Start treatment for Osteoporosis after Fracture . . . . Teriparatide

( ? )

Start treatment for Osteoporosis after Fracture . . . . Teriparatide

( ? )

Sushrut Hosp, Research Centre & Post-Graduate

Institute of Orthopedics, Nagpur, India.

www . sushrut . org

sushrutdsurgeon@gmail.com

Is treating Osteoporosis a fashion ?

Is treating Osteoporosis a fashion ?

What is the most fashionable drug of choice ?What is the most fashionable drug of choice ?

By the way whats the real Science ? By the way whats the real Science ?

Questions that arise in mind….

Lets listen to this guy what he has to say…..Lets listen to this guy what he has to say…..

Sushrut BabhulkarMS Orth, MCh Liverpool England

4

Projected number of osteoporotic hip fractures worldwide

Projected to reach 3.250 million in Asia by 2050

Adapted from Cooper C et al, Osteoporosis Int, 1992;2:285-289

Estimated no of hip fractures: (1000s)

1950 2050

60

0

32

50

1950 2050

66

8

40

0

1950 2050

74

2

37

8

1950 2050

100

62

9Total number ofhip fractures:1950 = 1.66

million 2050 = 6.26

million

All fractures are associated with morbidity ! ! !

5Cooper C, Am J Med, 1997;103(2A):12S-17S

40%

Unable to walk

independently

30%

Permanentdisability

20%

Death within one year

80%

One year after

an hip fracture:

Pati

en

ts (

%)

Unable to carry out at least one independent activity of daily living

6

Survival after hip fracture

Trombetti A et al, Osteoporos Int, 2002;13:731-737

Hip fractured Women

Hip fractured Men

Women

Men

Expected survival in the general population

2 4 6 8 100.00

0.25

0.50

0.75

1.00

Su

rviv

al p

rob

ab

ilit

y

Time after hip fracture (years)0

FractureBoneStrength

MaterialProperties

Remodeling

FallsShape & Architecture

Exercise & Lifestyle

Hormones

NutritionBone Mass

PosturalReflexes

Soft TissuePadding

Reproduced with permission from Heaney RP. Bone 33:457-465, 2003

Factors Leading to Osteoporotic Fracture: Role of Bone Remodeling

2004

8

Pathogenesis of osteoporotic fracture

PostmenopausalBone loss

Age related bone loss

Low peak bone mass

FRACTURE =Fall + Low BMD

Poor bone quality

(architecture)

Non skeletal factors

(propensity to fall)

LOW BONE MASS Other risk factors

LOW BMD = PBM or Loss

Adapted from Melton LJ & Riggs BL. Osteoporosis: Etiology, Diagnosis and ManagementRaven Press, 1988, pp155-179

Microarchitectural Changes in Osteoporosis

Bone Mass

Trab Thickness

Trabecular Number

Horizontal Struts

Connectivity

Anisotropy

aBMD (areal) = g/cm2

vBMD (volumetric) = g/cm3

BoneQualityBoneQuality

BoneStrength and

MicroarchitectureGeometry/sizeTurnover/Remodeling RateDamage AccumulationDegree of MineralizationProperties of the Collagen/mineral Matrix

Shifting the Osteoporosis Paradigm Bone StrengthNIH Consensus Statement 2000

Sourced from NIH Consensus Development Panel on Osteoporosis. JAMA 285:785-95; 2001

Bone MineralDensity

Alteration in bone structure in untreated postmenopausal women

Dufresne TE et al, Calcif Tissue Int, 2003;73:423-432

Baseline One year after

Hypothetical Effects of Increasing Hypothetical Effects of Increasing Bone MineralizationBone Mineralization

Percentage MineralizationPercentage Mineralization

ResistanceResistance to fracture to fracture forcesforces

Improved resistance to Improved resistance to bending = stiffnessbending = stiffness

Increasing brittlenessIncreasing brittleness

Normal =65%

The Mechanical Consequences of Mineralization

Turner C et al., Osteopor. Int 2002; 13:97.

x

x

x

Displacement

For

ce

Hyper-mineralized (Ostepetrosis)

Optimal

Hypo-mineralized (Osteomalacia)

Tough but not Stiff

Stiff but not Tough

Goal of osteoporosis management:prevention of the first fracture

• Women who have 1 vertebral fracture have an 11-fold increased risk of ever having another vertebral fracture1

• Women with 1or more pre-existing vertebral fractures have an 5.1-fold increased risk of another vertebral fracture within the next year2

1. Melton et al. Osteoporos Int 1999: 10; 214-212. Lindsay et al. JAMA 2001: 285; 320-3

Management of Osteoporosis Management of Osteoporosis Goals of TherapyGoals of Therapy

• Prevent first fragility fracture or future fractures if one has already occurred

• Stabilize/increase bone mass

• Relieve symptoms of fractures and/or skeletal deformities

• Improve mobility and functional status

16

Major bone measurement techniques

Dual-energy X-rayAbsorptiometry (DXA)

Spine, hip, forearm, calcaneus, whole body

Quantitative computedTomography (QCT)

Spine, hip, forearm

Ultrasound attenuation and velocity

Heel, patella, tibiaforearm

High-resolution p-QCT Forearm, tibia

17

WHO criteria for osteoporosis in women

Kanis JA et al, J Bone Miner Res, 1994;9:1137-1141

T-Score

Normal -1 and above

Low bone mass -1 to -2.5

Osteoporosis < -2.5

Established osteoporosis

< -2.5 and one or more fractures

Therapeutic options for osteoporosis

• Stimulators of bone formation = anabolic

• (Fluoride)• ParaThyroid Hormone rhPTH(1-34)= teriparatide

• Mixed mechanism of action• Active Vitamin D metabolites• Strontium ranelate

• Recommended for all women at risk for osteoporosis

• Calcium and vitamin D

Inhibitors of bone resorption= antiresorptives

Bisphosphonates– Alendronate– Risedronate– Ibandronate– Zoledronate

• Calcitonin • Estrogen ± progestin

• Selective estrogen receptor modulators (SERMs)– Raloxifene

Raloxifene

PTH

CalcitoninHRTHRT

HRTHRT

During Hot Flashes

Post Vasomotor SymptomsPre fracture

Post Fracture

Risk of Fracture

AGE

At Risk/Osteopenia Osteoporosis Severe OsteoporosisSTAGE

LowerHigher-2.5BMD (T-score)

Bisphosphonates

Osteoporosis Therapy AlgorithmPostmenopausal Women

Effect of Teriparatide on Structural IndicesQuantitative analysis-Significant changes

Trabecular bone volume

Structure model index

Connectivity density

Cortical thickness

P=0.025

P=0.034

P=0.001

P=0.012

Jiang et al. J Bone Miner Res 2003;18(11):1932-1941

Baseline

2004

Post treatment

Patient treated with teriparatide 20µg

Female, age 65Duration of therapy: 637 days (approx 21 months)

BMD Change: Lumbar Spine: +7.4% (group mean = 9.7 ± 7.4%) Total Hip: +5.2% (group mean = 2.6 ± 4.9%)

Effect of Teriparatide onSkeletal Architecture

Baseline Follow-up Jiang UCSF

Data from Jiang, J Bone Min Res 2003;18(11):1932-1941

I have no mental , sentimental, emotional

and FINANCIAL connection with

Teriparatide

This is what it scientifically does