Key Facts

The musculoskeletal system provides structural support, facilitates movement, and protects vital organs. Skeletal muscle comprises ~40% of body weight and is under voluntary control via somatic motor neurones.

Epidemiology

Osteoporosis affects approximately 3 million people in the UK, causing >500,000 fragility fractures annually. Osteoarthritis affects ~8.75 million people. Musculoskeletal conditions are the leading cause of disability and the most common reason for GP consultation.

Aetiology

Bone health depends on:

• Peak bone mass (achieved by age 25-30)
• Rate of bone loss (accelerated post-menopause due to oestrogen withdrawal)
• Risk factors: Age, female sex, family history, low BMI, smoking, alcohol, corticosteroid use, immobility

Muscle disorders:

• Inflammatory myopathies (polymyositis, dermatomyositis)
• Inherited myopathies (Duchenne, Becker muscular dystrophy)
• Metabolic myopathies (McArdle disease, mitochondrial)

Pathophysiology

Muscle contraction (sliding filament theory):

1. ACh at NMJ → motor end-plate depolarisation → action potential along sarcolemma
2. T-tubule activation → Ca²⁺ release from SR
3. Ca²⁺ binds troponin C → tropomyosin moves → exposes myosin-binding sites on actin
4. ATP-dependent cross-bridge cycling → sarcomere shortening
5. Ca²⁺ reuptake by SERCA pump → relaxation

Bone remodelling:

• Osteoblasts (bone formation): Produce osteoid (type I collagen + hydroxyapatite); stimulated by PTH (intermittent), oestrogen, mechanical loading
• Osteoclasts (bone resorption): Multinucleated cells from monocyte lineage; activated by RANKL, inhibited by OPG (osteoprotegerin); secrete H⁺ and cathepsin K
• PTH: Continuous exposure → net resorption; intermittent exposure → net formation (basis for teriparatide therapy)

Osteoporosis

• Often asymptomatic until fracture
• Vertebral crush fractures: Height loss, kyphosis, back pain
• Fragility fractures: Hip, wrist (Colles'), proximal humerus, vertebral

Osteomalacia

• Bone pain (diffuse), proximal myopathy, waddling gait
• Looser zones (pseudofractures) on X-ray

Inflammatory Myopathy

• Proximal muscle weakness (difficulty climbing stairs, rising from chair)
• Dermatomyositis: Heliotrope rash, Gottron's papules
• May be paraneoplastic (especially dermatomyositis in adults)

Red Flags

• Back pain with neurological deficit — caution: cord compression or cauda equina
• Proximal myopathy with weight loss — consider malignancy-associated myopathy
• Bone pain with hypercalcaemia — myeloma, bony metastases
• CK >10,000 — rhabdomyolysis risk (AKI, hyperkalaemia)

Bedside

• Clinical examination: Gait, proximal power, spine inspection
• Height measurement: Serial — loss >4cm suggests vertebral fractures

Bloods

• Bone profile: Calcium, phosphate, ALP
• Vitamin D (25-OH): <25 nmol/L = deficient, 25-50 = insufficient
• PTH: Elevated in hyperparathyroidism, vitamin D deficiency
• CK: Elevated in myopathy, rhabdomyolysis (can exceed 100,000 in severe cases)
• ESR/CRP: Inflammatory markers
• Myeloma screen: Serum protein electrophoresis, free light chains

Imaging

• DEXA scan: Gold standard for bone density — T-score at hip and spine
• X-ray: Fractures, Paget's disease, lytic lesions
• MRI: Muscle inflammation (myositis), spinal pathology

Special Tests

• FRAX score: Online tool — 10-year fracture probability
• EMG: Myopathic vs neuropathic pattern
• Muscle biopsy: Inflammatory myopathy, dystrophy
• Bone biopsy: Metabolic bone disease confirmation (rarely needed)

Non-pharmacological

• Weight-bearing exercise for bone health
• Falls prevention: Home assessment, balance training, vision correction
• Adequate dietary calcium (>700mg/day) and vitamin D
• Smoking cessation, alcohol moderation

Pharmacological

• Osteoporosis (NICE CG146):
  • First-line: Alendronic acid 70mg once weekly (take on empty stomach, remain upright 30 min)
  • If intolerant: Risedronate 35mg weekly, IV zoledronic acid 5mg annually
  • Denosumab 60mg SC every 6 months (RANKL inhibitor) — second-line
  • Teriparatide 20mcg SC daily for 24 months — severe osteoporosis with fractures
  • Calcium 1g + vitamin D 800 IU daily as adjunct
• Vitamin D deficiency: Loading dose colecalciferol 50,000 IU weekly × 6 weeks, then 800-2000 IU daily maintenance
• Paget's disease: Zoledronic acid 5mg IV single dose (if symptomatic or ALP elevated)

Referral Criteria

• Fragility fracture — fracture liaison service (FLS)
• Suspected inflammatory myopathy — rheumatology
• Suspected myeloma — haematology urgent referral

• Hip fracture: 30-day mortality approximately 6.7%; 1-year mortality ~30%; only ~50% regain pre-fracture mobility
• Osteoporosis treatment: Bisphosphonates reduce hip fracture risk by ~40% and vertebral fracture by ~50%
• Polymyositis: 5-year survival ~80%; worse if associated malignancy or interstitial lung disease (anti-Jo-1)
• Duchenne muscular dystrophy: Wheelchair-dependent by ~12 years; death typically by 20s-30s (respiratory/cardiac failure)
• Paget's disease: <1% risk of osteosarcoma; most patients have normal life expectancy

Bone Metabolism Summary

Types of Collagen