Case 26.5 – Osteoporosis

Definition of osteoporosis:

• Osteoporosis: Systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to increased bone fragility and susceptibility to fracture
• WHO definition (densitometric): Bone mineral density (BMD) T-score of ≤-2.5 at the hip or spine (measured by DEXA scan)
• Clinical definition: "Fragility fracture" - fracture occurring from mechanical forces that would not ordinarily result in fracture (e.g., fall from standing height or less, or spontaneous fracture)
• Most common metabolic bone disease
• Major public health problem - causes significant morbidity, mortality, healthcare costs

Classification:

• Primary osteoporosis:
  • Type I (postmenopausal): Related to estrogen deficiency after menopause; predominantly affects trabecular bone; vertebral and distal radius fractures common
  • Type II (senile/age-related): Occurs in both men and women >70 years; affects cortical and trabecular bone; hip and vertebral fractures common
• Secondary osteoporosis: Due to underlying medical condition or medication (see risk factors below)

Risk factors for osteoporosis:

Non-modifiable risk factors:

• Age: Risk increases with age (bone mass peaks ~30 years, then declines)
• Female sex: Women at higher risk (lower peak bone mass, menopause, longer life expectancy)
• Ethnicity: Caucasian and Asian populations at higher risk than African-Caribbean
• Family history: Parental history of hip fracture (genetic component)
• Previous fragility fracture: Single strongest predictor of future fracture
• Early menopause (\<45 years): Prolonged estrogen deficiency

Modifiable lifestyle risk factors:

• Low BMI (\<19 kg/m²): Less mechanical stress on bones, less adipose tissue (which produces estrogen)
• Smoking: Toxic to osteoblasts, affects estrogen metabolism
• Excess alcohol (\>3 units/day): Toxic to bone, increases fall risk
• Low calcium intake: Inadequate substrate for bone mineralization
• Vitamin D deficiency: Impairs calcium absorption and bone mineralization
• Physical inactivity: Lack of weight-bearing exercise reduces bone formation
• Falls risk: Environmental hazards, balance problems, visual impairment, medications causing sedation/postural hypotension

Medical conditions (secondary osteoporosis):

• Endocrine: Hyperthyroidism, hyperparathyroidism, Cushing's syndrome, hypogonadism (in men), diabetes mellitus (type 1)
• Gastrointestinal: Coeliac disease, inflammatory bowel disease, chronic liver disease, malabsorption syndromes
• Rheumatological: Rheumatoid arthritis, ankylosing spondylitis
• Chronic kidney disease
• Malignancy: Myeloma, metastatic bone disease
• Prolonged immobilization

Medications associated with bone loss:

• Glucocorticoids (most important): Prednisolone ≥7.5mg/day for ≥3 months - causes rapid bone loss
• Proton pump inhibitors (PPIs): Long-term use (especially high dose) may reduce calcium absorption
• Aromatase inhibitors (breast cancer treatment)
• Androgen deprivation therapy (prostate cancer)
• Anticonvulsants (phenytoin, carbamazepine - affect vitamin D metabolism)
• Depot medroxyprogesterone acetate (contraceptive)
• Thyroxine (if over-replacement causing suppressed TSH)
• Heparin (long-term use)

Concerning features in this patient (Mrs. Mitchell):

Major red flags:

• Two fragility fractures: Colles' fracture from fall from standing height + previous vertebral crush fracture from minimal trauma (lifting a box)
  • This strongly suggests underlying osteoporosis
  • Previous fracture is the strongest predictor of future fracture
• Age 68 years: Postmenopausal woman in high-risk age group
• Height loss (2 inches/~5cm): Suggests vertebral compression fractures (height loss >4cm is significant)
• Thoracic kyphosis ("forward stoop"): Typical of multiple vertebral fractures

Additional risk factors present:

• Postmenopausal (menopause age 49): ~19 years of estrogen deficiency
• Family history: Mother with hip fracture and osteoporosis (genetic predisposition)
• Long-term PPI use (5 years): May contribute to reduced calcium absorption
• Low dairy intake: Likely inadequate dietary calcium
• Minimal exercise: Lack of weight-bearing exercise
• Low BMI (21 kg/m²): On lower end of normal, less mechanical loading

Clinical significance:

• This patient has a very high probability of having osteoporosis
• She requires urgent assessment (DEXA scan) and treatment initiation
• She is at very high risk of future fractures, particularly hip fracture, which carries significant morbidity and mortality
• Secondary causes should be excluded (though primary osteoporosis most likely given age and menopause)

Diagnosis of osteoporosis:

Clinical diagnosis:

• Fragility fracture in adults >50 years = osteoporosis (regardless of BMD measurement)
  • Fragility fracture = fracture from fall from standing height or less, or spontaneous fracture
  • Common sites: vertebrae, hip (neck of femur), distal radius (Colles'), proximal humerus
• This patient with 2 fragility fractures has a clinical diagnosis of osteoporosis

Densitometric diagnosis (DEXA scan):

• DEXA (Dual-Energy X-ray Absorptiometry): Gold standard for measuring bone mineral density (BMD)
• Typically measures BMD at:
  • Lumbar spine (L1-L4)
  • Hip (femoral neck and total hip)
• Results reported as:
  • T-score: Number of standard deviations above or below the mean BMD of healthy young adults (age 30)
    • Normal: T-score ≥ -1.0
    • Osteopenia (low bone mass): T-score between -1.0 and -2.5
    • Osteoporosis: T-score ≤ -2.5
    • Severe osteoporosis: T-score ≤ -2.5 + fragility fracture
  • Z-score: Number of SDs above/below mean for age-matched controls (used in premenopausal women, men <50, children)

Indications for DEXA scanning:

• Women ≥65 years, men ≥75 years (screening high-risk groups)
• Fragility fracture (to confirm diagnosis and assess severity)
• Major risk factors:
  • Long-term glucocorticoid use (≥7.5mg prednisolone for ≥3 months)
  • Conditions causing secondary osteoporosis (hyperthyroidism, hyperparathyroidism, malabsorption, etc.)
  • Family history of hip fracture
  • Low BMI (\<19 kg/m²)
• Monitoring response to treatment (repeat DEXA every 2-3 years on treatment)

Investigations to perform in this patient:

1. DEXA scan (essential):

• Although clinical diagnosis of osteoporosis already made (fragility fractures), DEXA still indicated to:
  • Quantify severity of bone loss
  • Provide baseline for monitoring treatment response
  • Assess fracture risk at different sites
• Expected findings: T-score ≤ -2.5 at spine and/or hip (osteoporosis range), likely severe given 2 fractures

2. Blood tests (to exclude secondary causes and assess baseline):

• Full blood count: Anaemia might suggest myeloma, chronic disease, malabsorption
  • Expected: Normal (primary osteoporosis)
• ESR/CRP: Elevated in myeloma, inflammatory conditions
  • Expected: Normal
• Bone profile (calcium, phosphate, alkaline phosphatase):
  • Primary osteoporosis: All normal
  • Abnormalities suggest secondary causes:
    • High calcium: Hyperparathyroidism, malignancy
    • Low calcium + high ALP: Osteomalacia (vitamin D deficiency)
    • High ALP alone: Paget's disease, recent fracture (healing), metastases
  • Expected in this patient: Normal calcium and phosphate; ALP may be slightly elevated (recent fracture healing)
• 25-hydroxyvitamin D: Check for vitamin D deficiency (very common, especially in elderly, those with low sun exposure)
  • Deficiency: <25 nmol/L; insufficiency: 25-50 nmol/L; replete: >50 nmol/L
  • Expected: Likely low/insufficient (inadequate sun exposure, low dairy intake, PPI use may impair absorption)
• Renal function (U&Es, creatinine, eGFR): Baseline before starting bisphosphonates (contraindicated if eGFR <30-35 ml/min); chronic kidney disease causes secondary osteoporosis
  • Expected: Normal
• Thyroid function (TSH, free T4): Hyperthyroidism causes bone loss
  • Expected: Normal
• Liver function tests: Chronic liver disease causes secondary osteoporosis
  • Expected: Normal

3. Additional tests if secondary causes suspected:

• Parathyroid hormone (PTH): If calcium abnormal (exclude primary hyperparathyroidism)
• Testosterone, LH, FSH: In men <70 with osteoporosis (exclude hypogonadism)
• Coeliac serology (tissue transglutaminase antibodies): If GI symptoms or unexplained osteoporosis in younger patients
• Protein electrophoresis, Bence Jones protein: If suspicion of myeloma (anaemia, high ESR, high calcium, back pain)
• 24-hour urinary calcium: If recurrent renal stones (exclude hypercalciuria)

4. Imaging:

• Spine X-ray (lateral thoracic and lumbar): Identify vertebral fractures (many are asymptomatic)
  • Expected: T12 vertebral crush fracture (known), may identify additional asymptomatic vertebral fractures, thoracic kyphosis
• X-ray of other fracture sites if not already done

Expected investigation results in this patient:

• DEXA scan: T-score ≤ -2.5 (osteoporosis), likely at spine and hip; may show T-score ≤ -3 to -4 (severe) given two fractures
• Blood tests:
  • FBC: Normal
  • Bone profile: Normal calcium and phosphate, possibly mildly elevated ALP (fracture healing)
  • Vitamin D: Low or insufficient (common in elderly, especially with low dairy intake and PPI use)
  • Renal, liver, thyroid function: Normal
• Spine X-ray: T12 crush fracture, possible additional vertebral fractures, thoracic kyphosis

Fracture risk assessment tools:

• FRAX® (Fracture Risk Assessment Tool):
  • WHO-developed calculator estimating 10-year probability of major osteoporotic fracture and hip fracture
  • Uses clinical risk factors +/- BMD
  • Useful for deciding whether to treat patients with osteopenia or without fragility fracture
  • Less relevant for this patient who already has fragility fractures (already meets treatment threshold)
• Q-Fracture: UK-developed tool, similar to FRAX

Key points:

• Fragility fracture = clinical diagnosis of osteoporosis - treatment should be started regardless of BMD
• DEXA scan quantifies severity and provides baseline for monitoring
• Blood tests exclude secondary causes (though most cases are primary)
• Vitamin D deficiency is very common and should be identified and treated

Clinical presentations of osteoporotic fractures:

1. Vertebral fractures (most common osteoporotic fracture):

Presentation:

• Two-thirds are asymptomatic or minimally symptomatic - discovered incidentally on imaging
• Symptomatic fractures:
  • Sudden onset of severe back pain (often mid-thoracic or thoracolumbar region)
  • Often triggered by minimal trauma (bending, lifting, coughing, sneezing) or spontaneous
  • Pain typically sharp, localized to fracture site initially, then becomes more diffuse
  • Worsened by standing, walking, sitting; relieved by lying flat
  • Usually improves over 6-12 weeks but may have chronic pain

Physical signs:

• Point tenderness over affected vertebra
• Height loss: >4cm from peak height is significant; each vertebral fracture causes ~1cm height loss
• Kyphosis ("dowager's hump"): Progressive thoracic curvature from multiple thoracic fractures
• Reduced distance between lower ribs and iliac crest (due to spinal shortening)
• Neurological deficit is rare (distinguish from traumatic fractures, malignancy)

Consequences of vertebral fractures:

• Pain: Acute (4-6 weeks) and chronic back pain
• Disability: Impaired mobility, reduced quality of life
• Deformity: Progressive kyphosis
• Reduced lung capacity: Restrictive lung defect from spinal deformity; can cause dyspnoea, reduced exercise tolerance
• Gastrointestinal symptoms: Early satiety, constipation, abdominal distension (reduced abdominal cavity space)
• Psychosocial impact: Depression, loss of self-esteem, social isolation
• Increased mortality: Particularly multiple vertebral fractures associated with increased mortality (mechanism unclear - marker of frailty)
• Cascade effect: Each vertebral fracture significantly increases risk of further vertebral fractures (altered biomechanics)

2. Hip fracture (femoral neck or intertrochanteric fracture):

Presentation:

• Almost always symptomatic and acute presentation
• Sudden onset severe hip/groin pain following fall (usually from standing height)
• Unable to weight-bear on affected leg
• Requires hospital admission and surgical fixation in majority

Physical signs:

• Affected leg shortened and externally rotated (classic for displaced intracapsular fracture)
• Severe pain on movement of hip
• Bruising around hip (may develop over hours-days)

Consequences (most serious osteoporotic fracture):

• High mortality: ~20-30% mortality at 1 year post-fracture
  • Highest in first 6 months
  • Due to complications, comorbidities, loss of independence
• Loss of independence: ~50% never regain pre-fracture mobility; many require long-term care/nursing home
• Complications: Pneumonia, pressure sores, VTE, delirium, surgical complications
• Chronic pain and disability
• High healthcare costs: Surgery, prolonged hospitalization, rehabilitation, long-term care

3. Distal radius fracture (Colles' fracture):

Presentation:

• Fall onto outstretched hand (FOOSH injury)
• Immediate pain, swelling, deformity at wrist
• Classic "dinner fork" deformity (dorsal displacement and angulation of distal fragment)

Management and consequences:

• Usually managed with closed reduction and cast immobilization (or surgery if unstable)
• Generally good functional recovery
• Significance: Often the first osteoporotic fracture (occurs earlier, typically age 60-70); serves as "warning fracture" - indicates high risk of subsequent hip or vertebral fractures
  • Should prompt osteoporosis assessment and treatment
• Possible long-term complications: Carpal tunnel syndrome, reduced grip strength, arthritis, complex regional pain syndrome

4. Proximal humerus fracture:

Presentation:

• Fall onto shoulder or outstretched arm
• Pain, swelling, bruising around shoulder
• Reduced range of motion

Management and consequences:

• Often managed conservatively with sling, physiotherapy
• Complications: Frozen shoulder, reduced shoulder function

5. Other sites:

• Pelvis fractures: Can occur from minimal trauma; pubic rami fractures common; present with groin/pelvic pain, difficulty mobilizing
• Proximal femur (below hip): Less common
• Ribs: From minor trauma or coughing

General features of osteoporotic (fragility) fractures:

• Occur with minimal or no trauma (fall from standing height or less)
• Occur predominantly in older adults (\>50 years, especially >65 years)
• More common in postmenopausal women
• Recurrent fractures common if untreated (fracture begets fracture)
• May be first presentation of osteoporosis (previously asymptomatic)

Specific complications of vertebral fractures (summary):

Physical complications:

• Acute and chronic pain
• Height loss (progressive with multiple fractures)
• Kyphosis ("dowager's hump" - progressive spinal curvature)
• Restrictive lung disease (reduced FVC from thoracic deformity) → dyspnoea, reduced exercise tolerance
• GI symptoms: early satiety, reflux (increased intra-abdominal pressure), constipation, bloating
• Impaired balance and gait
• Increased risk of falls (due to altered posture and balance)
• Difficulty with activities of daily living (bending, reaching, dressing)

Psychosocial complications:

• Depression and anxiety
• Reduced quality of life
• Loss of self-esteem and body image concerns
• Social isolation (reduced mobility, embarrassment about appearance)
• Fear of falling and further fractures

Cascade effect:

• Each vertebral fracture increases risk of subsequent vertebral fracture by 5-fold
• Also increases risk of hip and other fractures
• Altered spinal biomechanics from one fracture increases load on adjacent vertebrae

Mortality:

• Increased mortality compared to age-matched controls without fractures
• Particularly significant with multiple vertebral fractures
• Mortality less than hip fractures but still clinically significant

Clinical implications:

• Any fragility fracture should prompt comprehensive osteoporosis assessment and treatment
• Vertebral fractures often overlooked (many asymptomatic) - should actively look for them (height loss, kyphosis, spine X-rays)
• Early intervention can prevent subsequent fractures and their devastating consequences
• Hip fracture prevention is a major public health priority due to high morbidity and mortality

General principles of osteoporosis management:

• Goals: Prevent fractures, maintain bone mass, reduce falls risk, manage pain, maintain function
• Multimodal approach: Lifestyle + pharmacological + falls prevention
• Long-term management required (osteoporosis is chronic condition)

1. Lifestyle and non-pharmacological interventions (for all patients):

a) Adequate calcium intake:

• Recommended: 700-1200mg/day (ideally from diet)
• Dietary sources: Dairy products (milk, cheese, yogurt - best sources), green leafy vegetables, fortified foods, sardines/salmon with bones, almonds
• If dietary intake inadequate: Calcium supplementation (e.g., calcium carbonate 500-600mg 1-2 times daily, taken with food for better absorption)
• Important: Calcium alone does NOT prevent fractures; must be combined with vitamin D and/or antiresorptive therapy

b) Vitamin D sufficiency:

• Recommended serum level: >50 nmol/L (some guidelines recommend >75 nmol/L for bone health)
• Sources: Sunlight exposure (15-20 minutes daily on face/arms), fatty fish, egg yolks, fortified foods
• Supplementation: 800-2000 IU (20-50 mcg) daily
  • Higher loading doses if deficient (e.g., 20,000 IU weekly for 8 weeks, then maintenance)
• Essential for calcium absorption and bone mineralization
• Also improves muscle strength and may reduce falls

c) Weight-bearing and resistance exercise:

• Weight-bearing exercise: Walking, jogging, dancing, stair climbing (stimulates bone formation)
• Resistance training: Weights, resistance bands (builds muscle and bone strength)
• Balance and flexibility exercises: Tai chi, yoga (reduce falls risk)
• Recommendation: 30 minutes most days; combination of weight-bearing and resistance exercise
• Benefits: Increases/maintains bone density, improves muscle strength, balance, coordination; reduces falls risk

d) Smoking cessation:

• Smoking toxic to bone cells, reduces estrogen levels, increases fracture risk
• Offer smoking cessation support

e) Moderate alcohol intake:

• Limit to ≤2 units/day (excessive alcohol harmful to bone and increases falls)

f) Maintain healthy body weight:

• Avoid being underweight (BMI <19 increases risk)
• Weight-bearing mechanical load stimulates bone formation

g) Falls prevention:

• Home safety assessment: Remove trip hazards (rugs, clutter), improve lighting, install grab rails (bathroom, stairs), non-slip mats
• Vision assessment and correction: Regular eye tests, update glasses
• Medication review: Minimize sedatives, optimize management of postural hypotension
• Footwear: Well-fitting, non-slip shoes; avoid slippers, high heels
• Hip protectors: Padded undergarments (evidence mixed; may be useful in nursing home residents)
• Balance and strength training: Physiotherapy-led programs

2. Pharmacological treatment:

Indications for pharmacological treatment:

• Fragility fracture (vertebral, hip, distal radius, proximal humerus, pelvis) in patient >50 years
• T-score ≤ -2.5 at spine or hip (without fragility fracture)
• T-score between -1.0 and -2.5 (osteopenia) + high 10-year fracture risk on FRAX
• Long-term glucocorticoid use (≥7.5mg prednisolone ≥3 months) - initiate treatment even with normal BMD

First-line pharmacological treatment - Bisphosphonates:

Mechanism: Inhibit osteoclast-mediated bone resorption; reduce bone turnover; increase or stabilize BMD; reduce fracture risk

Options:

• Oral bisphosphonates (most commonly used):
  • Alendronate (alendronic acid): 70mg once weekly (or 10mg daily)
    • Reduces vertebral fractures by ~50%, hip fractures by ~50%
    • First-line for most patients
  • Risedronate: 35mg once weekly
    • Similar efficacy to alendronate
    • Alternative if alendronate not tolerated
• Intravenous bisphosphonates (if oral not tolerated/contraindicated):
  • Zoledronic acid (zoledronate): 5mg IV infusion once yearly
    • Excellent compliance (once yearly)
    • Bypasses GI side effects
    • Reduces vertebral, hip, and non-vertebral fractures
    • Particularly useful post-hip fracture

Administration instructions (oral bisphosphonates - VERY IMPORTANT):

• Take on empty stomach first thing in the morning
• Swallow whole with full glass (200ml) of plain water
• Remain upright (sitting or standing) for 30 minutes after taking
• Do not eat, drink (except water), or take other medications for 30 minutes
• Rationale: Very poor oral bioavailability; food/other drinks reduce absorption further; remaining upright prevents esophageal irritation

Side effects:

• GI: Dyspepsia, esophageal irritation, nausea (common; improved with proper administration)
• Acute phase reaction (IV): Flu-like symptoms, fever, myalgia (common after first infusion, typically resolves in 1-3 days; advise paracetamol)
• Hypocalcemia (ensure adequate calcium/vitamin D; correct deficiency before starting)
• Atypical femoral fractures (rare, \<1%; associated with long-term use >5 years - prodromal thigh pain)
• Osteonecrosis of jaw (ONJ) - very rare (~0.01%); risk higher with IV bisphosphonates, high doses (cancer treatment), dental procedures, poor dental hygiene
  • Advise dental check before starting, maintain good oral hygiene

Contraindications:

• eGFR <30-35 ml/min (oral), <35 ml/min (IV)
• Hypocalcemia (correct before starting)
• Esophageal abnormalities (stricture, achalasia, inability to stand/sit upright for 30 minutes) - for oral formulations

Duration of treatment:

• Typically 3-5 years initially
• Reassess at 5 years: Consider "drug holiday" (pause treatment for 1-2 years) if low fracture risk and stable BMD
  • Bisphosphonates have long skeletal retention - effects persist after stopping
• Continue beyond 5 years if very high fracture risk (previous fragility fracture, very low BMD)

Second-line/alternative treatments:

Denosumab (Prolia®):

• Mechanism: Monoclonal antibody against RANK ligand; inhibits osteoclast formation and activity
• Dose: 60mg subcutaneous injection every 6 months
• Indications: Alternative to bisphosphonates if not tolerated/contraindicated; can be used in renal impairment (unlike bisphosphonates)
• Efficacy: Reduces vertebral, hip, and non-vertebral fractures
• Side effects: Hypocalcemia (ensure adequate calcium/vitamin D), infections (cellulitis), ONJ (rare), atypical fractures (rare)
• Important: Rebound increased bone turnover and fracture risk if stopped - must transition to bisphosphonate if discontinuing denosumab

Selective Estrogen Receptor Modulators (SERMs) - Raloxifene:

• Mechanism: Estrogen agonist in bone (inhibits resorption), estrogen antagonist in breast
• Dose: 60mg daily
• Indications: Postmenopausal women; particularly if high breast cancer risk (reduces invasive breast cancer risk)
• Efficacy: Reduces vertebral fractures; NO reduction in hip/non-vertebral fractures (less effective than bisphosphonates)
• Side effects: Hot flushes, leg cramps, increased VTE risk
• Contraindications: VTE history, immobility

Anabolic agents (bone-building drugs - specialist use):

• Teriparatide (recombinant PTH 1-34):
  • Mechanism: Stimulates osteoblasts, builds new bone (anabolic)
  • Dose: 20mcg SC daily for maximum 24 months (lifetime limit)
  • Indications: Severe osteoporosis (T-score ≤-3.5 or T-score ≤-2.5 + multiple fractures), failed bisphosphonates, glucocorticoid-induced osteoporosis
  • Most potent treatment for increasing BMD and reducing fractures
  • Expensive; specialist-initiated
• Romosozumab (sclerostin inhibitor): Newer anabolic agent; both stimulates bone formation and reduces resorption; specialist use

Hormone Replacement Therapy (HRT):

• Reduces bone loss and fractures in postmenopausal women
• No longer recommended solely for osteoporosis prevention/treatment due to cardiovascular and breast cancer risks
• May be appropriate in younger postmenopausal women (\<60 years) with menopausal symptoms + osteoporosis

3. Monitoring treatment:

• DEXA scan: Repeat every 2-3 years on treatment
  • Assess response: Stable or increased BMD = good response (reduces fracture risk even without significant BMD increase)
  • Declining BMD despite treatment: Check adherence, investigate secondary causes, consider alternative treatment
• Biochemical markers of bone turnover (CTX, P1NP): Can assess early response but not routinely used
• Calcium and vitamin D levels: Ensure maintained in normal range
• Monitor for side effects, particularly GI symptoms with bisphosphonates

Management plan for this patient (Mrs. Mitchell):

Immediate actions:

• Initiate pharmacological treatment immediately - she has two fragility fractures = clear indication
  • First-line: Alendronate 70mg once weekly (oral bisphosphonate)
    • Provide clear instructions on administration (empty stomach, upright 30 mins, etc.)
    • Alternative: Risedronate 35mg weekly if alendronate not tolerated
    • IV zoledronate once yearly if oral bisphosphonates not tolerated/contraindicated
• Calcium and vitamin D supplementation:
  • Likely vitamin D deficient (check level and replace if low)
  • Start: Calcium 500-600mg + vitamin D 800-2000 IU daily (combined preparation)
  • Counsel on increasing dietary calcium (dairy products)

Investigations:

• Arrange DEXA scan (confirm diagnosis, quantify severity, baseline)
• Blood tests: FBC, bone profile, renal function, LFTs, TFTs, vitamin D, (PTH if calcium abnormal)
• Spine X-ray (identify extent of vertebral fractures)

Lifestyle modifications:

• Increase weight-bearing exercise: Encourage daily walking, consider physiotherapy referral for supervised exercise program
• Improve dietary calcium: Increase dairy intake; consider lactose-free options if lactose intolerance
• Optimize sunlight exposure (sensible, skin cancer risk in mind)

Falls prevention:

• Home safety assessment: Remove rug that caused recent fall, improve lighting, install grab rails if needed
• Vision check (ensure glasses up-to-date)
• Review medications (ensure no sedatives or drugs causing postural hypotension)
• Consider physiotherapy for balance and strengthening exercises

Review PPI:

• Long-term PPI use (5 years) may contribute to reduced calcium absorption
• Review indication - consider step-down/discontinuation trial if appropriate, or lowest effective dose
• If ongoing need, ensure adequate calcium/vitamin D supplementation

Follow-up:

• Review in 3 months: Check adherence, tolerability, address any concerns
• Annual review: Assess for new fractures, symptoms, adherence
• Repeat DEXA scan in 2-3 years to assess treatment response
• Reassess at 5 years for duration of bisphosphonate therapy

Key counseling points:

• Osteoporosis is treatable - treatment can significantly reduce future fracture risk
• Bisphosphonates reduce vertebral fracture risk by ~50%, hip fractures by ~40-50%
• Importance of adherence to medication and proper administration technique
• Treatment is long-term (years), but very effective at preventing devastating hip fractures
• Lifestyle measures (exercise, calcium, vitamin D) are essential adjuncts to medication
• Falls prevention crucial - hip fracture prevention saves lives and independence

Glucocorticoid-induced osteoporosis (GIOP):

Overview:

• Most common cause of secondary osteoporosis
• Occurs in patients taking systemic glucocorticoids (oral, IV, IM) - prednisolone, dexamethasone, hydrocortisone
• Dose-dependent: Risk increases with dose and duration
• Threshold for concern: ≥7.5mg prednisolone (or equivalent) daily for ≥3 months
  • However, bone loss can occur at lower doses and shorter durations
• Very common: Up to 50% of patients on long-term glucocorticoids develop fractures

Pathophysiology - how glucocorticoids damage bone:

Direct effects on bone cells:

• Decreased bone formation: Inhibit osteoblast function and lifespan; reduce osteoblast differentiation from precursors
• Increased bone resorption: Increase osteoclast activity and lifespan (via RANKL pathway)
• Induce osteocyte apoptosis (death of mature bone cells embedded in bone matrix)
• Net result: Rapid bone loss, particularly trabecular bone (spine affected early)

Indirect effects:

• Reduced calcium absorption: Inhibit intestinal calcium absorption
• Increased renal calcium excretion: Causes hypercalciuria
• Secondary hyperparathyroidism: Low calcium → increased PTH → increased bone resorption
• Hypogonadism: Reduce sex hormone production (testosterone, estrogen)
• Myopathy and reduced muscle mass: Muscle weakness → reduced mechanical loading on bone, increased falls risk

Time course of bone loss:

• Rapid bone loss in first 3-6 months (most rapid initially, up to 12% per year)
• Bone loss continues (though slower) with ongoing treatment
• Partially reversible if glucocorticoids stopped, but fracture risk remains elevated

Fracture risk in GIOP:

• Fracture risk INCREASED at any given BMD compared to primary osteoporosis
  • Bone quality (architecture, collagen structure) is impaired, not just quantity (BMD)
  • Fractures can occur even with "normal" or "osteopenic" BMD
• Vertebral fractures most common (trabecular bone affected earliest and most severely)
• Also increased risk of hip, rib, and other fractures
• Dose-response: Higher doses and longer duration → higher fracture risk

Risk assessment in GIOP:

Identify patients at high risk:

• Age >65 years
• Previous fragility fracture
• High glucocorticoid dose (≥7.5mg prednisolone daily or equivalent)
• Prolonged duration of use
• Low BMD (T-score ≤-1.5)
• Postmenopausal women or men >50 years
• Additional risk factors (low BMI, family history, smoking, alcohol)
• Falls risk

FRAX tool in GIOP:

• Can be used but may underestimate fracture risk in GIOP
• Adjust threshold for intervention (lower threshold in glucocorticoid users)

Prevention and management of GIOP - key differences from primary osteoporosis:

1. Lower threshold for intervention:

• Initiate bone protection in ALL patients starting glucocorticoids ≥7.5mg prednisolone daily for ≥3 months
• Consider treatment at lower BMD thresholds (e.g., T-score ≤-1.5 rather than ≤-2.5)
• In some cases, treat even with normal BMD if high fracture risk (age >65, previous fracture, high dose steroids)

2. Proactive approach - start bone protection EARLY:

• Don't wait for fracture or DEXA scan before starting treatment
• Bone loss is most rapid in first 3-6 months - early intervention crucial
• NICE guidelines (UK): Offer bone protection to adults starting/taking oral glucocorticoids ≥7.5mg daily for ≥3 months if:
  • Age ≥70 years (any dose, any duration), OR
  • Previous fragility fracture, OR
  • FRAX 10-year major osteoporotic fracture probability ≥10% (calculate using glucocorticoid option)
• Other patients: Arrange DEXA scan and treat based on T-score (≤-1.5)

3. Pharmacological treatment - bisphosphonates are first-line:

• Oral bisphosphonates:
  • Alendronate 70mg once weekly (first-line)
  • Risedronate 35mg once weekly (alternative)
• IV bisphosphonates:
  • Zoledronate 5mg IV once yearly (if oral not tolerated)
• Evidence: Bisphosphonates reduce vertebral fracture risk in GIOP by ~30-70%; prevent bone loss
• Alternative agents:
  • Teriparatide (anabolic agent): May be superior to bisphosphonates in severe GIOP; particularly effective as stimulates bone formation (which is particularly impaired by steroids); specialist use
  • Denosumab: Alternative if bisphosphonates contraindicated/not tolerated

4. Calcium and vitamin D - ESSENTIAL:

• ALL patients on long-term glucocorticoids should receive calcium and vitamin D supplementation
• Glucocorticoids reduce calcium absorption and increase excretion → negative calcium balance
• Dose:
  • Calcium: 1000-1200mg daily (diet + supplement to reach target)
  • Vitamin D: 800-2000 IU (20-50 mcg) daily
• Usually given as combined calcium + vitamin D preparation
• Start at same time as glucocorticoids

5. Minimize glucocorticoid dose and duration:

• Use lowest effective dose for shortest duration
• Consider steroid-sparing agents (e.g., methotrexate, azathioprine in inflammatory conditions) to reduce glucocorticoid requirement
• Consider alternate-day dosing if appropriate for condition
• Avoid abrupt withdrawal (adrenal suppression risk) - gradual taper
• Topical, inhaled, intra-articular glucocorticoids have much lower systemic effects (but high-dose inhaled steroids can still cause bone loss)

6. Lifestyle measures (same as primary osteoporosis):

• Weight-bearing exercise (also counteracts glucocorticoid-induced myopathy)
• Smoking cessation
• Moderate alcohol
• Falls prevention (particularly important as glucocorticoids cause myopathy, increasing falls risk)

7. Monitoring:

• Baseline DEXA scan when starting long-term glucocorticoids (if not already on treatment based on other criteria)
• Repeat DEXA every 1-3 years depending on risk
• Monitor for vertebral fractures (height measurement, symptoms, consider spine X-rays)

8. Duration of treatment:

• Continue bone protection for duration of glucocorticoid treatment
• If glucocorticoids stopped: Continue bone protection for at least 12 months (bone loss partially reversible but fracture risk remains elevated)
• Reassess fracture risk after stopping glucocorticoids (some may need ongoing treatment if other risk factors present)

Summary - key differences GIOP vs. primary osteoporosis:

Aspect	Primary Osteoporosis	Glucocorticoid-Induced Osteoporosis
Onset	Gradual, over years-decades	Rapid, within 3-6 months of starting steroids
Bone most affected	Trabecular and cortical (postmenopausal); cortical > trabecular (senile)	Trabecular bone predominantly (spine affected early)
Fracture risk at given BMD	Correlates with T-score	Higher than predicted by T-score (impaired bone quality)
Treatment threshold (T-score)	≤-2.5 (or fragility fracture)	≤-1.5, or even normal BMD if age >65/previous fracture
Timing of intervention	After diagnosis (DEXA or fracture)	Proactive - start with/soon after initiating steroids
Calcium + vitamin D	Recommended adjunct	ESSENTIAL for all patients (steroids cause calcium wasting)
Reversibility	Not reversible (chronic condition)	Partially reversible if steroids stopped; but treatment still needed
Prevention focus	Lifestyle + treat established disease	Prevention crucial - minimize dose/duration, start bone protection early

Clinical scenario - patient starting prednisolone:

Example: 60-year-old woman starting prednisolone 15mg daily for polymyalgia rheumatica

Approach:

• Assess fracture risk: Age, BMI, previous fractures, family history, other risk factors
• Start calcium + vitamin D immediately (e.g., Adcal-D3 or equivalent)
• Initiate bisphosphonate if:
  • Age ≥70, OR
  • Previous fragility fracture, OR
  • High fracture risk on FRAX (≥10% major osteoporotic fracture)
• If doesn't meet above criteria: Arrange baseline DEXA scan
  • If T-score ≤-1.5: Start bisphosphonate
  • If T-score >-1.5: Continue calcium/vitamin D, repeat DEXA in 1-2 years, monitor
• Lifestyle advice: Weight-bearing exercise, falls prevention
• Optimize steroid regimen: Use minimum effective dose; consider steroid-sparing agents; taper as soon as possible

Key messages:

• GIOP is common, serious, but preventable with proactive management
• Start bone protection early - don't wait for fracture
• All patients on long-term steroids need calcium + vitamin D as minimum
• Bisphosphonates are effective and should be offered to high-risk patients
• Minimize glucocorticoid dose and duration whenever possible
• Fracture risk is higher at any given BMD in GIOP compared to primary osteoporosis