Osteoporosis - Assessment, Investigation, and Management

Definition / Overview

Osteoporosis is a systemic skeletal condition characterised by reduced bone mineral density (BMD) and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and susceptibility to fracture. It is among the most clinically significant age-related conditions in Australia, with fragility fractures causing substantial morbidity, loss of independence, and healthcare costs.

Key definitions:

• Fragility fracture: a fracture occurring from a mechanism no greater than a fall from standing height, this is diagnostic of osteoporosis regardless of BMD measurement
• Osteopenia (low BMD): T-score between $-1.0$ and $-2.5$
• Osteoporosis: T-score $\leq -2.5$
• Severe osteoporosis: T-score $\leq -2.5$ with one or more fragility fractures

Epidemiology in Australia:

• Affects approximately 1 in 3 women and 1 in 5 men over age 50
• Hip fracture carries 20-30% one-year mortality
• The majority of osteoporosis-related fractures occur in people who are not yet in the osteoporotic T-score range (osteopenic individuals with other risk factors)

Pathophysiology

Bone is continuously remodelled through a coupling of osteoclast-mediated resorption and osteoblast-mediated formation. Peak bone mass is typically achieved in the late 20s to early 30s. After this, a gradual decline in bone density begins, accelerating significantly around menopause due to oestrogen withdrawal, oestrogen normally suppresses osteoclast activity via the RANK-L pathway.

Mechanisms contributing to bone loss:

• Oestrogen deficiency → upregulation of RANK-L → increased osteoclast recruitment and activity → net bone resorption
• Ageing → reduced osteoblast activity and impaired calcium absorption
• Secondary causes (see below) → superimposed on age-related loss
• Reduced peak bone mass in youth (nutrition, genetics, inactivity) → lower "reserve"

The structural consequence is thinning of cortical bone and loss of trabecular connectivity, preferentially affecting the vertebral bodies, femoral neck, distal radius, and proximal humerus, the classic fragility fracture sites.

Risk Factors

Non-modifiable

• Age $\geq 65$ years (women), $\geq 70$ years (men)
• Female sex, early menopause ($< 45$ years), oophorectomy
• Family history of hip fracture (first-degree relative)
• Prior fragility fracture (the single strongest predictor of future fracture)
• Ethnicity (lower risk in those of African descent; higher in Asian and Caucasian populations)
• Low body weight / low BMI ($< 19\,\text{kg/m}^2$)

Modifiable

• Smoking
• Excess alcohol ($\geq 3$ standard drinks/day)
• Physical inactivity
• Low calcium or vitamin D intake
• Falls risk (separate but closely linked domain)

Secondary Causes (screen in all men and premenopausal women; common)

Clinical Features / Diagnosis

Osteoporosis is often clinically silent until fracture occurs. The clinical encounter is typically triggered by:

• An incidental fragility fracture (vertebral, wrist, hip, rib)
• Screening prompted by risk factors or age thresholds
• Back pain or loss of height (suggesting vertebral compression fractures)

History

• Fracture history, type, mechanism, age at occurrence
• Risk factor review (modifiable and non-modifiable)
• Falls history, frequency, circumstances, functional impact
• Medications (especially corticosteroids, duration/dose)
• Menstrual/reproductive history in women
• Dietary history, calcium intake estimate
• Review of systems for secondary causes

Examination

• Height (compare to recalled previous height; $> 4\,\text{cm}$ loss suggests vertebral fractures)
• Weight and BMI
• Thoracic kyphosis ("dowager's hump")
• Gait, balance, muscle strength assessment
• Signs of secondary causes (Cushingoid features, thyroid enlargement)

Investigation

DXA Scanning (Dual-Energy X-ray Absorptiometry)

DXA is the reference standard for measuring BMD. It measures areal BMD (g/cm²) of the lumbar spine and proximal femur (femoral neck and total hip), translating results into standardised scores.

T-score: compares an individual's BMD to the mean of a healthy young adult (aged 20-29 years, white female reference population from the NHANES III database). Expressed as standard deviations above or below this mean.

$$T\text{-score} = \frac{\text{Patient BMD} - \text{Reference Young Adult Mean BMD}}{\text{Reference Young Adult SD}}$$

Z-score: compares BMD to an age- and sex-matched reference. Used for reporting in premenopausal women and men aged $< 50$ years. A Z-score $\leq -2.0$ is "low for age" and warrants investigation for secondary causes.

Important DXA caveats:

• Lumbar spine values may be falsely elevated by osteophytes, aortic calcification, or vertebral fractures in elderly patients, use the lowest valid site for diagnosis
• Should be measured on the same machine serially if monitoring treatment response
• Vertebral fracture assessment (VFA) can be performed simultaneously with DXA, with lower radiation than plain X-ray, to identify unsuspected vertebral fractures, if a vertebral fragility fracture is found, treatment is indicated regardless of T-score

MBS-funded DXA indications in Australia:

• Women $\geq 70$ years and men $\geq 70$ years (2-yearly or 5-yearly depending on initial T-score)
• Any person with a low-impact fracture
• Conditions or treatments expected to cause bone loss (e.g. long-term corticosteroids), annual monitoring
• Monitoring in patients on treatment

FRAX, Fracture Risk Assessment Tool

FRAX is a validated online calculator (University of Sheffield) that estimates an individual's 10-year probability of a major osteoporotic fracture (spine, hip, distal forearm, proximal humerus, combined) and hip fracture specifically. It incorporates:

• Age, sex, weight, height
• Prior fragility fracture
• Family history of hip fracture
• Current smoking and alcohol use ($\geq 3$ units/day)
• Glucocorticoid use
• Rheumatoid arthritis
• Secondary osteoporosis causes
• BMD (femoral neck), optional but improves accuracy

Key FRAX limitations:

• Does not incorporate falls risk
• Does not distinguish recent from remote fractures, or single from multiple fractures
• Underestimates risk with very high steroid doses or multiple vertebral fractures
• Should not be used if BMD is already in osteoporotic range with fracture, treat directly

Australian treatment thresholds (per RACGP/Healthy Bones Australia guidance):

• 10-year major osteoporotic fracture risk $\geq 20\%$ → pharmacological treatment recommended
• 10-year hip fracture risk $\geq 3\%$ → pharmacological treatment recommended
• FRAX is most useful in the osteopenic range (T-score $-1.0$ to $-2.5$) to guide who needs treatment beyond lifestyle measures

Additional Investigations (to exclude secondary causes)

Management

Non-Pharmacological (all patients)

Calcium and Vitamin D:

• Adequate calcium intake: target $1{,}200\,\text{mg/day}$ in women $> 50$ years and men $> 70$ years
• Preferred source is dietary (dairy, leafy greens, fortified foods); supplements used to make up shortfall
• Vitamin D: $800{-}1{,}000\,\text{IU/day}$; supplement if serum 25-OH vitamin D $< 50\,\text{nmol/L}$
• Calcium supplements may marginally increase cardiovascular risk, prefer dietary sources

Physical Activity:

• Weight-bearing exercise (walking, resistance training) stimulates bone formation
• Balance and strength training reduce falls risk independently
• Tai Chi has evidence for fall reduction in community-dwelling older adults

Lifestyle modification:

• Smoking cessation
• Alcohol reduction to $< 2$ standard drinks/day
• Avoid prolonged immobility

Falls Prevention (Critical, see dedicated section below)

Pharmacological Management

Indications for starting pharmacotherapy:

• T-score $\leq -2.5$ (osteoporosis)
• Any fragility fracture (regardless of T-score)
• FRAX 10-year major fracture risk $\geq 20\%$ or hip fracture risk $\geq 3\%$ in osteopenic individuals
• Long-term corticosteroid use (prednisolone $\geq 7.5\,\text{mg/day}$ for $\geq 3$ months)

First-Line: Bisphosphonates

Bisphosphonates are synthetic analogues of pyrophosphate that bind to hydroxyapatite in bone and are preferentially taken up at sites of active resorption. They inhibit osteoclast function (by disrupting the mevalonate pathway in nitrogen-containing bisphosphonates), reducing bone turnover and net resorption. The result is improved BMD, better trabecular microarchitecture, and significantly reduced fracture risk.

Oral bisphosphonate administration rules:

• Take on an empty stomach with a full glass of water (200-250 mL)
• Remain upright for at least 30 minutes afterwards
• No food, drink, or other medications for 30-60 minutes
• Poor adherence is a major clinical problem, simplify regimen where possible

Contraindications to bisphosphonates:

• eGFR $< 30{-}35\,\text{mL/min/1.73m}^2$ (especially zoledronate)
• Oesophageal abnormalities (stricture, achalasia), oral forms only
• Hypocalcaemia (must correct before initiating)

Key adverse effects:

• Oesophagitis/upper GI irritation, oral forms; mitigated by correct administration
• Osteonecrosis of the jaw (ONJ): rare; higher risk with IV formulations and in patients on concurrent antiangiogenic therapy; dental review before IV therapy
• Atypical femoral fracture (AFF): rare subtrochanteric/diaphyseal stress fracture; associated with prolonged use ($> 5$ years); presents with prodromal thigh pain; bilateral radiograph if suspected
• Flu-like reaction (acute phase response): occurs in ~30% after first IV infusion of zoledronate; usually self-limiting within 3 days; prehydration and paracetamol reduce severity
• Hypocalcaemia: especially post-zoledronate; ensure adequate vitamin D before IV treatment

Duration and bisphosphonate holiday:

• Review at 3-5 years for oral bisphosphonates, 3 years for zoledronate
• Consider a "drug holiday" (pause of 1-2 years) in lower-risk patients after adequate treatment, AFF risk continues to accumulate with prolonged use
• High-risk patients (multiple fractures, very low BMD) should continue or transition to another agent

Second-Line and Specialist Agents

Important denosumab caveat: Discontinuation without transitioning to a bisphosphonate leads to rapid rebound bone loss and increased vertebral fracture risk, never stop denosumab abruptly without a plan.

Falls Prevention

Falls prevention is as important as pharmacotherapy in reducing fracture risk because most fractures result from falls. Comprehensive assessment should include:

Multifactorial Falls Risk Assessment

• Medications review: sedatives, antihypertensives, anticholinergics, antidepressants, benzodiazepines, deprescribe where safe
• Visual acuity: refer for optometry/ophthalmology; correct refractive error and cataracts
• Cardiovascular: postural hypotension (active stand BP), arrhythmia
• Neurological: peripheral neuropathy, cerebellar ataxia, Parkinson's, cognitive impairment
• Musculoskeletal: lower limb weakness, painful joints, foot problems, footwear assessment
• Environmental: home hazards, loose rugs, poor lighting, bathroom grab rails, step hazards

Interventions with Evidence

• Exercise programs: progressive resistance and balance training (e.g. Otago program), reduce falls rate by ~35% in community-dwelling older adults
• Tai Chi: proven falls reduction in community-dwelling older adults
• Vitamin D supplementation: reduces falls risk in deficient individuals
• Home hazard modification: occupational therapy home assessment
• Hip protectors: reduce hip fracture risk in residential care when worn correctly, compliance is the limiting factor
• Podiatry: custom footwear and orthotics

Functional Assessment Tools

• Timed Up and Go (TUG): $> 12$ seconds indicates elevated falls risk
• Berg Balance Scale
• 4-Stage Balance Test
• Refer to physiotherapy for formal rehabilitation programs

Complications and Special Considerations

Vertebral Compression Fractures

• Often missed, may present as acute or chronic back pain, or may be asymptomatic
• Loss of vertebral height leads to progressive kyphosis, reduced lung volumes, and abdominal compression
• Acute severe fractures: analgesia, short-term rest then mobilisation; consider vertebroplasty/kyphoplasty in selected patients with refractory pain (specialist decision)
• Even a single morphometric vertebral fracture warrants treatment

Corticosteroid-Induced Osteoporosis

• Risk begins early, even at low doses over weeks
• Prophylactic bisphosphonate should be initiated for anyone expected to be on $\geq 7.5\,\text{mg}$ prednisolone (or equivalent) for $\geq 3$ months
• Ensure calcium and vitamin D adequacy

Men with Osteoporosis

• Often under-recognised and under-treated
• Secondary causes more common, testosterone deficiency, alcohol, corticosteroids
• PBS criteria for treatment exist but differ slightly from women, screen with DXA in men $\geq 70$, or younger with risk factors

Monitoring Response to Treatment

• Repeat DXA at 18-24 months after initiating therapy (MBS-funded annually in high-risk or steroid-induced cases)
• Stable or increasing BMD indicates treatment response
• Bone turnover markers (serum CTX, P1NP) can confirm biochemical response earlier but are not routine in primary care

Long-Term Care and Prevention

Key prescribing reminder: Ensure calcium and vitamin D adequacy before starting any anti-resorptive therapy, hypocalcaemia post-bisphosphonate or denosumab can be clinically significant.

Fracture Liaison Services (FLS) are specialist multidisciplinary programs that systematically identify and manage patients following a fragility fracture, the "second fracture prevention" model. Referral to FLS or initiation of treatment following fragility fracture in the inpatient setting is a core intern responsibility often missed in practice.

Sources

• RACGP Silver Book, Aged care
• Healthy Bones Australia clinical resources
• ANZSGM position statements (Australian and New Zealand Society for Geriatric Medicine)