LIFE TIME RISK OF A FRAGILITY FRACTURE

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MANAGEMENT OF OSTEOPOROSIS Professor Opinder
SahotaConsultant Physician QMC, Nottingham
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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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For a typical 300K PCT

• gt 15,000 will fall each year, gt6000 twice or
  more
• Most will not call for help
• gt70/week will attend AE 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

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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
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VERTEBRAL FRACTURES
WHAT IS A VERTEBRAL FRACTURE ?
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RISK FACTORS FOR OSTEOPOROSIS SECONDARY CAUSES

• METABOLIC CONDITIONS PRIMARY
  HYPERPARATHYROIDISM OSTEOMALACIA
  THYROTOXICOSIS OSTEOGENESIS IMPERFECTA
• OTHER DISEASES HYPOGONADISM (MALE / FEMALE)
  MALABSORPTION MALNUTRITION
  ANOREXIA NERVOSA MALIGNANCY

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RISK FACTORS FOR OSTEOPOROSIS

• PREVIOUS LOW TRAUMA FRACTURE
• CORTICOSTEROIDS (ANTICIPATED / ACCUMULATIVE
  ? 3 months)

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CORTICOSTERIODS

• AGE gt 65 YRS
• TREAT -LOW TRAUMA FRACTURE 1mg or more
  for 3 mths or more / 2 bolus int dose
• -NO FRACTURE gt5mg daily / 3 int doses
  per year

• AGE lt 65 YRS
• DXA

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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)

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THERAPEUTIC OPTIONS
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• THERAPEUTIC OPTIONS
• ANALGESIA
• PARACETAMOL
• TRAMADOL
• NSAIDS / COXIB

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SURGICAL OPTIONS VERTEBROPLASTY /
KYPHOPLASTY
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• STOP SMOKING
• ALCOHOL WITHIN LIMITATION
• OPTIMAL ANALGESIA
• CALCIUM VITAMIN D CALCICHEW D3 FORTE 1 TAB
  BD

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REDUCING VERTEBRAL HIP FRACTURE RISK
NICE Health Technology Appraisal 160,161 Oct 08
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Which Bisphosphonate ?
HTA NICE Osteoporosis

• Ibandronate
• Risedronate

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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".
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Which Bisphosphonate ?
HTA NICE Osteoporosis
Zoledronate iv
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HTA NICE Osteoporosis

• Osteonecrosis of the Jaw

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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

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PTH (Teriparatide)
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Denosumab (Prolia)

• 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-a, TNF-ß, TRAIL, or CD40 ligand
• No neutralizing antibodies detected in trials

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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
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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
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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
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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
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FRACTURE PATHOGENESIS
FRAGILITY
FORCE
FALL
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Falls Medication