Overview Osteoporosis and Metabolic Bone Disease Dr Chandini Rao Consultant Rheumatologist Bone Biology Osteoporosis Osteomalacia Paget s Disease Cases Bone Biology Osteoporosis Increased bone remodelling Structural deterioration Increased skeletal fragility Increased fracture risk 1
Definition of Osteoporosis A disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility in fracture risk 1 Osteoporosis: T score < -2.5 Osteopenia: T score between -1.0 and -2.5 NB. T scores compare BMD to the average individual at peak bone mass Z scores are age matched Scanning electron microscopy of normal and osteoporotic bone Normal Osteoporotic Life-time prevalence of fragility fracture* in the over-50s 1 Consensus Development Conference. Am J Med 1991;90:107 10 Dempster DW, et al. J Bone Miner Res 1986;1:15 21 * From standing height or less Epidemiology of Fragility Fractures Mortality and morbidity 12 months after hip fracture The Domino Fracture Effect For women > 50: 1 in 3 Vertebral # 1 in 5 Hip # Dead Unable to walk unaided 20 40 If prior vertebral #: RR of further vertebral # = 4.4 RR of hip # = 2.3 RR of wrist # = 1.4 NICE TA 160, 161 Oct 2008 Difficulty with > 1 60 essential activity Restricted in other 80 activities 0 20 40 60 80 100 % 12 months after fracture Am J Med 1997 Osteoporosis Int 2000 15 Fragility Fractures in the UK 180,000 fragility fractures in England/Wales per yr: 70,000 hip # 25,000 vertebral # 41,000 wrist # Combined cost of hospital and social care for hip # = 2.3 billion/yr Assessing Fracture Risk Risk factors for osteoporosis Risk factors for falls Bone mineral density DEXA scan NICE TA 160, 161 Oct 2008 2
Fracture risk tool (FRAX) To estimate the 10yr absolute fracture risk for all osteoporotic fractures and hip fracture the FRAX tool can be accessed at www.shef.ac.uk/frax FRAX has only been validated for patients who are treatment naïve and not for those who have been receiving treatment for osteoporosis Use with caution in patients whose spine BMD is lower than their hip BMD Can be used with or without BMD FRAX risk factors Age Sex Weight Height Previous fracture Parent hip fracture Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol 3 units or more / day Osteoporosis management algorithm for postmenopausal women and men > 50 years old Age 75 Low trauma # Age <75 Low trauma # No # Clinical risk factor Assess for underlying causes Lifestyle advice Treat Measure BMD by DEXA Osteoporosis No Osteoporosis (T score <-2.5) (T score > -2.5) Estimate fracture risk using FRAX 3 & 12 month assessment? therapy compliance High risk (NOGG) Low risk (NOGG) Reassure Lifestyle advice These guidelines should not replace clinical judgement Modes of Action of Drugs for Osteoporosis Anti-resorptive (reduce osteoclastic activity) Bisphosphonates (HRT) (Calcitonin) (Raloxifene) Denosumab Anabolic PTH Dual Strontium ranelate (avoid in patients at risk of CVD, VTE) Bisphosphonate Bisphosphonates: Mechanism of action Active osteoclast Inactive osteoclast Apoptotic osteoclast Bisphosphonate taken up by osteoclasts Bone Osteoclasts lose resorptive function upon bisphosphonate uptake Adapted from Rodan GA & Fleish HA. J Clin Invest 1996;12:2692-6 Osteoclastic apoptosis Suggested Treatment Ladder Alendronic acid Risedronate (better GI tolerability) Strontium (if no CV risk factors) Denosumab/IV Zoledronic acid PTH Ensure adequate calcium and vitamin D intake with all treatments Ensure lifestyle factors are addressed Reassess need for therapy after 5 years 3
Case 1 77 yr old female Hypertensive on Bendroflumethiazide # proximal humerus - What questions would you ask? - What (if any) investigations would you request? - What (if any) treatment would you offer? Case 2 73 yr old man Acute on chronic dorsal back pain. Kyphotic. T spine X-ray shows multiple vertebral collapses - What questions would you ask? - What (if any) investigations would you request? - What (if any) treatment would you offer? Case 3 65 year old female Severe RA 35 years Long-term oral steroids (lowest 10mg/day) Recurrent fractures Intolerant of oral bisphosphonates DEXA T score: Lspine - 3.4 Hip - 3.7 On IV bisphosphonate 3 years BMD unchanged but continues to fracture - How would you manage her? Osteomalacia Osteomalacia Decreased mineralisation of newly formed osteoid at sites of bone turnover in adults (NB. Rickets defect of mineralisation in the growing skeleton) Commonest cause in UK Vitamin D deficiency Clinical Features of Osteomalacia May be asymptomatic Bone pain Proximal myopathy Fracture (ribs, vertebrae, long bones, pelvis) Mobility problems ( waddling gait ) Muscle spasms/cramps Tingling/numbness Positive Chvostek s sign, tetany etc 4
Laboratory findings 25(OH) vitamin D < 25nmol/l (10μg/l) Elevated alkaline phosphatase Low serum calcium and phosphate Elevated PTH If investigations equivocal,? Bone biopsy Treatment of Osteomalacia Vitamin D replacement! Standard doses of calcium/vitamin D may be inadequate Colecalciferol 40,000 units/wk for 8 weeks or Fultium D3 3200 units daily for 8-12 weeks then maintenance of 800-1600 units daily Paget s Disease Paget s Disease Accelerated bone remodelling overgrowth of bone at selected sites and impaired integrity Prevalence 3% (autopsy) Male = Female Aetiology: genetic/viral incidence in Anglo-Saxons Clinical Features of Paget s Mostly asymptomatic Pain worse on weightbearing, at night Skeletal deformities Sites: pelvis, skull, long bones, spine, clavicles Fractures Tumours (0.7-1%) Neurological complications Cardiac failure 5
Investigations Normal calcium, phosphate and PTH Alkaline phosphatase urinary hydroxyproline urinary pyridinoline cross-links serum P1NP / CTX, urinary NTX Radiology: plain X-ray, isotope bone scan Treatment of Paget s Indications for therapy: Pain The metabolic activity of pagetic lesions, as determined by bone turnover markers or bone scintigraphy The potential consequences of bony overgrowth at affected sites Planned orthopaedic intervention Treatment: Bisphosphonates - oral Tiludronate/Risedronate - IV Pamidronate or Zoledronic acid Case 4 88yr old male referred with pain in left hip/thigh Reduced mobility Nocturnal pain PMH ca prostate (orchidectomy 2003) O/E L hip ROM 50% ALP 952, egfr 39 X-Ray 6
Progress Received one dose IV Zoledronic acid (with calcium supplementation) Some improvement in pain but not mobility 3 months later, ALP 1361, egfr 23 What s going on? What further investigations are needed? 7