Osteoporosis ✅

Related Subjects: | Bisphosphonates | Osteoporosis | Calcium Physiology | Bisphosphonates | Osteonecrosis of the Jaw

🦴 Osteoporosis is a disorder of reduced bone strength that increases the risk of fragility fracture.
⚠️ Often asymptomatic until fracture occurs, classically affecting hip, vertebrae, and distal radius.
💡 UK practice focuses on identifying those at high fracture risk and implementing prevention or treatment.

ℹ️ About

• Bone strength depends on bone mineral density (BMD) and bone quality/microarchitecture.
• DEXA scan: T-score ≤ -2.5 = osteoporosis, but fragility fracture defines clinical osteoporosis even before imaging.
• Common contributing factors: ageing, menopause, glucocorticoid use, low body weight, smoking, alcohol excess, secondary causes.

WHO Classification (DEXA T-score)

• ✅ Normal: T-score ≥ -1.0
• ⚠️ Osteopenia / Low bone mass: T-score -1.0 to -2.5
• ❌ Osteoporosis: T-score ≤ -2.5
• 💥 Severe / Established osteoporosis: T-score ≤ -2.5 + fragility fracture(s)

🧬 Pathophysiology

• Continuous bone remodelling by osteoclast-mediated resorption and osteoblast-mediated formation.
• Osteoporosis develops when resorption > formation.
• Post-menopause: oestrogen deficiency accelerates osteoclast activity.
• Other contributors: glucocorticoids, immobility, inflammation, endocrine disorders, malnutrition, vitamin D deficiency.

📉 Risk Factors

• Age >50 (risk rises with age)
• Previous fragility fracture
• Parental hip fracture
• Long-term oral glucocorticoids (≥3 months, ≥5 mg prednisolone/day)
• Low BMI / frailty
• Smoking / alcohol excess
• Falls risk
• Premature ovarian insufficiency / hypogonadism
• Secondary causes: hyperthyroidism, hyperparathyroidism, CKD, chronic liver disease, malabsorption, RA, type 1 diabetes

Secondary Osteoporosis Causes

• 💊 Drugs: glucocorticoids, aromatase inhibitors, anti-epileptics, androgen deprivation therapy
• 🦠 Inflammatory disease: RA, IBD, connective tissue disease
• 🧬 Endocrine: hyperthyroidism, hyperparathyroidism, Cushing’s, hypogonadism
• 🔬 Malabsorption / nutrition: coeliac, Crohn’s, vitamin D deficiency, eating disorders
• 🧪 Other: chronic liver disease, CKD, multiple myeloma, immobility

🩺 Clinical Features

• Often asymptomatic until fracture.
• Vertebral fractures: acute/chronic back pain, height loss, kyphosis.
• Fragility fractures: low-trauma fracture of hip, vertebrae, distal radius, pelvis, proximal humerus.
• Older adults may present after a fall or increasing frailty.

🔎 Assessment (UK practice)

• Do not routinely arrange DEXA first.
• Use FRAX or QFracture to assess 10-year fracture risk (without BMD initially).
• DEXA considered if risk is near intervention threshold or to guide treatment decisions.
• In adults >80 years, interpret 10-year risk cautiously; consider short-term fracture risk.

🧮 FRAX® 10‑Year Fracture Risk Calculator (UK)

Estimate the 10‑year probability of major osteoporotic fracture and hip fracture using the official UK FRAX tool:

💡 Notes:

• FRAX uses age, sex, BMI, prior fracture, family history, smoking, glucocorticoids, RA, secondary osteoporosis, alcohol. BMD optional.
• In patients >80y, FRAX may underestimate short-term fracture risk; clinical judgment is essential.
• Repeat FRAX assessment if significant changes in health status, medications, or new fracture occurs.

🔬 Investigations

• FRAX / QFracture: fracture risk tool
• DEXA scan: measure BMD if indicated
• Bloods: FBC, U&E, LFTs, bone profile (Ca, PO4, ALP), vitamin D, TFTs; consider PTH, myeloma screen, coeliac screen
• X-rays / vertebral imaging: if fracture suspected
• Falls assessment: essential in older adults

💊 Management

• Lifestyle: stop smoking, reduce alcohol, weight-bearing & strengthening exercise, optimise nutrition, minimise falls risk
• Calcium & vitamin D: ensure adequacy; supplement if dietary intake inadequate
• Treat underlying causes: vitamin D deficiency, thyrotoxicosis, hypogonadism, malabsorption, glucocorticoid excess
• Bone-protective treatment: for people at sufficiently high fracture risk, per UK NICE guidance

First-Line Drug Treatment

• Oral bisphosphonates: alendronate 70 mg once weekly or risedronate 35 mg once weekly
• Mechanism: inhibit osteoclast-mediated bone resorption → reduced fracture risk
• Administration: fasting, water only, remain upright 30–60 min to avoid oesophagitis
• Alternatives if oral not tolerated: IV bisphosphonate (zoledronic acid), denosumab, specialist therapies

Denosumab

• Anti-RANKL monoclonal antibody: 60 mg SC every 6 months
• Used when bisphosphonates unsuitable
• Check & correct hypocalcaemia before starting
• Caution in severe renal impairment
• Do not stop or delay: rebound bone loss → multiple vertebral fractures

Other Drug Options

• Zoledronic acid IV yearly: alternative if adherence / GI intolerance
• Raloxifene: postmenopausal women; reduces vertebral fracture, increases VTE risk
• Teriparatide, abaloparatide, romosozumab: specialist therapy for very high fracture risk
• HRT: reduces fracture risk; mainly chosen for menopause symptom management

🌸 HRT and Bone

• Transdermal HRT preferred if fracture prevention is considered; lower VTE risk than oral
• Oral HRT increases VTE risk
• Individualised choice per menopause guidance

Glucocorticoid-Induced Osteoporosis

• Fracture risk rises rapidly; do not rely solely on DEXA
• Assess fracture risk formally in patients on long-term steroids
• Consider bone protection early; review steroid dose, falls risk, calcium/vit D, secondary contributors

⚠️ Complications of Treatment

• Bisphosphonates: oesophagitis, GI upset, hypocalcaemia, rare osteonecrosis of the jaw (ONJ), rare atypical femoral fracture
• Denosumab: hypocalcaemia, skin infection, ONJ, atypical femoral fracture, rebound vertebral fractures if stopped/delayed
• Always check calcium/vitamin D status before antiresorptive therapy; consider dental review

Exam Tips 🎓

💡 Fragility fracture = fracture after low-trauma injury
💡 In UK practice, FRAX/QFracture is used before DEXA
💡 Bisphosphonates are usually first-line
💡 Denosumab should not be stopped abruptly
💡 Think of osteoporosis as a fracture-risk problem, not just a low T-score

References

• NICE CG146: Osteoporosis - assessing the risk of fragility fracture
• NICE CKS: Osteoporosis - prevention of fragility fractures
• BNF (NICE): Denosumab
• NICE NG23: Menopause - identification and management
• FRAX® UK tool