Osteoporosis — Risk Factors, Pathology, Clinical Features, Investigations, Management and Complications

Osteoporosis is a skeletal disease of low bone mass and micro-architectural deterioration of bone tissue, causing bone fragility and increased fracture risk. Operational (WHO) definition: BMD T-score ≤ −2.5 at spine or hip.

It is a major contributor to the global burden of disease and disability; maintenance of musculoskeletal health during ageing is a key determinant of functional ability. The commonest fragility fractures are hip, forearm (Colles') and vertebral.

Indian context: LASI wave 1 shows a high prevalence of low bone mass in adults ≥60 years; ISBMR recommends Indian reference databases, since using Caucasian norms over-diagnoses osteoporosis in Indians.

Non-modifiable: advancing age, female sex, prior fragility fracture, parental hip fracture history, height loss >4 cm.

Modifiable / lifestyle: low BMI, excess alcohol, smoking, immobility, low calcium and vitamin D intake, low protein intake.

Drugs: glucocorticoid therapy (most important), aromatase inhibitors, androgen-deprivation therapy, anticonvulsants, proton-pump inhibitors, thyroxine over-replacement.

Causes of secondary osteoporosis: rheumatoid arthritis, hyperthyroidism, primary hyperparathyroidism, hypogonadism, diabetes, inflammatory bowel disease, anorexia nervosa, organ transplantation, prolonged immobility, COPD, HIV.

Bone mass peaks in the third decade, then declines; ageing causes uncoupling of bone remodelling — osteoclastic resorption exceeds osteoblastic formation, so each remodelling cycle produces net bone loss.

Oestrogen deficiency after menopause increases RANKL and reduces osteoprotegerin, raising osteoclast number, activity and lifespan → accelerated trabecular loss (5–10 years of rapid loss).

Age-related (type II) loss is driven by secondary hyperparathyroidism from vitamin D deficiency and reduced calcium absorption, declining IGF-1/GH, sarcopenia and reduced mechanical loading; affects cortical and trabecular bone.

Structural consequence: trabecular thinning and perforation, loss of connectivity, cortical thinning and increased cortical porosity → disproportionate loss of bone strength relative to loss of bone density.

Osteoporosis itself is asymptomatic ("silent thief") until fracture occurs — the first clinical presentation is usually a low-trauma fracture after a fall from standing height or less.

Vertebral fracture: acute back pain, or painless — presenting as progressive height loss, dorsal kyphosis, protuberant abdomen, reduced rib–pelvis distance, restrictive lung defect and early satiety.

Hip fracture: shortened externally rotated limb, inability to weight-bear; Colles' fracture after fall on outstretched hand; also proximal humerus and pelvic rami fractures.

DXA of spine and hip is the reference standard for diagnosis and for risk stratification (see Q3).

Vertebral fracture assessment (VFA) or lateral spine X-ray if there is height loss or hyperkyphosis — morphometric fractures are frequently silent but strongly predict further fracture.

Baseline biochemistry to exclude secondary causes: serum calcium (8.5–10.5 mg/dL), phosphate, alkaline phosphatase, creatinine and eGFR, full blood count, ESR, 25-OH vitamin D, TSH, and where indicated PTH, testosterone (men), serum/urine electrophoresis, coeliac serology, 24-hour urinary calcium.

Bone turnover markers (serum CTX for resorption, P1NP for formation) — used chiefly to verify compliance with antiresorptive therapy at 3–6 months, not for diagnosis.

Trabecular bone score (TBS) from the DXA image and hip axis length refine FRAX-based risk beyond BMD alone.

Education on osteoporosis, medication, diet and exercise; daily weight-bearing physical activity.

Nutrition: calcium 800–1000 mg/day, protein ≥1 g/kg body weight/day, vitamin D 800–1000 IU/day.

Fall-prevention with supervised progressive strength and balance training — the programme should run for at least 50 hours to reduce falls (effect on fracture risk remains uncertain). (ii) Pharmacological — stratified by fracture risk Risk category Pathy's / ESCEO recommended treatment Low risk Reassurance and lifestyle advice; consider menopausal hormone therapy (MHT) or SERMs (raloxifene, bazedoxifene) High risk Start an inhibitor of bone resorption — oral bisphosphonate (gastro-resistant risedronate improves adherence), IV bisphosphonate, or denosumab Very high risk Anabolic therapy first — teriparatide/biosimilars, abaloparatide or romosozumab — followed by an antiresorptive Very high hip fracture risk (esp. Consider local osteo-enhancement procedure (LOEP) after first hip fracture)

Key efficacy figures (Pathy's): yearly IV zoledronic acid reduces clinical fracture by 33%, vertebral fracture by 77% and peripheral fracture by 25%; give vitamin D beforehand. Adverse effects: acute-phase influenza-like reaction in one in three at first infusion, and a higher incidence of atrial fibrillation than placebo.

Denosumab (anti-RANKL monoclonal antibody, subcutaneous twice yearly) blocks RANKL–RANK binding, inhibits osteoclast development, and reduces vertebral, non-vertebral and hip fractures. Discontinuation causes rebound multiple vertebral fractures — always follow with a bisphosphonate for 1–2 years.

Teriparatide reduces new vertebral and non-vertebral fracture independent of baseline T-score, age and number of fractures; BMD gain is dose-dependent. Romosozumab (anti-sclerostin) for 12 months followed by alendronate produced significantly fewer fractures than alendronate alone (Saag et al.); FDA-approved since April 2019 for postmenopausal women at high fracture risk.

Limitations in the elderly: raloxifene does not reduce femoral neck fracture; MHT is effective but carries breast cancer, thromboembolic, stroke and coronary risk; strontium ranelate raised BMD but caused DRESS and thromboembolism.

Oral bisphosphonates are usually first-line and most cost-effective — NNT to prevent one hip fracture is about 200. In the oldest and frailest, weigh pill burden and comorbidity. Benefits of oral drugs appear at 6–12 months, whereas fall-prevention benefit may be immediate.

Age is not a reason to withhold treatment — unlike cancer screening, the effectiveness of fracture prevention increases with advancing age; economic models suggest treatment is cost-effective with a life expectancy as short as two years. (iii) Follow-up

Assess compliance and side effects; check bone turnover markers at 3–6 months. Review after 3 years of IV or 5 years of oral bisphosphonate, or after any incident fracture: low-risk patients may take a drug holiday for 2 years (reconsider annually); high-risk patients continue.

Fracture Liaison Service (FLS) — a coordinator-based system for the routine assessment and treatment of all postmenopausal women and men after a fragility fracture; benefits are well established and it is the key strategy to close the "treatment gap".

Fracture-related: hip fracture → excess mortality, loss of independence, institutionalisation; vertebral fractures → chronic back pain, kyphosis, restrictive lung disease, GORD and anorexia; distal radius → complex regional pain syndrome.

Treatment-related: bisphosphonates — oesophagitis, hypocalcaemia, acute phase reaction, atrial fibrillation, rare osteonecrosis of the jaw and atypical femoral fracture; denosumab — hypocalcaemia, ONJ, rebound fractures on stopping.