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MANAGEMENT OF OSTEOPOROSIS Professor Opinder Sahota Consultant Physician QMC, Nottingham. Financial Turmoil. £15 billion cost saving over the next 3 yrs £1.5 billion for the SHA £300 million for each health community 1 ward closure = £1 MILLION.
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MANAGEMENT OF OSTEOPOROSIS Professor Opinder SahotaConsultant Physician QMC, Nottingham
Financial Turmoil • £15 billion cost saving over the next 3 yrs • £1.5 billion for the SHA • £300 million for each health community • 1 ward closure = £1 MILLION
> 15,000 will fall each year, >6000 twice or more Most will not call for help >70/week will attend A&E or the MIU A similar number will call the ambulance service 350 hip fractures/year ~1000 other fragility fractures Average PCT & council costs on falls are £50m per annum Ageing demography means this will increase 50% by 2020 For a typical 300K PCT :
Common Sites of Fracture OSTEOPOROSIS Definition ‘Systemic skeletal disease characterised by low bone mass and microarchitectural deterioration in bone tissue, with consequent increase in bone fragility and susceptibility to fracture’
VERTEBRAL FRACTURES WHAT IS A VERTEBRAL FRACTURE ?
RISK FACTORS FOR OSTEOPOROSIS • SECONDARY CAUSES • METABOLIC CONDITIONSPRIMARY HYPERPARATHYROIDISM OSTEOMALACIA THYROTOXICOSIS OSTEOGENESIS IMPERFECTA • OTHER DISEASESHYPOGONADISM (MALE / FEMALE) MALABSORPTION MALNUTRITION ANOREXIA NERVOSA MALIGNANCY
RISK FACTORS FOR OSTEOPOROSIS • PREVIOUS LOW TRAUMA FRACTURE • CORTICOSTEROIDS (ANTICIPATED / ACCUMULATIVE 3 months)
CORTICOSTERIODS • AGE > 65 YRS • TREAT-LOW TRAUMA FRACTURE 1mg or more for 3 mths or more / 2 bolus int dose • -NO FRACTURE >5mg daily / 3 int doses per year • AGE < 65 YRS • DXA
DIAGNOSTIC WORK UP CONSIDER IF NOT DONE WITHIN THE LAST 6 MTHS • AP/LAT SPINAL X-RAYS • FBC, ESR • BIOCHEMISTRY PROFILE (CALCIUM) • TFT / PTH • PROTEIN ELECTROPHORESIS URINE BENCE JONES PROTEIN • TESTOSTERONE • OESTRADIOL (PREMENOPAUSAL AMENORRHOEIC WOMEN)
THERAPEUTIC OPTIONS • ANALGESIA • PARACETAMOL • TRAMADOL • NSAIDS / COXIB
SURGICAL OPTIONS VERTEBROPLASTY / KYPHOPLASTY
MANAGEMENT OF OSTEOPOROSIS • STOP SMOKING • ALCOHOL WITHIN LIMITATION • OPTIMAL ANALGESIA • CALCIUM & VITAMIN D[CALCICHEW D3 FORTE 1 TAB BD]
REDUCING VERTEBRAL & HIP FRACTURE RISK NICE Health Technology Appraisal 160,161 Oct 08
WeeklyAlendronate • (generic-cheap, but poor formulation) HTA NICE Osteoporosis Which Bisphosphonate ? Ibandronate Risedronate
DIN-LINK data: continuous adherence to medication for patients receiving daily or weekly alendronate Percentage Months of treatment DIN-LINK data CompuFile Ltd., May ’05 "adherence was measured over one year as the length of continuous therapy, with cessation being defined as an interval in excess of 1.5 times the expected prescription duration".
HTA NICE Osteoporosis Which Bisphosphonate ? Zoledronate iv
HTA NICE Osteoporosis • Osteonecrosis of the Jaw
HTA NICE Osteoporosis • Osteonecrosis of the Jaw • Many associated with dental procedures(tooth extraction) • Many have signs of local infection including osteomyelitis • Advice MHRA • Dental exam with approp dentistry in patients with risk factors(cancer, chemo, corticosteroids, poor oral hygiene) • While on treatment, avoid invasive dental procedures
RANK ligand member of the TNF superfamily Denosumab is a fully human monoclonal antibody to RANK ligand High affinity and specificity for human RANK ligand No detectable binding to other members of the TNF family: TNF-α, TNF-β, TRAIL, or CD40 ligand No neutralizing antibodies detected in trials Denosumab (Prolia)
RANK Ligand Is an Essential Mediator of Osteoclast Formation, Function, and Survival RANKL RANK PrefusionOsteoclast CFU-GM MultinucleatedOsteoclast HormonesGrowth Factors Cytokines Activated Osteoclast Osteoblasts Bone Formation Bone Resorption
OPG Is a Decoy Receptor That Prevents RANK Ligand Binding to RANK and Inhibits Osteoclast Formation, Function, and Survival CFU-GM PrefusionOsteoclast RANKL RANK OPG HormonesGrowth Factors Cytokines Osteoclast Formation, Function, and Survival Inhibited Osteoblasts Bone Resorption Inhibited Bone Formation
Excess RANK Ligand Can Increase Bone Resorption Leading to Osteoporosis RANKL RANK OPG PrefusionOsteoclast CFU-GM MultinucleatedOsteoclast Decreased Estrogen Leads to Increased RANK Ligand Activated Osteoclast Osteoblasts Bone Formation Bone Resorption
Denosumab Binds RANK Ligand and Inhibits Osteoclast Formation, Function, and Survival RANKL RANK OPGDenosumab PrefusionOsteoclast CFU-GM HormonesGrowth Factors Cytokines Osteoclast Formation, Function, and Survival Inhibited Osteoblasts Bone Resorption Inhibited Bone Formation
FRACTURE PATHOGENESIS FRAGILITY FORCE FALL