Osteoporosis and fragility fracture prevention

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Osteoporosis is reduced bone strength that makes low-energy fracture more likely. A T-score of −2.5 or lower at the femoral neck, total hip or lumbar spine is a densitometric definition, not the only treatment route. Many fractures occur above that threshold because age, previous fracture, falls, glucocorticoids and bone quality alter risk. Ask about every adult fracture, height loss, new thoracic or lumbar pain, falls, menopause or hypogonadism, steroid dose and duration, parental hip fracture, smoking, alcohol, diet, mobility, gastrointestinal disease, kidney disease, endocrine symptoms and medicines affecting bone.

The immediate objective after a fragility fracture is preventing the next event. A fracture liaison service can identify patients, arrange vertebral and secondary-cause assessment, initiate treatment and verify persistence. FRAX estimates ten-year hip and major osteoporotic fracture probability; current NOGG thresholds distinguish reassurance, DXA refinement, treatment and very-high-risk specialist referral. DXA refines probability where needed, while a recent vertebral or hip fracture often justifies treatment before scanning.

Treatment is a sequence, not an isolated prescription. Choose a drug the person can receive reliably, correct calcium or vitamin-D problems, discuss dental health and rare harms proportionately, and schedule review. Bisphosphonate persistence allows some selected lower-risk patients to pause after reassessment. Denosumab has no comparable residual protection, so timed alternative antiresorption must accompany cessation. An anabolic course also needs immediate consolidation.

Key points

A fragility fracture follows force equivalent to a fall from standing height or less and should trigger prompt risk assessment and secondary prevention.
Use FRAX with clinical risk factors; add femoral-neck DXA when it will refine a decision, but do not delay treatment after a recent high-risk fracture merely to await scanning.
Look for silent vertebral fractures with vertebral-fracture assessment or lateral spine imaging when height loss, kyphosis, acute compatible pain or strong risk warrants it.
Offer oral alendronate or risedronate, or intravenous zoledronate, to many high-risk adults; choice depends on urgency, adherence, swallowing, renal function, preference and contraindications.
Denosumab 60 mg subcutaneously every six months must not be delayed or stopped without planned alternative antiresorption; record the next injection and exit strategy before starting.
Very-high-risk patients, especially after recent or multiple vertebral fractures, need specialist consideration of teriparatide or romosozumab followed promptly by antiresorptive treatment.
Correct hypocalcaemia and material vitamin-D deficiency, ensure adequate dietary calcium and reduce falls, smoking and excess alcohol; supplements alone do not treat high fracture risk.
Review oral bisphosphonates around five years and intravenous zoledronate around three, continuing longer when age, fracture history, glucocorticoids or interval fracture maintain high risk.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Age and hormone loss

Menopause accelerates trabecular loss through oestrogen withdrawal, while ageing reduces osteoblast function, sex hormones, muscle strength, balance and vitamin-D production in all sexes.

Clinical risk exposure

Previous fragility fracture, parental hip fracture, low body weight, smoking, excess alcohol, falls and prolonged immobility increase risk independently or through bone and muscle loss.

Secondary osteoporosis

Glucocorticoids, aromatase inhibitors, androgen deprivation, hypogonadism, hyperthyroidism, hyperparathyroidism, malabsorption, inflammatory disease, kidney or liver disease and haematological disorders require active consideration.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Remodelling imbalance
When osteoclast resorption persistently exceeds osteoblast formation, trabeculae perforate and cortical bone becomes porous, reducing strength beyond the change captured by mineral density alone.
2
Microarchitectural failure
Loss of trabecular connectivity, cortical thinning and accumulated microdamage impair load distribution, allowing a fall from standing height to cause fracture.
3
Imminent refracture risk
A recent fracture identifies vulnerable bone and ongoing falls exposure; another fracture is especially likely over the next two years, making treatment delay clinically important.
4
Medicine-specific biology
Bisphosphonates persist in mineralised bone, denosumab suppression reverses rapidly when dosing stops, and anabolic treatment needs subsequent antiresorption to retain gained bone.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Sentinel fragility fracture

A low-energy hip, vertebral, wrist or proximal-humerus fracture is clinical evidence of skeletal fragility and predicts another fracture.

Silent vertebral disease

Height loss, increasing kyphosis, rib-to-pelvis discomfort or incidental compression may reveal vertebral fractures without a remembered acute event.

Glucocorticoid exposure

Risk rises early and is not fully represented by BMD; record daily dose, cumulative duration, intermittent high-dose courses and expected continuation.

Falls phenotype

Poor balance, sarcopenia, visual impairment, postural hypotension, sedating medicines and environmental hazards can dominate immediate risk despite modest density loss.

Secondary-cause clues

Premature menopause, sexual dysfunction, diarrhoea, weight loss, renal stones, bruising, thyroid signs or inflammatory disease directs additional testing.

Red flags requiring action

Sudden hip or groin pain with inability to bear weight after a low-energy fall may be a hip fracture even when initial radiographs are negative and needs urgent definitive imaging.
Acute back pain with progressive weakness, saddle sensory loss, bladder dysfunction or known cancer requires emergency assessment for cord or cauda-equina compression.
Severe focal night pain, weight loss, anaemia, hypercalcaemia or a monoclonal protein suggests myeloma, metastasis or another secondary process rather than uncomplicated osteoporosis.
Jaw pain with exposed bone or new persistent thigh or groin pain during antiresorptive treatment requires assessment for jaw osteonecrosis or atypical femoral fracture.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line FRAX probabilityFirst stepFirst line
Why
Integrate age and validated clinical factors to decide reassurance, DXA refinement, treatment or specialist referral.
Interpretation and limitations
Enter femoral-neck BMD when available, not lumbar T-score; compare with current NOGG thresholds and apply judgement for falls, dose exposure and recent fracture.
02
DXA hip and lumbar spine
Why
Measure mineral density, refine risk, establish a baseline and help classify discordant or treatment-resistant cases.
Interpretation and limitations
Use the lowest valid site while recognising degenerative spine change can falsely elevate lumbar BMD; T-score above −2.5 does not negate high clinical probability.
03
Vertebral fracture assessment
Why
Find unrecognised compression fractures that materially increase risk and may move care into a very-high-risk pathway.
Interpretation and limitations
Use DXA lateral imaging or spine radiographs for height loss, kyphosis, compatible pain or strong risk; distinguish fracture from degenerative wedging.
04
Secondary-cause screen
Why
Identify correctable disease and establish safety before antiresorptive or anabolic treatment.
Interpretation and limitations
Usually include FBC, ESR or CRP, calcium, phosphate, ALP, renal and liver profile, vitamin D and thyroid tests; add coeliac, PTH, testosterone or monoclonal studies when indicated.
05
Pre-treatment mineral safety
Why
Prevent hypocalcaemia and select a medicine compatible with kidney function and mineral metabolism.
Interpretation and limitations
Correct low calcium and important vitamin-D deficiency before potent antiresorption; severe CKD may represent CKD-mineral bone disorder requiring specialist interpretation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Osteomalacia

Defective mineralisation produces diffuse pain, proximal weakness and raised alkaline phosphatase, often with low phosphate or vitamin D; osteoporosis usually has normal bone biochemistry.

Malignant bone disease

Myeloma or metastasis can cause vertebral collapse and low density but is suggested by disproportionate pain, anaemia, renal dysfunction, hypercalcaemia or destructive lesions.

Endocrine high-turnover disease

Hyperparathyroidism, thyrotoxicosis and Cushing syndrome alter bone turnover; distribution, biochemistry and directed endocrine assessment separate them from primary age-related loss.

Non-fragility fracture

Clarify injury energy and morphology; lesion-centred, high-energy or atypical subtrochanteric fractures need cause-specific investigation rather than automatic fragility classification.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-line risk pathwayTreat without avoidable delayFirst stepFirst lineA fragility fracture, strong clinical risk profile or opportunistic imaging raises osteoporosis concern.

1Confirm fracture mechanism and site, calculate FRAX where appropriate, assess falls and request DXA only when it will refine rather than postpone the decision.
2Search for vertebral fractures and secondary causes, check renal function, calcium and vitamin D, and address nutrition, smoking, alcohol, strength, balance and home hazards.
3Begin an appropriate anti-fracture medicine promptly after recent fracture, documenting administration, duration review and the response to missed doses or discontinuation.
4Use a fracture liaison service where available to connect acute fracture care, primary-care prescribing, adherence and repeat risk review.

02Preferred antiresorptivesMatch delivery to feasibilityPreferredPharmacological treatment is indicated and no feature yet mandates a bone-anabolic specialist sequence.

1Offer weekly oral alendronate or risedronate when fasting and upright administration is feasible and no important oesophageal or renal contraindication exists.
2Use intravenous zoledronate when adherence, swallowing or absorption makes oral treatment unsuitable, after checking eGFR, calcium, vitamin D and hydration.
3Consider denosumab when bisphosphonates are unsuitable, but only after agreeing six-monthly recall and a safe exit plan.
4Judge response through fractures, adherence and risk rather than expecting rapid symptom or large density change.

03Very-high-risk escalationConsider anabolic-first treatmentEscalationRecent or multiple vertebral fractures, very low BMD, fracture during adequate treatment or combined major factors indicate very-high probability.

1Refer promptly to an osteoporosis specialist and verify that osteomalacia, malignancy and severe CKD-mineral disease have been excluded.
2Assess eligibility for teriparatide or, in suitable postmenopausal patients, twelve months of romosozumab after cardiovascular history and licensed criteria review.
3Follow the completed anabolic course immediately with effective antiresorption so acquired density and fracture protection are retained.

04Planned reviewPrevent gaps and reboundA bisphosphonate reaches review duration, denosumab may stop, or an anabolic course ends.

1Recalculate risk, review interval fractures, age, hip BMD, glucocorticoids, falls and adherence; continue longer when residual risk remains high.
2If a lower-risk bisphosphonate user pauses, define reassessment and restart earlier after a new fracture or major risk change.
3AlternativeNever stop or delay denosumab without specialist-supported alternative antiresorption, commonly zoledronate around when the next injection would have been due.
4Begin antiresorptive consolidation promptly after anabolic therapy, accounting for kidney function, calcium status and previous treatment.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

A commonly preferred oral bisphosphonate for high-risk adults when administration and gastrointestinal absorption are reliable.

Alendronic acid

Take 70 mg orally once weekly on waking with at least 200 mL plain water, at least 30 minutes before food, drink or another medicine; remain upright for at least 30 minutes.

Avoid oesophageal emptying disorders, inability to sit upright, hypocalcaemia and creatinine clearance below 35 mL/min. Separate calcium, iron and antacids; avoid in pregnancy and conception planning.

An effective option after hip fracture or when oral bisphosphonate adherence, swallowing or absorption is unsuitable.

Zoledronic acid

Give 5 mg by intravenous infusion over at least 15 minutes once yearly after hydration and mineral assessment; formally review after three annual doses, extending for persistent high risk.

Correct hypocalcaemia and vitamin-D deficiency, check creatinine before each infusion, and avoid creatinine clearance below 35 mL/min; warn about acute-phase symptoms and rare jaw or femur events.

A potent antiresorptive alternative for eligible high-risk adults when bisphosphonates are unsuitable or specialist selection favours it.

Denosumab

Inject 60 mg subcutaneously every six months with adequate calcium and vitamin D; arrange recall before initiation and administer subsequent doses on time without an unplanned gap.

Correct hypocalcaemia and monitor calcium closely in severe renal impairment. Never delay or stop without alternative treatment because rebound vertebral fractures may follow; contraindicated in pregnancy.

Specialist bone-anabolic treatment for selected very-high-risk adults, including some with severe vertebral osteoporosis or antiresorptive failure.

Teriparatide

Inject 20 micrograms subcutaneously once daily for a maximum cumulative 24 months, then commence an antiresorptive without a prolonged gap.

Avoid hypercalcaemia, non-osteoporotic metabolic bone disease, skeletal malignancy, bone irradiation and severe renal impairment; contraindicated during pregnancy and breastfeeding.

Specialist anabolic and antiresorptive therapy for eligible postmenopausal adults with severe osteoporosis and very high fracture risk.

Romosozumab

Give 210 mg subcutaneously once monthly as two consecutive 105 mg injections for 12 months only, then move directly to antiresorptive treatment.

Do not use after myocardial infarction or stroke; assess cardiovascular risk, correct hypocalcaemia and monitor calcium in severe renal disease; contraindicated in pregnancy.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Hip-fracture consequences

Hip fracture causes pain, immobility, delirium, thrombosis, infection, lost independence and substantial mortality; many survivors never regain previous function.

Vertebral fracture burden

Multiple compression fractures cause height loss, kyphosis, chronic pain, restrictive respiratory mechanics, abdominal crowding and greatly increased further-fracture risk.

Discontinuation harm

Unplanned denosumab delay or cessation can cause rebound remodelling and multiple vertebral fractures; ending anabolic treatment without consolidation rapidly loses benefit.

Rare antiresorptive toxicity

Jaw osteonecrosis and atypical femoral fracture are uncommon at osteoporosis doses but require prevention advice, symptom recognition and reassessment of continued treatment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record the next administration and review date at initiation; use recall systems to prevent unintended gaps, especially with denosumab.
Ask about new fractures, falls, height loss, back pain, thigh or groin pain, jaw symptoms, dental procedures, adherence and oral administration technique.
Check calcium, vitamin-D status and renal function before intravenous bisphosphonate or denosumab as appropriate, with earlier post-dose calcium monitoring in severe kidney disease.
Repeat DXA after an interval likely to affect management, often two to three years in treated high-risk disease, using the same valid sites when possible.
Reassess oral bisphosphonate at five years and zoledronate at three; extend treatment for older age, hip or vertebral fracture, glucocorticoids or fracture during treatment.
After denosumab cessation or anabolic completion, verify that planned antiresorptive therapy was actually administered.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Fracture can diagnose risk

A recent hip or vertebral fragility fracture can justify immediate treatment before DXA because waiting exposes the patient during the highest-risk period.

Normal chemistry is expected

Primary osteoporosis usually has normal calcium, phosphate and ALP; abnormal bone chemistry raises osteomalacia, hyperparathyroidism, malignancy or another secondary explanation.

Denosumab needs an ending

Its effect wears off rapidly, unlike retained bisphosphonate in bone; the safest time to design subsequent therapy is before the first injection.

Rare harms need proportion

At osteoporosis doses, jaw osteonecrosis and atypical femur fracture are uncommon, while untreated high fracture risk is frequent and consequential.

Sequence alters benefit

Very-high-risk patients may gain more from early anabolic treatment, but every anabolic course needs antiresorptive consolidation to retain improvement.

11Common pitfallsFrequent interpretation and management errors.

01
Do not wait for DXA after a recent high-risk fragility fracture when the scan would not alter the need for treatment.
02
Do not call calcium and vitamin D complete osteoporosis treatment; they correct substrate but lack adequate anti-fracture efficacy for high-risk disease.
03
Do not prescribe oral alendronate without checking whether fasting, water and upright instructions are feasible.
04
Do not start denosumab without a reliable recall system and named cessation plan, and never substitute an informal drug holiday.
05
Do not call a new fracture pharmacological failure before checking adherence, duration, falls, secondary causes and expected onset of protection.
06
Do not stop antiresorptive treatment solely because dental extraction is planned; coordinate individual fracture and dental risk.