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

> 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 :

OSTEOPOROSISDefinition ‘Systemic skeletal disease characterised by low bone mass and microarchitectural deterioration in bone tissue, with consequent increase in bone fragility and susceptibility to fracture’ Common Sites of Fracture

VERTEBRAL FRACTURES WHAT IS A VERTEBRAL FRACTURE ?

RISK FACTORS FOR OSTEOPOROSIS SECONDARY CAUSES METABOLIC CONDITIONS PRIMARY HYPERPARATHYROIDISM OSTEOMALACIA THYROTOXICOSIS OSTEOGENESIS IMPERFECTA METABOLIC CONDITIONS PRIMARY HYPERPARATHYROIDISM OSTEOMALACIA THYROTOXICOSIS OSTEOGENESIS IMPERFECTA OTHER DISEASES HYPOGONADISM (MALE / FEMALE) MALABSORPTION MALNUTRITION ANOREXIA NERVOSA MALIGNANCY OTHER DISEASES HYPOGONADISM (MALE / FEMALE) MALABSORPTION MALNUTRITION ANOREXIA NERVOSA MALIGNANCY

RISK FACTORS FOR OSTEOPOROSIS PREVIOUS LOW TRAUMA FRACTURE PREVIOUS LOW TRAUMA FRACTURE CORTICOSTEROIDS (ANTICIPATED / ACCUMULATIVE  3 months) CORTICOSTEROIDS (ANTICIPATED / ACCUMULATIVE  3 months)

CORTICOSTERIODS AGE > 65 YRS AGE > 65 YRS TREAT -LOW TRAUMA FRACTURE 1mg or more for 3 mths or more / 2 bolus int dose 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 -NO FRACTURE >5mg daily / 3 int doses per year AGE < 65 YRS AGE < 65 YRS DXA DXA

CONSIDER IF NOT DONE WITHIN THE LAST 6 MTHS AP/LAT SPINAL X-RAYS AP/LAT SPINAL X-RAYS FBC, ESR FBC, ESR BIOCHEMISTRY PROFILE (CALCIUM) BIOCHEMISTRY PROFILE (CALCIUM) TFT / PTH TFT / PTH PROTEIN ELECTROPHORESIS URINE BENCE JONES PROTEIN PROTEIN ELECTROPHORESIS URINE BENCE JONES PROTEIN TESTOSTERONE TESTOSTERONE OESTRADIOL (PREMENOPAUSAL AMENORRHOEIC WOMEN) OESTRADIOL (PREMENOPAUSAL AMENORRHOEIC WOMEN) DIAGNOSTIC WORK UP

THERAPEUTIC OPTIONS

THERAPEUTIC OPTIONS THERAPEUTIC OPTIONS ANALGESIA ANALGESIA PARACETAMOLPARACETAMOL TRAMADOLTRAMADOL NSAIDS / COXIBNSAIDS / COXIB

SURGICAL OPTIONS SURGICAL OPTIONS VERTEBROPLASTY / KYPHOPLASTY

STOP SMOKING ALCOHOL WITHIN LIMITATION OPTIMAL ANALGESIA CALCIUM & VITAMIN D [CALCICHEW D3 FORTE 1 TAB BD] MANAGEMENT OF OSTEOPOROSIS

NICE Health Technology Appraisal 160,161 Oct 08 REDUCING VERTEBRAL & HIP FRACTURE RISK

Which Bisphosphonate ? HTA NICE Osteoporosis Weekly Alendronate (generic-cheap, but poor formulation) Ibandronate Risedronate

DIN-LINK data: continuous adherence to medication for patients receiving daily or weekly alendronate Months of treatment Percentage 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".

Which Bisphosphonate ? HTA NICE Osteoporosis 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

PTH (Teriparatide) PTH (Teriparatide)

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) Denosumab (Prolia)

RANK Ligand Is an Essential Mediator of Osteoclast Formation, Function, and Survival Osteoblasts Activated Osteoclast CFU-GM Prefusion Osteoclast Multinucleated Osteoclast Hormones Growth Factors Cytokines Bone Formation Bone Resorption RANKL RANK

OPG Is a Decoy Receptor That Prevents RANK Ligand Binding to RANK and Inhibits Osteoclast Formation, Function, and Survival Bone Formation Bone Resorption Inhibited Osteoclast Formation, Function, and Survival Inhibited CFU-GM Prefusion Osteoclast Osteoblasts RANKL RANK OPG Hormones Growth Factors Cytokines

Excess RANK Ligand Can Increase Bone Resorption Leading to Osteoporosis Bone Formation Bone Resorption Activated Osteoclast CFU-GM Prefusion Osteoclast Multinucleated Osteoclast Osteoblasts RANKL RANK OPG Decreased Estrogen Leads to Increased RANK Ligand

Denosumab Binds RANK Ligand and Inhibits Osteoclast Formation, Function, and Survival RANKL RANK OPG Denosumab Bone Formation Bone Resorption Inhibited Osteoclast Formation, Function, and Survival Inhibited CFU-GM Prefusion Osteoclast Osteoblasts Hormones Growth Factors Cytokines

FRACTURE PATHOGENESIS FORCE FRAGILITY FALL

Falls : Medication