MANAGEMENT OF OSTEOPOROSISMANAGEMENT OF OSTEOPOROSIS

Professor Opinder SahotaProfessor Opinder Sahota

Consultant Physician Consultant Physician QMC, NottinghamQMC, Nottingham

Financial TurmoilFinancial 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% by2020

For a typical 300K PCT :

OSTEOPOROSISOSTEOPOROSIS

DefinitionDefinition

‘‘Systemic skeletal disease Systemic skeletal disease

characterised by low bone masscharacterised by low bone mass

and microarchitectural and microarchitectural

deterioration in bone tissue, deterioration in bone tissue,

with consequent with consequent

increase in bone fragility andincrease in bone fragility and

susceptibility to fracture’susceptibility to fracture’

Common Sites of FractureCommon Sites of Fracture

VERTEBRAL FRACTURESVERTEBRAL FRACTURES

WHAT IS A VERTEBRAL FRACTURE ?WHAT IS A VERTEBRAL FRACTURE ?

RISK FACTORS FOR OSTEOPOROSISRISK FACTORS FOR OSTEOPOROSIS

SECONDARY CAUSESSECONDARY CAUSES

• METABOLIC CONDITIONSMETABOLIC CONDITIONS PRIMARY HYPERPARATHYROIDISM PRIMARY HYPERPARATHYROIDISM OSTEOMALACIA OSTEOMALACIA THYROTOXICOSIS THYROTOXICOSIS OSTEOGENESIS IMPERFECTA OSTEOGENESIS IMPERFECTA

• OTHER DISEASESOTHER DISEASES HYPOGONADISM (MALE / FEMALE) HYPOGONADISM (MALE / FEMALE) MALABSORPTION MALABSORPTION MALNUTRITION MALNUTRITION ANOREXIA NERVOSA ANOREXIA NERVOSA MALIGNANCY MALIGNANCY

RISK FACTORS FOR OSTEOPOROSISRISK FACTORS FOR OSTEOPOROSIS

• PREVIOUS LOW TRAUMA FRACTUREPREVIOUS LOW TRAUMA FRACTURE

• CORTICOSTEROIDSCORTICOSTEROIDS (ANTICIPATED / ACCUMULATIVE (ANTICIPATED / ACCUMULATIVE 3 months) 3 months)

CORTICOSTERIODSCORTICOSTERIODS

• AGE > 65 YRS AGE > 65 YRS

TREATTREAT -LOW TRAUMA FRACTURE-LOW TRAUMA FRACTURE 1mg or more for 3 mths or more / 2 bolus int dose 1mg or more for 3 mths or more / 2 bolus int dose

-NO FRACTURE -NO FRACTURE >5mg daily / 3 int doses per year >5mg daily / 3 int doses per year

• AGE < 65 YRS AGE < 65 YRS

DXADXA

CONSIDER IF NOT DONE WITHIN THE LAST 6 MTHSCONSIDER IF NOT DONE WITHIN THE LAST 6 MTHS

• AP/LAT SPINAL X-RAYS AP/LAT SPINAL X-RAYS

• FBC, ESRFBC, ESR

• BIOCHEMISTRY PROFILE (CALCIUM)BIOCHEMISTRY PROFILE (CALCIUM)

• TFT / PTHTFT / PTH

• PROTEIN ELECTROPHORESISPROTEIN ELECTROPHORESIS URINE BENCE JONES PROTEIN URINE BENCE JONES PROTEIN

• TESTOSTERONETESTOSTERONE

• OESTRADIOL OESTRADIOL (PREMENOPAUSAL AMENORRHOEIC WOMEN) (PREMENOPAUSAL AMENORRHOEIC WOMEN)

DIAGNOSTIC WORK UP

THERAPEUTIC THERAPEUTIC OPTIONSOPTIONS

THERAPEUTIC OPTIONS THERAPEUTIC OPTIONS

ANALGESIAANALGESIA• PARACETAMOLPARACETAMOL

• TRAMADOLTRAMADOL

• NSAIDS / COXIBNSAIDS / COXIB

SURGICAL OPTIONS SURGICAL OPTIONS

VERTEBROPLASTY / KYPHOPLASTYVERTEBROPLASTY / KYPHOPLASTY

• STOP SMOKING

• ALCOHOL WITHIN LIMITATION

• OPTIMAL ANALGESIA

• CALCIUM & VITAMIN D [CALCICHEW D3 FORTE 1 TAB BD]

MANAGEMENT OF OSTEOPOROSISMANAGEMENT OF OSTEOPOROSIS

NICE Health Technology Appraisal 160,161 Oct 08

REDUCING VERTEBRAL & HIP FRACTURE RISKREDUCING VERTEBRAL & HIP FRACTURE RISK

Which Bisphosphonate ?

HTA NICE OsteoporosisHTA NICE Osteoporosis

• WeeklyAlendronate

(generic-cheap, but poor formulation)

Ibandronate

Risedronate

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 10 11 12

Daily alendronate Weekly alendronate

DIN-LINK data: continuous adherence to DIN-LINK data: continuous adherence to medication for patients receiving daily or weekly medication for patients receiving daily or weekly alendronatealendronate

Months of treatment

Per

cent

age

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 OsteoporosisHTA NICE Osteoporosis

Zoledronate iv

HTA NICE OsteoporosisHTA NICE Osteoporosis

Osteonecrosis of the Jaw

HTA NICE OsteoporosisHTA 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 PrefusionOsteoclast

MultinucleatedOsteoclast

HormonesGrowth FactorsCytokines

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-GMPrefusionOsteoclast

Osteoblasts

RANKL

RANK

OPG

HormonesGrowth FactorsCytokines

Excess RANK Ligand Can Increase Bone Resorption Leading to Osteoporosis

Bone Formation

Bone Resorption

Activated Osteoclast

CFU-GM PrefusionOsteoclast

MultinucleatedOsteoclast

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 PrefusionOsteoclast

Osteoblasts

HormonesGrowth FactorsCytokines

FRACTURE PATHOGENESISFRACTURE PATHOGENESIS

FORCE

FRAGILITY

FALL

Falls : MedicationFalls : Medication