by binding to hydroxyapatite in bone.
  • Indications: First-line for postmenopausal women, men with osteoporosis, and glucocorticoid-induced osteoporosis.
  • Dosing:
    • Alendronate: 70 mg once weekly (oral)
    • Risedronate: 35 mg once weekly (oral)
    • Zoledronic acid: 5 mg IV yearly
  • Administration: Oral forms must be taken fasting with water, patient upright ≥30 minutes, to avoid oesophageal irritation.
  • Adverse Effects: Oesophagitis, gastric irritation, hypocalcaemia, rare osteonecrosis of the jaw (ONJ), atypical femoral fractures.
  • Monitoring: Check calcium & vitamin D before starting. Dental review advised for IV forms (ONJ risk).
• Denosumab (Anti-RANKL antibody) 🧬
  • Mechanism: Monoclonal antibody against RANKL ➝ prevents osteoclast formation ➝ reduced bone resorption.
  • Dose: 60 mg SC every 6 months.
  • Indications: Postmenopausal women and men at high fracture risk, especially those intolerant of bisphosphonates or with renal impairment (works even with eGFR <30).
  • Adverse Effects: Hypocalcaemia, ONJ, skin infections, rebound vertebral fractures if abruptly stopped.
  • Monitoring: Check calcium, vitamin D, and renal function before each dose.
• Raloxifene (SERM) 👩
  • Mechanism: Selective oestrogen receptor modulator: oestrogen agonist on bone, antagonist on breast/uterus.
  • Indications: Postmenopausal osteoporosis, especially in women with ↑ breast cancer risk.
  • Adverse Effects: Hot flushes, leg cramps, ↑ risk of venous thromboembolism (VTE).
  • Limitations: Reduces vertebral fractures but not hip fractures.
• Hormone Replacement Therapy (HRT) 💃
  • Mechanism: Restores oestrogen, reducing bone resorption.
  • Indications: Postmenopausal women with vasomotor symptoms and osteoporosis risk.
  • Adverse Effects: ↑ risk of breast cancer, endometrial cancer (if no progestogen), stroke, VTE.
  • Use: Short-term in younger postmenopausal women; not first-line for osteoporosis alone.
• Teriparatide & Abaloparatide (Anabolic Agents) 💥
  • Mechanism: Recombinant parathyroid hormone analogues; intermittent dosing stimulates osteoblasts & bone formation.
  • Dose: Teriparatide 20 mcg SC daily; max duration 18 months (lifetime limit).
  • Indications: Severe osteoporosis (T-score < -4, or multiple fragility fractures) or failure of other therapies.
  • Adverse Effects: Leg cramps, hypercalcaemia, dizziness; animal studies show risk of osteosarcoma (rare in humans).
• Romosozumab (Anti-sclerostin antibody) 🔬
  • Mechanism: Increases bone formation & decreases resorption.
  • Dose: 210 mg SC monthly for 12 months (newer therapy).
  • Indications: Severe postmenopausal osteoporosis at high fracture risk.
  • Adverse Effects: Possible ↑ cardiovascular risk (MI, stroke).
• Calcitonin (rarely used) 🐟
  • Mechanism: Inhibits osteoclasts; derived from salmon calcitonin.
  • Use: Now rarely used due to limited efficacy and risk of malignancy with long-term use.

Exam Tips 🎓

💡 Bisphosphonates = first-line. 💡 Denosumab safe in renal impairment. 💡 Raloxifene → VTE risk, but ↓ breast cancer. 💡 Teriparatide → only drug that is anabolic (builds bone). 💡 Always correct vitamin D & calcium before starting antiresorptive drugs.

Exam Tip 🎓

💡 An elderly woman with a low-impact Colles’ fracture ➝ always think osteoporosis. 💡 Vertebral wedge fractures ➝ loss of height + kyphosis (“dowager’s hump”). 💡 DEXA = diagnostic, FRAX = risk prediction.

References

• NICE CG146: Osteoporosis: assessing the risk of fragility fracture
• FRAX® Fracture Risk Assessment Tool
• SIGN 142: Osteoporosis Management