Key Facts

Osteoporosis is often called the 'silent disease' as it is typically asymptomatic until a fracture occurs. Secondary fracture prevention is critical as the risk of further fracture is highest in the first 2 years.

Epidemiology

• ~3 million people affected in the UK
• ~500,000 fragility fractures/year: hip (~66,000), vertebral (~120,000), wrist (~70,000)
• 1 in 2 women and 1 in 5 men >50 will have a fragility fracture
• Annual cost to NHS: ~£4.4 billion

Aetiology

• Primary: postmenopausal (oestrogen deficiency) and age-related
• Secondary causes: corticosteroid use (≥5mg prednisolone >3 months), rheumatoid arthritis, hyperparathyroidism, hyperthyroidism, hypogonadism, coeliac disease, CKD, eating disorders, alcohol excess, smoking, early menopause (<45)

Pathophysiology

• Bone remodelling imbalance: osteoclast resorption > osteoblast formation
• Oestrogen deficiency: accelerated bone loss at menopause (2-3% per year for 5-10 years)
• RANK-RANKL-OPG pathway: RANKL activates osteoclasts; denosumab is a RANKL inhibitor
• Corticosteroid-induced: reduced osteoblast function, increased osteoclast activity, reduced calcium absorption, increased renal calcium excretion
• Trabecular bone affected first → vertebral crush fractures; cortical bone loss → hip fractures

Typical Presentation

• Often asymptomatic until fracture occurs
• Fragility fracture (from standing height or less)
• Loss of height (vertebral fractures)
• Kyphosis (dowager's hump)
• Back pain (vertebral fracture)

Common Fracture Sites

• Hip (neck of femur)
• Vertebral (thoracic and lumbar)
• Distal radius (Colles' fracture)
• Proximal humerus
• Pelvis

Red Flags

• Fragility fracture (triggers investigation and treatment)
• Height loss >4cm (vertebral fractures)
• Sudden severe back pain (acute vertebral fracture)
• Multiple fractures or fracture at unusual site (<50 or atypical location)
• Long-term corticosteroid use without bone protection

Bedside

• Height measurement (compare to historical; loss >4cm suggests vertebral fractures)
• BMI
• FRAX or QFracture risk assessment

Bloods

• Calcium, phosphate, ALP (bone profile)
• Vitamin D (25-hydroxyvitamin D)
• PTH (if calcium abnormal)
• TFTs, LFTs, U&Es
• FBC, ESR, CRP
• Testosterone (men), oestradiol (premenopausal women)
• Myeloma screen (serum protein electrophoresis) if suspicious
• Coeliac serology (tTG) if suspected

Imaging

• DEXA scan: gold standard for bone density measurement
  • T-score ≤ -2.5 = osteoporosis
  • T-score -1.0 to -2.5 = osteopenia
  • T-score > -1.0 = normal
• Spinal X-ray (thoracic/lumbar): vertebral fracture assessment
• VFA (vertebral fracture assessment): DEXA-based; alternative to X-ray

Special Tests

• FRAX tool: 10-year probability of major osteoporotic fracture and hip fracture
• Bone turnover markers (CTX, P1NP): specialist use for monitoring treatment

Non-pharmacological

• Weight-bearing and resistance exercise
• Falls prevention (as per NICE CG161)
• Smoking cessation
• Reduce alcohol (<14 units/week)
• Dietary calcium (aim 1,000mg total daily intake including supplements if needed)

Pharmacological

• First-line: alendronate 70mg weekly (take on empty stomach, remain upright 30 minutes)
  • Alternative: risedronate 35mg weekly
• Vitamin D: 800-1,000 IU daily (colecalciferol)
• Calcium supplementation: only if dietary intake insufficient (Adcal D3, Calcichew D3)
• If bisphosphonates contraindicated/not tolerated:
  • Denosumab 60mg SC 6-monthly (RANKL inhibitor; FREEDOM trial; must not miss doses — rebound vertebral fractures)
  • Raloxifene 60mg OD (SERM; for postmenopausal vertebral fracture prevention)
• Severe osteoporosis/multiple fractures:
  • Teriparatide 20mcg SC daily (PTH analogue; anabolic; max 2 years; NICE TA161)
  • Romosozumab 210mg SC monthly (anti-sclerostin; 12 months then switch to anti-resorptive)
• Corticosteroid-induced osteoporosis: start bone protection if prednisolone ≥7.5mg daily for ≥3 months (or lower dose with other risk factors)

Surgical/Interventional

• Vertebroplasty/kyphoplasty: for acute painful vertebral fractures not responding to conservative management
• Fracture fixation: for hip and other fragility fractures

Referral Criteria

• Fragility fracture: Fracture Liaison Service (FLS)
• FRAX above treatment threshold: initiate treatment in primary care
• Bisphosphonate intolerance/contraindication: metabolic bone specialist
• Atypical femoral fracture or ONJ (bisphosphonate complications): specialist review
• Pre-menopausal osteoporosis or young men: metabolic bone/endocrine referral

• Alendronate: reduces hip fracture by 40% and vertebral fracture by 50% over 3 years
• Denosumab: reduces hip fracture by 40%, vertebral by 68% (FREEDOM trial)
• Teriparatide: reduces vertebral fracture by 65%
• Hip fracture: 30-day mortality ~8%; 1-year mortality ~30%
• Risk of second fracture is highest in first 1-2 years ("imminent fracture risk")
• Treatment should be reviewed at 5 years (alendronate) or 3 years (zoledronate) — consider drug holiday in low-risk patients

FRAX Risk Factors

Osteoporosis Treatment Summary