MRCP Osteoporosis: Mastering FRAX, DXA and Treatment Decisions

Osteoporosis is one of those rare topics that touches geriatrics, endocrinology, rheumatology, renal medicine and prescribing simultaneously - precisely the integrated territory the MRCP thrives on. Part 1 tests T-scores, drug adverse effects and biochemical profiles; Part 2 wraps the same science inside an elderly patient on long-term prednisolone; and PACES occasionally stages the kyphotic woman in Station 5. This guide condenses the UK-relevant guidance - NICE CG146, NICE TA464 and the NOGG guideline - into exam-ready logic you can actually apply under time pressure.

1. Core Definitions That Score Marks Instantly

Key definitions:

• A fragility fracture results from a fall from standing height or less.

• The T-score compares bone mineral density (BMD) with the young adult reference mean; the Z-score compares with age-, sex- and ethnicity-matched peers.

• Use the Z-score in premenopausal women and men under 50. A Z-score of -2.0 or lower is described as 'below expected range for age' and mandates a hunt for secondary causes.

2. UK Numbers Worth Memorising

• Osteoporosis affects over 3 million people in the UK, with more than 500,000 fragility fractures annually.

• Around 70,000 hip fractures occur each year; fragility fractures cost the UK over £4.5 billion including social care.

• Lifetime fracture risk after age 50: roughly 1 in 2 women and 1 in 5 men.

• One-year mortality after hip fracture is approximately 20-30%.

• Only about one-third of vertebral fractures present clinically - the rest are silent, which is why imaging matters.

3. Pathophysiology in 60 Seconds

Oestrogen deficiency increases RANKL and reduces osteoprotegerin, unleashing osteoclast activity and causing trabecular perforation. Ageing adds osteoblast senescence and cortical porosity. Every drug maps onto this biology: bisphosphonates and denosumab are antiresorptives; teriparatide is anabolic; romosozumab blocks sclerostin in the Wnt pathway, delivering both anabolic and antiresorptive effects. Exam questions increasingly reward this mechanism-level understanding.

4. Risk Factors and the Hunt for Secondary Causes

FRAX clinical risk factors: age, sex, low BMI, previous fragility fracture, parental history of hip fracture, current smoking, glucocorticoids, rheumatoid arthritis, secondary causes of osteoporosis, and alcohol (3 units/day or more - note NICE CG146 quotes 4 units/day or more; a classic examiner nuance).

Secondary causes - organise by system:

• Endocrine: thyrotoxicosis, primary hyperparathyroidism, hypogonadism (early menopause under 45, anorexia nervosa, hyperprolactinaemia, androgen deprivation therapy), Cushing syndrome, type 1 diabetes.

• Gastrointestinal: coeliac disease, inflammatory bowel disease, chronic liver disease, bariatric surgery.

• Renal: CKD-mineral bone disorder, renal transplantation.

• Inflammatory: rheumatoid arthritis, ankylosing spondylitis.

• Malignancy: myeloma, bone metastases, systemic mastocytosis.

• Drugs (high-yield list): glucocorticoids (risk begins at prednisolone 2.5 mg/day or more), aromatase inhibitors, GnRH analogues, enzyme-inducing antiepileptics, long-term PPIs, SSRIs, thiazolidinediones, long-term heparin, depot medroxyprogesterone, ciclosporin.

Red flags against 'simple' osteoporosis: presentation under 60, Z-score -2.0 or lower, unexplained weight loss, anaemia, raised ESR/CRP or hypercalcaemia - actively screen for myeloma and other secondary causes.

5. Who to Assess and How (NICE CG146)

• Assess fracture risk in women aged 65 and over, and in men aged 50 and over (and younger women) who have risk factors. Do not assess people already on osteoporosis treatment.

• Use FRAX (can incorporate femoral neck BMD; outputs 10-year major osteoporotic and hip fracture probability) or QFracture (adds dementia, falls and diabetes among its variables but cannot be used with BMD). Do not use both tools on the same patient.

• NOGG interpretation logic: if probability is below the lower assessment threshold, reassure with lifestyle advice and consider reassessing in around 2 years; if intermediate, perform DXA and recalculate; if above the intervention threshold, treat.

• The NOGG intervention threshold equals the fracture probability of a woman of the same age with a prior fragility fracture - the 'fracture begets fracture' principle.

6. Investigations

• DXA is the gold standard: lumbar spine (L1-L4), femoral neck and total hip; report the lowest valid T-score. Use forearm DXA when the spine and hips are unusable (severe obesity, bilateral hip replacement, hyperparathyroidism).

• Vertebral imaging (lateral thoracolumbar radiograph or DXA-based vertebral fracture assessment) when there is kyphosis, height loss greater than 4 cm, new or worsening back pain, or glucocorticoid therapy.

• Baseline bloods in every new diagnosis: FBC, ESR, U&E, LFTs, bone profile (calcium, phosphate, ALP), TSH, 25-OH vitamin D, coeliac serology; testosterone (with LH/FSH and prolactin) in men; paraproteins/immunoglobulins if myeloma is suspected; PTH if hypercalcaemic.

Osteomalacia versus osteoporosis - the biochemical discriminator: osteomalacia shows low calcium, low phosphate, high ALP, secondary hyperparathyroidism and often proximal myopathy; osteoporosis has normal biochemistry.

7. Who You Treat Without Hesitation

• T-score -4.0 or below - treat regardless of risk calculator output.

• Prior vertebral fracture(s) or two or more fragility fractures - treat; NOGG permits commencing treatment without DXA confirmation.

• Fragility hip fracture in older adults - secondary prevention is mandatory; intravenous zoledronate given soon after hip fracture repair reduces subsequent fractures.

8. The Treatment Ladder

Simplified NICE TA464 criteria for alendronate: treat confirmed osteoporosis (T-score -2.5 or below) if the 10-year hip fracture probability is 1% or more and the T-score is -3.5 or below, or the T-score is -2.5 or below with age 70 or over or additional clinical risk factors; treat T-score -4.0 or below irrespective of probability. In real UK practice NOGG thresholds are widely applied, and any prior fragility fracture effectively crosses the line.

Very high risk features (NOGG) - escalates to anabolic therapy: recent fracture within 2 years, multiple fractures, fracture while on treatment, fracture while on glucocorticoids or other bone-harming drugs, T-score below -3.5, high falls risk, or very high calculated fracture probability.

9. Drug Nuances the Examination Loves

10. Prescribing Points for Bisphosphonates

• Correct hypocalcaemia and treat vitamin D deficiency before starting.

• Take in the morning on an empty stomach with a full glass of plain water; remain upright for at least 30 minutes; no food or other tablets for 30 minutes.

• Avoid oral bisphosphonates in oesophageal stricture, achalasia or inability to sit upright.

• Dental review if risk factors for osteonecrosis of the jaw (the risk at osteoporosis doses is under 1 in 10,000; it is far higher with high-dose IV therapy in oncology).

• Over half of patients stop within a year - counselling and planned review are not optional extras.

11. Review and the Drug Holiday

• Review oral bisphosphonates at 5 years and IV zoledronate at 3 years.

• Continue (no holiday) if T-score remains -3.5 or below, prior hip or vertebral fracture, recent fracture, ongoing glucocorticoids, or fracture during treatment (in which case switch class).

• Otherwise institute a drug holiday, exploiting the years of residual skeletal protection.

• Denosumab has no drug holiday concept - it must be continued or formally transitioned.

12. Special Situations

Glucocorticoid-Induced Osteoporosis (Heavily Tested)

• Risk is meaningful from prednisolone 2.5 mg/day; FRAX underestimates risk at doses of 7.5 mg/day or more (glucocorticoid-adjusted FRAX should be used) and overestimates below 2.5 mg/day.

• Everyone aged 40 and over expected to take oral glucocorticoids for 3 months or more warrants risk assessment; ensure calcium and vitamin D adequity.

• Treatment thresholds are lower than for postmenopausal osteoporosis - clinicians commonly treat around a T-score of -1.5 in the context of significant ongoing steroid exposure or an adjusted risk above threshold.

• Prevention options: alendronate and risedronate (both licensed); teriparatide has strong evidence in glucocorticoid-induced bone loss.

• Patients under 40 on 7.5 mg or more for 3 months or more with additional risk factors need DXA and vertebral imaging; a prior fragility fracture mandates treatment.

Men

• Screen for hypogonadism (testosterone, LH, FSH, prolactin). Alendronate first line; zoledronate, denosumab and teriparatide are alternatives.

Premenopausal Women

• Interpret with Z-scores, investigate aggressively for secondary causes, and reserve drug therapy mainly for those with fragility fractures, secondary osteoporosis or glucocorticoid exposure.

Chronic Kidney Disease

• eGFR below 30-35: avoid oral bisphosphonates and zoledronate. Denosumab may be used with meticulous calcium monitoring. Exclude CKD-mineral bone disorder and adynamic bone disease first.

13. After the Fracture: Secondary Prevention

• The Fracture Liaison Service model - identify, investigate, initiate treatment, monitor - is the gold standard after any fragility fracture in over-50s.

• Bundle with a falls package: strength and balance training, home hazard assessment, vision check, footwear, and medication review (deprescribe sedatives and anticholinergics).

• Acute vertebral fractures: adequate analgesia (cautious, short-course opioids; avoid sedatives), early mobilisation and physiotherapy; vertebroplasty or kyphoplasty only for selected patients with persistent severe pain.

14. PACES Snapshot

A Station 5 classic: an older woman with kyphosis and a dowager hump. Look for Cushingoid stigmata, rheumatoid hands, thyroid disease, and steroid-minimising opportunities. The viva almost always drifts to DXA interpretation, FRAX, alendronate counselling or steroid prophylaxis. Structure your counselling: why (fragility fracture predicts future fracture), how (weekly tablet, empty stomach, upright 30 minutes), safety-net (report thigh pain or swallowing difficulty immediately).

15. Ten Traps That Catch Strong Candidates

1. Quoting a T-score when the question demands a Z-score (or vice versa).

2. Ordering DXA to 'confirm' osteoporosis in a patient with prior vertebral fractures - just treat.

3. Letting a denosumab dose slip by months - rebound vertebral fractures.

4. Starting a bisphosphonate with uncorrected vitamin D deficiency or hypocalcaemia.

5. Prescribing oral bisphosphonates with eGFR below 30-35.

6. New thigh pain after 5 years of bisphosphonate - atypical femoral fracture until proven otherwise (image, and check the other femur).

7. Reaching for romosozumab in a patient with recent cardiovascular events.

8. Forgetting raloxifene does not prevent hip fracture and raises VTE risk.

9. Missing myeloma behind 'osteoporosis' when anaemia, high ESR or hypercalcaemia coexist.

10. Assuming QFracture uses BMD (it does not) or ignoring the FRAX versus NICE alcohol threshold difference.

16. Practice Questions

Q1. A 68-year-old woman has a femoral neck T-score of -3.2 and FRAX 10-year hip fracture probability of 1.5%, with no prior fractures. What is the most appropriate first-line treatment?
A) Raloxifene B) Alendronate 70 mg weekly C) Teriparatide D) HRT E) Denosumab

Answer: B. T-score below -2.5 with hip probability at or above 1% satisfies NICE TA464 criteria for first-line oral bisphosphonate. Anabolics are reserved for very high risk.

Q2. A 74-year-old on denosumab for 4 years has her 6-monthly injection delayed by 12 weeks and develops severe back pain; imaging shows new vertebral fractures. What is the mechanism?

Answer: Rebound high-turnover bone loss following delayed or discontinued denosumab. Lesson: denosumab must never be delayed; if stopped, transition to a bisphosphonate.

Q3. A 58-year-old man on prednisolone 10 mg daily for 6 months has a T-score of -1.4. Best management?
A) Vitamin D alone B) Repeat DXA in 2 years C) Alendronate with calcium and vitamin D D) Raloxifene E) Reassure

Answer: C. Glucocorticoid-induced osteoporosis operates at lower treatment thresholds; alendronate plus calcium/vitamin D adequity is standard prophylaxis.

Q4. A 72-year-old on alendronate for 6 years reports months of dull left thigh ache; radiographs show focal thickening of the lateral femoral cortex. Next best step?

Answer: Diagnose atypical femoral fracture - stop the bisphosphonate, image the contralateral femur, consider teriparatide and orthopaedic opinion for incomplete fractures.

Summary Box

• T-score -2.5 or below = osteoporosis; add a fragility fracture and it is severe disease.

• Risk-stratify with FRAX or QFracture (not both); treat NOGG-high and NICE-TA464-qualifying patients.

• Alendronate first line; anabolic-first for very high risk; denosumab must never run late.

• Glucocorticoids lower every threshold - assess everyone on 3 months or more of steroids.

• Always hunt secondary causes and bundle treatment with falls prevention.

Guidance evolves - cross-check the current NICE and NOGG versions before your exam, as thresholds and licensing are periodically updated. Master these principles, and osteoporosis becomes guaranteed marks rather than a fragile performance.