Update on Osteoporosis
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Transcript of Update on Osteoporosis
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
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