Low Bone Mass | Fragility Fractures | DEXA Diagnosis
- DEXA T-score: At or below -2.5 = osteoporosis. -1.0 to -2.5 = osteopenia. Use femoral neck.
- Fragility Fracture: Low-energy fracture = clinical osteoporosis, treat regardless of DEXA
- Bisphosphonates: First-line (alendronate weekly, zoledronic acid yearly) - 40-50% fracture reduction
- Denosumab: Anti-RANKL antibody. CAUTION: Rebound vertebral fractures if stopped
- Anabolics: Teriparatide (PTH analog), romosozumab (anti-sclerostin) for severe disease
- “T-score at or below -2.5 = osteoporosis
- “Fragility fracture = treat regardless of DEXA
- “Bisphosphonates are first-line
- “Hip fracture = 20% 1-year mortality
Any fragility fracture = clinical osteoporosis. Treat regardless of DEXA. Prior fracture is the STRONGEST predictor of future fracture.
Do NOT stop denosumab abruptly. Must transition to bisphosphonate. Stopping causes rapid bone loss and rebound vertebral fractures.
Use for treatment decisions. 10-year fracture risk. Treat if hip fracture risk greater than 3% or major osteoporotic fracture greater than 20%.
FLS reduces re-fracture rate. All fracture patients should be screened and treated. Evidence-based model of care.
- T-score
- At or above -1.0
- Treatment
- Lifestyle: Ca, Vit D, exercise
- Key Action
- Re-screen in 5-10 years
- T-score
- -1.0 to -2.5
- Treatment
- Calculate FRAX
- Key Action
- Treat if FRAX high or risk factors
- T-score
- At or below -2.5
- Treatment
- Bisphosphonate
- Key Action
- First-line pharmacotherapy
- T-score
- Any T-score
- Treatment
- Treat immediately
- Key Action
- FLS referral, bisphosphonate or anabolic
1-25DEXA T-Score Thresholds
Hook:Remember: -1 and -2.5 are the threshold values. Above -1 = Normal, Between = Osteopenia, Below -2.5 = Osteoporosis.
SHATTEREDSecondary Osteoporosis Causes
Hook:SHATTERED bones - check for secondary causes in all young patients or severe disease!
Overview and Epidemiology
Osteoporosis is the most common metabolic bone disease. Hip fracture has 20% 1-year mortality and 50% permanent disability. Every orthopaedic surgeon must screen, investigate, and treat.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to increased bone fragility.
- Prevalence: 200 million affected globally
- Gender: F greater than M (postmenopausal estrogen loss)
- Fractures: 1.5 million fragility fractures/year (US)
- Sites: Vertebra most common, hip most morbid
Osteoporosis is under-diagnosed and under-treated.
- Hip fracture mortality: 20% at 1 year
- Disability: 50% lose independence
- Cost: Enormous healthcare burden
- Second fracture risk: 20% within 1 year
Prevention and treatment save lives.
Pathophysiology and Bone Anatomy
Bone is constantly remodeled by osteoclasts (resorption) and osteoblasts (formation). Osteoporosis results from imbalance favoring resorption. Peak bone mass is achieved by age 30 - after this, net bone loss begins.
- Cortical bone: 80% of skeleton, slow turnover (dense outer layer)
- Trabecular bone: 20% of skeleton, rapid turnover (spongy inner)
- Remodeling cycle: 3-6 months (resorption then formation)
- Estrogen deficiency (postmenopausal): Increased osteoclast activity
- Age-related: Reduced osteoblast function
- Secondary causes: Steroids, hyperthyroidism, hyperparathyroidism
Classification Systems
WHO DEXA Classification
- T-Score
- At or above -1.0
- Interpretation
- Normal bone density
- Action
- Lifestyle measures, rescreen 5-10 years
- T-Score
- -1.0 to -2.5
- Interpretation
- Low bone mass
- Action
- Calculate FRAX, treat if high risk
- T-Score
- At or below -2.5
- Interpretation
- Osteoporosis
- Action
- Pharmacotherapy indicated
- T-Score
- At or below -2.5 + fracture
- Interpretation
- Established osteoporosis
- Action
- Consider anabolic therapy first
T-score compares patient BMD to young adult (20-30 years) mean.
Clinical Assessment
- Prior fracture: Strongest risk factor
- Family history: Hip fracture in parent
- Medications: Steroids, aromatase inhibitors, PPI
- Lifestyle: Smoking, alcohol, low calcium intake
- Menopause: Early menopause (before 45)
- Secondary causes: Thyroid, parathyroid, RA
Comprehensive history identifies high-risk patients.
- Height loss: Greater than 2cm suggests vertebral fracture
- Kyphosis: Thoracic (dowager's hump)
- Rib-pelvis distance: Reduced in vertebral fractures
- Wall-occiput distance: For kyphosis
- Romberg's test: Balance for fall risk
- Timed Up and Go: Functional mobility
Examine for vertebral fractures and fall risk.
Only 30% of vertebral fractures are clinically apparent. Height loss greater than 2cm or new kyphosis should prompt vertebral imaging (lateral spine X-ray or VFA on DEXA).
Investigations
Investigation Protocol
Gold standard for diagnosis. Measure femoral neck AND lumbar spine. Use lowest T-score. Femoral neck preferred for treatment decisions.
10-year fracture probability. Incorporates clinical risk factors. Treat if hip fracture risk greater than 3% or major osteoporotic fracture greater than 20%.
Exclude secondary causes. Calcium, phosphate, vitamin D, PTH, renal function, thyroid function, FBC, LFTs. Consider testosterone in men, celiac serology.
Lateral spine X-ray or VFA. If height loss greater than 2cm or kyphosis. Identifies prevalent vertebral fractures.
DEXA remains the gold standard for osteoporosis diagnosis.
Understanding FRAX: Inputs and Limitations
FRAX is invoked throughout this topic (treat if 10-year hip risk over 3% or major osteoporotic over 20%), but what it actually uses - and, more importantly, what it misses - is never spelled out. The limitations are a favourite higher-mark viva point.
What FRAX is. The WHO FRAX tool computes the 10-year probability of (1) a major osteoporotic fracture (hip, clinical spine, distal forearm or proximal humerus) and (2) a hip fracture, from clinical risk factors with or without femoral-neck BMD - so it can be used even where DEXA is unavailable.
Its clinical inputs:
- Note
- Core demographics
- Note
- One of the strongest factors
- Note
- Family history
- Note
- Yes/no
- Note
- Yes/no (current or recent)
- Note
- A validated secondary cause
- Note
- e.g. type 1 diabetes, hypogonadism, malabsorption
- Note
- Yes/no
- Note
- Improves accuracy; omitted if no DEXA
The limitations (why FRAX can under-estimate risk). Almost all inputs are yes/no, so FRAX is blind to dose and severity:
- It ignores glucocorticoid DOSE - high-dose steroids are under-weighted (adjust upward).
- It ignores the number, recency and site of prior fractures - a recent or vertebral fracture confers very high imminent (near-term) risk that FRAX flattens.
- It does not capture falls, the dominant driver of hip fracture in the very old.
- It uses femoral-neck BMD only, not the lumbar spine - discordant low spine BMD can be added with the trabecular bone score (TBS).
- It is not validated in patients already on treatment.
FRAX gives the 10-year probability of a major osteoporotic and a hip fracture from clinical risk factors +/- femoral-neck BMD (so it works without DEXA). The exam point is its blind spots: because most inputs are yes/no it under-weights steroid dose, the number/recency/site of prior fractures (imminent risk), falls, and lumbar-spine BMD - so clinical judgement must override a "reassuring" FRAX when these are present.
Differential Diagnosis of Low Bone Mass / Fragility Fracture
Low BMD or an apparently fragility fracture is not always primary osteoporosis. Distinguish these mimics — they change management entirely.
- Key discriminator
- Low BMD, normal biochemistry, fragility fracture
- Calcium / Phosphate / ALP
- Normal Ca, PO4, ALP
- Action
- Antiresorptive or anabolic
- Key discriminator
- Bone pain, proximal myopathy, Looser zones
- Calcium / Phosphate / ALP
- Low/normal Ca, low PO4, high ALP, low vitamin D
- Action
- Correct vitamin D / phosphate first
- Key discriminator
- Cortical (forearm) bone loss, stones, fatigue
- Calcium / Phosphate / ALP
- High Ca, low PO4, high PTH
- Action
- Treat parathyroid disease
- Key discriminator
- Lytic lesions, pathological fracture, weight loss
- Calcium / Phosphate / ALP
- High Ca, high ALP if blastic, raised ESR/paraprotein
- Action
- Biopsy / oncology workup
- Key discriminator
- Bone deformity/expansion, isolated high ALP
- Calcium / Phosphate / ALP
- Normal Ca/PO4, markedly high ALP
- Action
- Bisphosphonate for active disease
- Key discriminator
- Young patient, blue sclerae, family history
- Calcium / Phosphate / ALP
- Normal biochemistry
- Action
- Genetic / specialist; bisphosphonates
Before labelling low BMD as osteoporosis, check biochemistry. A high ALP, low phosphate or high calcium should redirect the workup. An unexpected pathological fracture in a patient with weight loss demands exclusion of myeloma and metastasis.
Management Algorithm
Non-Pharmacological Management
Lifestyle Interventions
Calcium 1000-1200mg/day. Vitamin D 800-2000 IU/day. Food sources preferred. Supplement if inadequate.
Regular weight-bearing and resistance exercise. Improves BMD and reduces falls. Walking, dancing, strength training.
Fall prevention program. Home hazard assessment, vision check, medication review, balance training.
Smoking cessation. Limit alcohol (less than 2 drinks/day). Maintain healthy body weight.
Lifestyle measures are the foundation for ALL patients.
BRADOsteoporosis Treatment Ladder
Hook:BRAD treats osteoporosis: Bisphosphonates first, RANKL inhibitors, Anabolics for severe, D+Calcium always!
Treatment Sequencing: Why Anabolic-First
The management tabs and controversies repeatedly state that "gains are larger when an anabolic precedes an antiresorptive", but never explain why - yet the order of drugs is one of the most important modern concepts and the basis of the ARCH trial and the ESCEO/AACE "very high risk" pathway.
Two classes, opposite mechanisms.
- Anabolics (teriparatide [PTH 1-34], romosozumab [anti-sclerostin]) build new bone. Their effect is front-loaded and wanes over roughly 12-24 months - the so-called anabolic window. (Romosozumab is dual-action: it simultaneously increases formation and decreases resorption.)
- Antiresorptives (bisphosphonates, denosumab) preserve bone by suppressing osteoclasts.
Why anabolic-FIRST, then antiresorptive:
- Building bone first, then giving an antiresorptive, consolidates ("locks in") the newly formed bone - producing larger, more durable BMD and strength gains.
- Giving a potent antiresorptive first blunts the subsequent anabolic response: teriparatide works less well, and more slowly, when it follows prior bisphosphonate or denosumab (which have suppressed the remodelling that the anabolic acts on).
- Critically, anabolic gains are lost if not followed by an antiresorptive - like the denosumab rebound principle, you must always consolidate an anabolic course with a bisphosphonate or denosumab.
This is exactly what ARCH showed: romosozumab-then-alendronate beat alendronate-throughout for fracture reduction in high-risk women.
In a very-high-risk patient, sequence matters: give the anabolic first (teriparatide or romosozumab), then always follow with an antiresorptive to consolidate the gains. Doing it the other way round (antiresorptive first) blunts the later anabolic response, and stopping an anabolic without consolidation loses the benefit. ARCH (romosozumab-then-alendronate beating alendronate alone) is the trial to quote.
Surgical Technique
Cement Augmentation for Osteoporotic Bone
- PMMA cement around screws in osteoporotic bone
- Increases pullout strength 2-3x
- Useful in spine and periarticular fractures
- Cement injection into vertebral body
- For painful vertebral compression fractures
- Kyphoplasty restores some height
Augmentation techniques improve fixation in osteoporotic bone.
Complications
- Risk
- 1 in 10000 to 1 in 100000
- Management
- Dental check before starting. Stop if surgery.
- Risk
- Less than 1 in 1000 per year
- Management
- Monitor for thigh pain. Drug holiday after 5 years.
- Risk
- 10-20%
- Management
- Take fasting with water. Consider IV.
- Risk
- Severe if stopped
- Management
- NEVER stop abruptly. Transition to bisphosphonate.
- Risk
- Signal in ARCH trial
- Management
- Avoid if recent MI/stroke.
ONJ and atypical fractures are rare but serious. Benefits of treatment far outweigh risks for patients with osteoporosis.
Postoperative Care
Post-Fracture Osteoporosis Management
Treat the fracture appropriately. Ensure adequate fixation in osteoporotic bone.
DEXA if not done. Laboratory workup for secondary causes. Refer to FLS if available.
Start bisphosphonate or anabolic. Zoledronic acid can be given 2 weeks post-fracture. Ensure adequate calcium and vitamin D.
Monitor DEXA at 2-3 years. Assess for new fractures. Consider treatment modification if not responding.
Fracture Liaison Service (FLS) is the evidence-based model ensuring all fracture patients are investigated and treated.
Outcomes and Prognosis
Fracture Risk Reduction:
- Bisphosphonates: 40-50% hip and vertebral fractures
- Denosumab: 40-70% fracture reduction
- Teriparatide: 65% vertebral, 50% non-vertebral
- Romosozumab: 70%+ vertebral fracture reduction
Prognosis After Hip Fracture:
- Rate
- 20%
- Rate
- 50%
- Rate
- 20%
- Rate
- 5-10%
Early treatment prevents second fractures and mortality.
Guidelines, Registries & Global Practice
Global Epidemiology:
- An estimated 500 million people worldwide have osteoporosis; roughly 1 in 3 women and 1 in 5 men over 50 will sustain a fragility fracture
- Lifetime hip-fracture risk approaches that of breast cancer in women; the global hip-fracture burden is projected to rise sharply with population ageing, with the largest increases in Asia
- Bone mineral density thresholds (T-score) are universal, but fracture incidence varies by region (higher in Northern Europe/Scandinavia, lower in parts of Africa and Asia), reflecting genetics, body habitus, vitamin D status and fall rates
Major Guidelines — Side by Side:
- Treatment threshold
- T-score at or below -2.5, prior hip/vertebral fracture, or high FRAX
- First-line
- Bisphosphonate; anabolic first if very high risk
- Notable position
- Risk-stratified ('very high risk') pathway favouring anabolic-first sequencing
- Treatment threshold
- FRAX-based intervention thresholds (age-dependent)
- First-line
- Oral bisphosphonate (alendronate/risedronate)
- Notable position
- FRAX integrated into thresholds; anabolic for very high risk
- Treatment threshold
- FRAX or QFracture above intervention threshold
- First-line
- Alendronate / risedronate
- Notable position
- Health-economic appraisal drives sequencing; romosozumab via technology appraisal
- Treatment threshold
- FRAX-based; 'very high risk' category
- First-line
- Bisphosphonate or anabolic by risk
- Notable position
- Champions anabolic-first then antiresorptive in very high risk
- Treatment threshold
- Fragility fracture = treat
- First-line
- Antiresorptive plus FLS pathway
- Notable position
- Surgeon-led case-finding and bone health after fracture
Across all major bodies the core message is consistent: a fragility fracture warrants treatment irrespective of BMD, FRAX (or QFracture) guides therapy in osteopenia, and bisphosphonates remain first-line for most, with anabolic-first sequencing reserved for very high risk.
- National hip-fracture registries/audits (UK National Hip Fracture Database, Australian and New Zealand Hip Fracture Registry, and similar programmes) consistently link timely surgery, orthogeriatric co-care and bone-health assessment to lower mortality and re-fracture
- Capture–the–Fracture (IOF) benchmarks FLS programmes internationally
- Well-resourced settings: DEXA, FRAX, FLS, and access to denosumab and anabolics (teriparatide, romosozumab) are standard
- Limited-resource settings: DEXA may be scarce — diagnosis relies on fragility-fracture history and clinical risk; generic oral/IV bisphosphonates and calcium/vitamin D form the backbone; FRAX can be used without BMD input
- Failure to investigate and treat after a fragility fracture is a recognised care gap and a medicolegal exposure worldwide
- Document the osteoporosis discussion and FLS/bone-health referral for every fragility-fracture patient
Controversies and Areas of Uncertainty
Trials (ARCH, and teriparatide-then-antiresorptive data) and ESCEO/AACE favour an anabolic-first sequence in very high risk patients, because gains are larger when an anabolic precedes an antiresorptive. The threshold defining 'very high risk', and cost, remain debated.
Rebound after stopping denosumab is established, but the best transition (timing of zoledronic acid, single vs repeated dosing, role of bone-turnover markers) is not fully settled. Most guidance gives a bisphosphonate around 6 months after the last denosumab dose.
Bisphosphonate holidays balance falling atypical-fracture risk against rising fracture risk. There is no validated tool to time resumption; decisions rest on BMD, fracture history and clinical judgement. Denosumab and anabolics have no holiday concept.
Routine supplementation in community-dwelling, replete adults gives uncertain fracture benefit and a debated cardiovascular/renal-stone signal. Value is clearest in deficient or institutionalised populations and as an adjunct to active drug therapy.
FRAX-guided treatment of osteopenia is widely endorsed, yet the cost-effective threshold varies by country. Evidence in the very old and those with limited life expectancy is thinner, favouring agents with rapid benefit such as zoledronic acid.
The excess cardiovascular events versus alendronate in ARCH (not seen versus placebo in FRAME) remain incompletely explained. Regulators advise avoiding romosozumab within 12 months of MI or stroke; the underlying mechanism is unresolved.
MCQ Practice Points
Q: What T-score defines osteoporosis? A: At or below -2.5. T-score -1.0 to -2.5 is osteopenia. At or above -1.0 is normal.
Q: What is the first-line pharmacological treatment for osteoporosis? A: Bisphosphonates (oral alendronate or IV zoledronic acid). 40-50% fracture reduction.
Q: What is the risk of stopping denosumab abruptly? A: Rebound vertebral fractures. Rapid bone loss occurs. MUST transition to bisphosphonate.
Q: What is the 1-year mortality after hip fracture? A: Approximately 20%. 50% lose independence. Second fracture risk is very high.
Q: When should a bisphosphonate drug holiday be considered? A: After 5 years of oral or 3 years of IV therapy if not high-risk. Monitor for atypical fracture risk. Resume if new fracture.
Q: When should FRAX be used? A: In osteopenia (T-score -1.0 to -2.5) to determine treatment threshold. Treat if 10-year hip fracture risk at or above 3% or major osteoporotic fracture risk at or above 20%.
Exam Viva Scenarios
Practise clinical reasoning and management decisions out loud
“A 75-year-old woman is in hospital following ORIF for intertrochanteric hip fracture from a simple fall. How do you manage her osteoporosis?”
“A 68-year-old woman has a DEXA showing T-score -2.1 at femoral neck and -2.8 at lumbar spine. She has no prior fractures. How do you interpret this and what is your management?”
“A patient on denosumab for 3 years wants to stop treatment. Her last injection was 7 months ago (1 month overdue). What are your concerns and management?”
Diagnosis
- DEXA T-score at or below -2.5 = osteoporosis
- Fragility fracture = clinical osteoporosis
- FRAX for treatment decision in osteopenia
- Exclude secondary causes (bloods)
Treatment
- Calcium 1000-1200mg + Vitamin D 800-2000 IU
- Bisphosphonates first-line
- Denosumab if bisphosphonate fails/contraindicated
- Anabolics for severe disease
Key Drugs
- Alendronate: Oral weekly
- Zoledronic acid: IV yearly
- Denosumab: SC 6-monthly (rebound risk)
- Teriparatide/Romosozumab: Anabolic
Complications
- ONJ: Rare (1 in 10000+)
- Atypical fracture: Drug holiday after 5 years
- Denosumab rebound: Must transition to bisphosphonate
- GI upset with oral bisphosphonates (take upright)
Post-Fracture
- All fragility fractures need treatment
- FLS referral
- Start treatment 2 weeks post-op
- 20% 1-year mortality hip fracture
Evidence Base
- 2027 postmenopausal women with low femoral-neck BMD and at least one existing vertebral fracture; alendronate vs placebo over 36 months
- New morphometric vertebral fracture 8.0% vs 15.0% (RR 0.53)
- Hip fracture relative hazard 0.49 and wrist 0.52
- Any clinical fracture relative hazard 0.72
- 7765 women (mean age 73); once-yearly IV zoledronic acid 5mg vs placebo over 3 years
- Morphometric vertebral fracture reduced 70% (3.3% vs 10.9%; RR 0.30)
- Hip fracture reduced 41% (1.4% vs 2.5%; HR 0.59)
- Serious atrial fibrillation more frequent with zoledronic acid (50 vs 20 patients)
- 7868 women (age 60-90, T-score -2.5 to -4.0); denosumab 60mg SC 6-monthly vs placebo over 36 months
- New vertebral fracture reduced 68% (2.3% vs 7.2%; RR 0.32)
- Hip fracture reduced 40% (0.7% vs 1.2%; HR 0.60)
- Nonvertebral fracture reduced 20%; no ONJ cases in the pivotal trial
- 4093 postmenopausal women with osteoporosis and a fragility fracture; 12 months romosozumab then alendronate vs alendronate throughout
- New vertebral fracture at 24 months reduced 48% (6.2% vs 11.9%)
- Hip fracture reduced 38% (2.0% vs 3.2%); clinical fracture reduced 27%
- More adjudicated serious cardiovascular events in year 1 with romosozumab (2.5% vs 1.9%)
- 1637 postmenopausal women with prior vertebral fractures; teriparatide (PTH 1-34) 20 or 40mcg daily vs placebo (median 21 months)
- New vertebral fracture 5% (20mcg) vs 14% placebo (RR 0.35)
- New nonvertebral fragility fracture reduced ~50% (RR 0.47)
- Lumbar spine BMD increased markedly; only minor side effects (nausea, headache)
- 74 controlled studies (16 RCTs, 58 observational) of FLS vs usual care
- BMD testing 48.0% vs 23.5%; treatment initiation 38.0% vs 17.2%; adherence 57.0% vs 34.1%
- Re-fracture absolute risk reduced ~5 percentage points (13.4% to 6.4% unweighted)
- Mortality reduced ~3 percentage points (15.8% to 10.4% unweighted)