Key Facts

Osteoporosis is characterised by reduced bone mineral density (BMD) and deterioration of bone microarchitecture, resulting in increased bone fragility and susceptibility to fracture.

Epidemiology

• Affects ~3 million people in the UK
• ~500,000 fragility fractures per year in the UK
• ~1 in 2 women and ~1 in 5 men over 50 will sustain a fragility fracture
• Hip fractures: ~76,000/year in the UK; cost NHS ~£2 billion/year

Aetiology

• Primary: postmenopausal (oestrogen deficiency) and age-related
• Secondary: glucocorticoids (>7.5mg prednisolone ≥3 months — most common secondary cause), hypogonadism, hyperthyroidism, hyperparathyroidism, coeliac disease, RA, CKD, myeloma, anorexia, medications (aromatase inhibitors, GnRH analogues, PPIs, SSRIs)

Pathophysiology

• Imbalance between osteoblast (bone formation) and osteoclast (bone resorption) activity
• Oestrogen deficiency → increased osteoclast activity → accelerated bone loss (postmenopausal)
• Glucocorticoids → decreased osteoblast function + increased osteoclast lifespan
• Trabecular bone affected earlier (vertebrae) → cortical bone later (hip)
• RANK/RANKL/OPG system regulates osteoclast differentiation

Typically Asymptomatic Until Fracture

• Often discovered incidentally or after fracture

Fragility Fractures

• Vertebral: acute back pain, loss of height, kyphosis ('dowager's hump')
  • ~Two-thirds are asymptomatic and discovered incidentally
• Hip: fall from standing height, shortened/externally rotated leg
• Distal radius (Colles'): fall on outstretched hand
• Proximal humerus, pelvis, ribs

Red Flags (Suggest Secondary Cause or Alternative Diagnosis)

• Fracture in premenopausal woman or man <50
• Multiple fractures despite treatment
• Very low T-score (<-3.5)
• Young patient with osteoporosis (coeliac, hypogonadism, eating disorder)
• Bone pain without fracture (myeloma, metastases)

Bedside

• Height measurement: serial monitoring (loss >4cm suggests vertebral fractures)
• FRAX score: estimate 10-year fracture risk (includes age, sex, BMI, fracture history, steroids, smoking, alcohol, RA, secondary causes)

Bloods (to exclude secondary causes)

• FBC, ESR: myeloma screen
• Calcium, phosphate, ALP: hyperparathyroidism, osteomalacia, Paget
• 25-OH Vitamin D: deficiency common
• TFTs: hyperthyroidism
• LFTs, U&Es: baseline
• Testosterone (men): hypogonadism
• Coeliac screen: anti-tTG
• SPEP/BJP: myeloma (if ESR raised, unexplained anaemia)
• Bone turnover markers: CTX, P1NP (monitoring treatment response)

Imaging

• DXA scan: gold standard for BMD measurement
  • T-score ≤-2.5: osteoporosis
  • T-score -1.0 to -2.5: osteopenia
  • T-score >-1.0: normal
• Vertebral fracture assessment (VFA): lateral DXA to detect asymptomatic vertebral fractures
• Spinal X-ray: if vertebral fracture suspected

Special Tests

• FRAX/QFracture: 10-year fracture risk assessment; guide treatment initiation
• NOGG algorithm: UK-specific treatment thresholds based on FRAX

Non-pharmacological

• Weight-bearing and resistance exercise
• Falls prevention (home hazard assessment, balance training, vision check)
• Smoking cessation, moderate alcohol
• Calcium 700–1200mg/day (dietary preferred) + vitamin D 800–1000 IU/day

Pharmacological

First-line:

• Alendronate 70mg weekly (oral bisphosphonate; NICE TA464)
• Take on empty stomach with full glass of water, remain upright for 30 minutes

If alendronate not tolerated:

• Risedronate 35mg weekly (oral bisphosphonate)
• Ibandronate 150mg monthly (oral) or 3mg IV quarterly
• Zoledronic acid 5mg IV annually (if oral bisphosphonates not tolerated; NICE TA464)

Second-line:

• Denosumab 60mg SC every 6 months (anti-RANKL; NICE TA204)
  • CRITICAL: do NOT stop abruptly → rebound vertebral fractures; must transition to bisphosphonate

High fracture risk/severe osteoporosis:

• Teriparatide 20mcg SC daily (PTH analogue; anabolic; NICE TA161) — max 2 years
• Romosozumab 210mg SC monthly (anti-sclerostin; NICE TA876) — 12 months then bisphosphonate

Glucocorticoid-induced osteoporosis:

• Start bisphosphonate if ≥7.5mg prednisolone for ≥3 months (NICE TA464 does not require DXA first)

Referral Criteria

• Fracture liaison service: all fragility fractures (secondary fracture prevention)
• Rheumatology/metabolic bone: treatment failure, unusual osteoporosis, young patients
• Orthopaedics: acute hip/vertebral fracture

• Hip fracture 1-year mortality: ~30% (elderly); 30-day mortality: ~8%
• Vertebral fracture: increased mortality (~15% over 5 years); each vertebral fracture increases risk of further fracture 5-fold
• Bisphosphonate treatment reduces hip fracture risk by ~40% and vertebral fracture by ~50–70%
• Treatment gap: ~80% of patients with fragility fractures do NOT receive osteoporosis treatment
• Adherence: ~50% stop bisphosphonates within 1 year
• Atypical femoral fracture: rare complication of long-term bisphosphonate use (~1/10,000/year)

NICE TA464 Treatment Pathway

FRAX Risk Factors