Key Facts

Osteoporosis is extremely common and underdiagnosed. Fragility fractures cause significant morbidity and mortality. FRAX assessment guides who needs DEXA and treatment. Bisphosphonates are the cornerstone of pharmacological management.

Epidemiology

~3 million people in UK. ~500,000 fragility fractures/year. Hip fractures: ~70,000/year in UK (major healthcare burden). Vertebral fractures often asymptomatic (~70% undiagnosed). Lifetime risk: women ~50%, men ~20%.

Aetiology

Primary: age-related bone loss (peak bone mass at ~30; gradual decline thereafter; accelerated loss post-menopause due to oestrogen deficiency). Secondary causes (important to exclude): corticosteroids (commonest secondary cause), hyperthyroidism, hyperparathyroidism, hypogonadism (including premature menopause, androgen deprivation therapy), coeliac disease, inflammatory bowel disease, RA, myeloma, T1DM, chronic liver disease, chronic kidney disease, hyperprolactinaemia, eating disorders.

Pathophysiology

Imbalance between osteoclast (bone resorption) and osteoblast (bone formation) activity → net bone loss. Oestrogen deficiency: major driver in post-menopausal women (oestrogen normally inhibits osteoclast activity via RANK-RANKL-OPG pathway). Corticosteroids: inhibit osteoblasts, increase osteoclast activity, reduce calcium absorption, cause secondary hypogonadism.

Often Asymptomatic Until Fracture

• Loss of height (vertebral fractures)
• Kyphosis (thoracic vertebral wedge fractures)
• Back pain (vertebral compression fracture)

Fragility Fractures (Commonest Sites)

• Vertebral (commonest overall — many asymptomatic): thoracic/lumbar; acute back pain; loss of height; kyphosis
• Hip (proximal femur): most serious; falls in elderly; significant mortality
• Wrist (distal radius — Colles fracture): often earliest fracture type
• Also: proximal humerus, pelvis, ribs

Features of Secondary Causes

• Corticosteroid use: Cushingoid features
• Hyperthyroidism: weight loss, tachycardia
• Coeliac disease: diarrhoea, weight loss, anaemia
• Myeloma: bone pain, anaemia, renal failure

Red Flags

• Fragility fracture at any site → assess and treat for osteoporosis
• Young person with osteoporosis → investigate secondary causes
• Multiple vertebral fractures → consider myeloma, metastases

Fracture Risk Assessment

• FRAX or QFracture: 10-year probability of major osteoporotic fracture and hip fracture
• Use to guide DEXA referral (NICE CG146 — NOGG thresholds)

DEXA Scan (Gold Standard)

• T-score: comparison with young adult mean BMD
  • Normal: T-score ≥ −1.0
  • Osteopenia: T-score −1.0 to −2.5
  • Osteoporosis: T-score ≤ −2.5
  • Severe osteoporosis: T-score ≤ −2.5 + fragility fracture
• Sites: lumbar spine (L1-L4) and proximal femur

Bloods (Exclude Secondary Causes)

• FBC, ESR/CRP: myeloma, inflammatory disease
• Calcium, phosphate, ALP: hyperparathyroidism, osteomalacia
• 25-OH vitamin D: deficiency
• TFTs: hyperthyroidism
• U&Es, LFTs: renal/liver disease
• Testosterone (men), LH/FSH: hypogonadism
• Coeliac screen (tTG antibodies)
• Protein electrophoresis: myeloma
• Bone profile

Imaging

• Spinal X-ray (T4-L4): vertebral fracture assessment if height loss >4cm or kyphosis
• VFA (Vertebral Fracture Assessment): can be done with DEXA

Non-Pharmacological

• Weight-bearing exercise (walking, resistance training)
• Falls prevention: home assessment, vision correction, medication review
• Smoking cessation
• Moderate alcohol intake
• Adequate dietary calcium (700-1200mg/day) and vitamin D

Calcium and Vitamin D

• Calcium 1000mg/day + vitamin D 800 IU/day (e.g., Adcal-D3 One BD): foundation for all patients
• Ensure vitamin D sufficiency (>50 nmol/L)

Bisphosphonates (First-Line — NICE CG146)

• Alendronate 70mg PO weekly: first-line
• Take on empty stomach with full glass of water; remain upright for 30 minutes (oesophageal ulceration risk)
• Risedronate 35mg PO weekly: alternative
• IV zoledronic acid 5mg annually: if oral bisphosphonates not tolerated/contraindicated; also first-line for hip fracture patients (NICE TA464)
• Duration: treat for 5 years (oral) or 3 years (IV zoledronate); then reassess (drug holiday if T-score > −2.5 and no recent fracture)
• Side effects: GI (oral), flu-like reaction (IV), osteonecrosis of jaw (rare — <1 in 10,000), atypical femoral fractures (very rare with prolonged use)

Second-Line/Specialist

• Denosumab 60mg SC 6-monthly (NICE TA204): RANKL inhibitor; cannot take drug holiday (rebound bone loss/vertebral fractures on discontinuation — must transition to bisphosphonate)
• Teriparatide 20μg SC daily × 24 months (NICE TA161): recombinant PTH; anabolic; for severe osteoporosis (T-score ≤−4, or ≤−3.5 + 2 fractures); specialist initiation
• Romosozumab 210mg SC monthly × 12 months (NICE TA876): anti-sclerostin antibody; anabolic then anti-resorptive; for severe osteoporosis; followed by bisphosphonate
• HRT: effective for prevention in post-menopausal women (particularly <60 years); discuss benefits/risks
• Raloxifene: SERM; reduces vertebral fractures; increases VTE risk

Glucocorticoid-Induced Osteoporosis

• Assess fracture risk in ALL patients starting ≥7.5mg prednisolone for ≥3 months
• Consider treatment (bisphosphonate) at lower FRAX thresholds
• NICE TA464: IV zoledronate for glucocorticoid-induced osteoporosis

Referral Criteria

• Rheumatology/metabolic bone service: complex osteoporosis, treatment failure, secondary causes
• Orthogeriatrics: hip fracture
• Falls clinic: recurrent falls

Hip fracture mortality: ~10% at 1 month, ~30% at 1 year. Only ~50% of hip fracture patients regain pre-fracture mobility. Vertebral fractures: each fracture increases risk of further fractures by 5×. Bisphosphonate treatment reduces fracture risk by ~40-50% (vertebral) and ~20-40% (hip). Orthogeriatric co-management reduces hip fracture mortality by ~20%. Osteoporosis treatment is effective and significantly reduces fracture burden.

DEXA T-Score Classification

Osteoporosis Treatment Ladder

Key Osteoporosis Trials