Prof.Emeritus Khunying Kobchitt Prof.Emeritus Khunying Kobchitt
LimpaphayomLimpaphayom
Past President Thai Osteoporosis Foundation (TOPF)
President of Thai Menopause Society (TMS)
Prof.Emeritus Khunying Kobchitt Prof.Emeritus Khunying Kobchitt
LimpaphayomLimpaphayom
Past President Thai Osteoporosis Foundation (TOPF)
President of Thai Menopause Society (TMS)
Physical sequelaeHeight loss…Back pain…Limited ventilation…Narrow abdominal cavity…Abdominal skin infection…Problem with gait & balance
Mental sequelaePoor self esteem…Social isolation…Depression…
One year after hip fracture
20% Death…30% Permanent disability40% Can’t walk independently80% Can’t do 1 ordinary activity
Rene Rizzoli, 2006
Male
Female
Female/Male Ratio
US (white)
187
535
2.9
Hong Kong
180
459
2.4
Singapore
164
442
2.6
Malaysia
88
218
2.4
Thailand
114
269
2.8
*Adjusted to the 1989 US white population by direct standardization, and presented with US white incidence data for 1988 -1989.
Asian Osteoporosis Study Group, 1998.Asian Osteoporosis Study Group, 1998.
0
10
20
30
40
50
60
70
80
Pat
ien
ts (
%)
Death within One year
Permanentdisability
Unable to carry out atleast one independentactivity of daily living
Unable to walkindependently
One year after a hip
fracture:
20%
30%
40%
80%
Cooper C., Am J Med. 1997;103(2A):12s-19s
Age (yrs.)
90807060504030
1.4
1.2
1.0
.8
.6
.4
.2
Bo
ne
Min
era
l De
nsi
ty a
t L
um
ba
r S
pin
e (
g/c
m2 )
Osteopenia 27.63%Osteoporosis 19.75%
Osteopenia
Osteoporosis
0.847
0.682
Limpaphayom K, et al. Menopause 2001; Vol.8., No.1 : 65-69.
Bo
ne
Min
era
l De
nsi
ty a
t F
em
ora
l ne
ck (
g/c
m2 )
1.4
1.2
1.0
.8
.6
.4
.2
Age (yrs.)
90807060504030
0.716
0.569
Osteopenia
Osteoporosis
Osteopenia 37.4%Osteoporosis 13.6%
Limpaphayom K, et al. Menopause 2001; Vol.8., No.1 : 65-69.
Woman> 55 yr 6.2 m
Woman 31.8 m
Thai Population 63 m.
Osteoporosis1.8 m.
HIP FX269/100,000
National Statistic Office 2003
Phadungkiat S, et alJ Med Assoc Thai 2002;85:565
Age (yrs)Age (yrs)
Ag e
-adj
ust e
d in
cide
n ce
(per
100
, 000
)
0
150
300
450
600
750
900
51-54 55-59 60-64 65-69 70-74 >75
0
20000
40000
60000
80000
100000
0
20000
40000
60000
80000
100000
2198120131
15827
10765720553383716
25271715
741887518174029
70975
66511
61399
55595
46718
35745
2198120131
15827
10765720553383716
25271715
741887518174029
70975
66511
61399
55595
46718
35745
1970 1980 1990 2000 2010 2020 2030 2040 2050 1970 1980 1990 2000 2010 2020 2030 2040 2050
Total populationAging populationTotal populationAging population
United Nations World Population Prospects, The 1998 Revision, Vol. 1,New York: Dept. of Economic and Social Affairs, Population Division, 1999.United Nations World Population Prospects, The 1998 Revision, Vol. 1,New York: Dept. of Economic and Social Affairs, Population Division, 1999.
AP / TP ~ 1 / 3
AP / TP ~ 1 / 12
AP / TP ~ 1 / 20
Estrogen deficiency
Rene Rizzoli, 2006Rene Rizzoli, 2006
Osteoclast lineage Osteoblast lineage
Rene Rizzoli, 2006
RANKL OPG
Stimulation Dexametasone 17 β-Estradiol
1 α,25-(OH2)D3
PTH
PGE2
Inhibition 17 β-Estradiol Hydrocortisone1 α,25-(OH2)D3 PTH
PGE2
Aubin J., Osteoporosis Int. 2000;11(11):905-13
Increased OC formationIncreased OC formationIncreased OC activityIncreased OC activityIncreased OC lifespanIncreased OC lifespanDecreased OB lifespanDecreased OB lifespanDecreased O’cyte lifespanDecreased O’cyte lifespan
Increased OC formationIncreased OC formationIncreased OC activityIncreased OC activityIncreased OC lifespanIncreased OC lifespanDecreased OB lifespanDecreased OB lifespanDecreased O’cyte lifespanDecreased O’cyte lifespan
Estrogendeficiency
Decreased OC formationDecreased OC formationDecreased OC activityDecreased OC activityDecreased OC lifespanDecreased OC lifespanIncreased OB lifespanIncreased OB lifespanIncreased O’cyte lifespanIncreased O’cyte lifespan
Decreased OC formationDecreased OC formationDecreased OC activityDecreased OC activityDecreased OC lifespanDecreased OC lifespanIncreased OB lifespanIncreased OB lifespanIncreased O’cyte lifespanIncreased O’cyte lifespan
Estrogentherapy
Estrogendeficiency
Normal bone Osteoporosis
Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality.
NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95
Normal:BMD is within +1 or -1 SD of the young adult mean.
Osteopenia (low bone mass):BMD is between -1 and -2.5 standard deviations below young adult mean.
Osteoporosis:BMD is -2.5 SD or more than the young adult mean.
Severe (established) osteoporosis:BMD is more than -2.5 SD and one or more osteoporotic fractures have occurred.
*based on DXA measurement at hip or spine
Bone StrengthNIH Consensus Statement 2000
BoneQuality
BoneStrength and
Architecture and geometryTurnover/ remodeling rateDegree of MineralizationDamage AccumulationProperties of collagen/mineral matrix
BoneDensity
NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95
0
200
400
600
800
1000
NorthAmerica
Europe Latin America Asia
19902050
Cooper 1992
3250
Total number of hip fractures 1990 = 1.6 millions2050 = 6.3 millions
(n x
1000
)
Dietary calcium intake Vitamin D intake and synthesis
Calcium absorption Estrogen deficiency
Plasma calcium PTH secretion
Bone turnover and resorption
Low peakbone mass
Postmenopausal Bone loss
Age related bone loss
LOW BONE MASSOther riskfactors
Non skeletalFactors
(propensity to fall) FRACTURE =
Fall + Low BMD
Poor boneQuality
(architecture)
LOW BMD = PMB or Loss
Adapted from Melton LJ & Riggs BL. Osteoporosis : Etiology, Diagnosis and Management Raven Press, 1988, pp155-179
With socio-economic development in many
Asian countries and rapid ageing of the Asian
population, osteoporosis has become one of the
most prevalent and costly health problems in the
region. Unsurprisingly, Asia is the region
expecting the most dramatic increase in hip
fractures during coming decades; by 2050 one
out of every two hip fractures worldwide will occur
in Asia.
OsteoclastOsteoclast OsteoblastOsteoblast
Russell RGG, et al. Current Opinion in Rhematology 2006;18:S3-10.Russell RGG, et al. Current Opinion in Rhematology 2006;18:S3-10.
Established Established drugsdrugs
Established Established drugsdrugs
PotentialPotentialinhibitorsinhibitorsPotentialPotentialinhibitorsinhibitors
BisphosphonatesBisphosphonatesEstrogensEstrogensSERMsSERMsCalcitoninCalcitoninStrontium Strontium
Blocking RANKL Blocking RANKL systemsystem
Cathesin K inhibitorCathesin K inhibitorMevalonate inhibitorMevalonate inhibitorOther inhibitors & Other inhibitors &
antagonistsantagonists
Established Established drugsdrugs
Established Established drugsdrugs
PotentialPotentialstimulatorsstimulatorsPotentialPotential
stimulatorsstimulators
PTHPTHStrontiumStrontium
PGsPGsFluorideFluorideVitamin DVitamin DSclerostin inhibitorsSclerostin inhibitorsAndrogen (SERMs)Androgen (SERMs)BMP-2BMP-2Etc.Etc.
Enhance Enhance PBMPBM
Fall Fall preventionprevention
Prevent bone lossPrevent bone loss
Healthy Healthy lifestylelifestyleHealthy Healthy lifestylelifestyle
AvoidingAvoidingHealth risksHealth risksAvoidingAvoiding
Health risksHealth risks
LifestyleLifestylemodificationmodification
LifestyleLifestylemodificationmodification
PharmacologicalPharmacologicalinterventionintervention
PharmacologicalPharmacologicalinterventionintervention
SelfSelfimprovementimprovement
SelfSelfimprovementimprovement
EnvironmentalEnvironmentaladaptationadaptation
EnvironmentalEnvironmentaladaptationadaptation
Estrogen
Bisphosphonates
Raloxifene
Calcitonin
Parathyroid hormone
Strontium ranelate
~ 50%Risk reduction!
Sambrook P, et al. Lancet 2006;367:2010-18.
Fall & balance
Environmental & Environmental & family factor!family factor!
Physical & mentalPhysical & mentalstrengtheningstrengthening
• Age• Impaired gait or balance; lower body muscle weakness• Poor vision; cataracts• Malnutrition; excessive alcohol intake• Certain medical conditions, e.g. arthritis, diabetes, postural hypotension,
cognitive impairment, peripheral neuropathy• Polypharmacy; certain medications, e.g. psychoactive medications,
antihypertensives • Footwear with slippery soles, high heels• Factors in the home, e.g. poor lighting, loose rugs, loose cabling, uneven
or wet surfaces, bathtubs without handrails or bath mat, clutter at floor level, stepping over pets
• Environmental factors, e.g. wet or cracked paving or steps, ice or snow
1. Lighting : ample, easy switchs, walkways
2. Obstruction
3. Floors & carpets
4. Furniture : chairs, bed height
5. Storage : accessible height
6. Bathroom : grab bars, chairs, toilet seat, nonskid
7. Stairways & halls : handrails, steps, nonskid
8. Human factor : heartfelt care, wheel chair
9. Medication : sedatives
NAMS. Position Statement. Management of Osteoporosis in postmneopausal women 2006. Menopause 2006;13:340-67.
Kannus P, et al. N Engl J Med 2000;343:1506-13.
0
10
20
30
40
50
60
70
80
90
100
0 20 40 60 80 100
Age (years)
% f
ull
hea
lth
Road traffic accident
Colles’ fracture
Vertebral fractures
NORMALNORMALHEALTHHEALTH
FRACTUREFRACTURE
PARTIALPARTIAL RECOVERYRECOVERY
DEATHDEATH
Structure• bone density• microarchiecture
Structure / Function Activities / Participation
Mobility• walking, using transport
Interactions & relationships• spousal, family, work
Symptoms• pain• loss of movement
OSTEOPOROSISOSTEOPOROSISSelf care• washing, dressing
Domestic life• shopping, meals, house
FURTHERFURTHERFRACTUREFRACTURE
Following first distal forearm fracture Cuddihy et al Osteoporosis Int 1999
hip fracture 1.4 fold in women
2.7 fold in men vertebral fracture 5.2 fold in women
10.7 fold in men
Prevalent vertebral fracture and new vertebral fracture in next year Lindsay et al JAMA 2001
1 prevalent fracture RR 2.6 1 RR 5.1 2 RR 7.3
Prevalent vertebral fracture increases risk of hip fracture > 2 fold
NORMALNORMALHEALTHHEALTH
FRACTUREFRACTURE
PARTIALPARTIAL RECOVERYRECOVERY
DEATHDEATH
Acute care• hospitalisation• rehabilitation
Direct Costs Indirect Costs
Attendant care
Opportunity costs of family / carers
Long term• primary care• drugs• further fractures
OSTEOPOROSISOSTEOPOROSIS
Social services
Institutionalisation
1.1. Biology eg., vit D receptor gene, hip axis lengthBiology eg., vit D receptor gene, hip axis length
2.2. Mentality eg., introvert, slow down, peacefulMentality eg., introvert, slow down, peaceful
3.3. Nutrition eg., semi-vegetarian foodNutrition eg., semi-vegetarian food
4.4. Family eg., higher priority, big familyFamily eg., higher priority, big family
5.5. Social status eg., privilege, seniority oriented Social status eg., privilege, seniority oriented
PerceptionHRT should not be used for bone protection because of its unfavorable safety profile. Official recommendations by health authorities (EMEA, FDA) limit the use of HRT to a second-line alternative. HRT could only be considered when other medications failed, were contraindicated or not tolerated, or in the very symptomatic woman.
EvidenceFor the age group 50-59, HRT is safe and cost-effective. Overall, HRT is effective in the prevention of all osteoporosis-related fractures, even in patients at low risk of fracture.
Roussow J. JAMA 2007;297:1465; Cauley JA. JAMA 2003;290:1729Jackson RD. J Bone Min Res 2006;21:817
PerceptionHRT is not as effective in reducing fracture risk as other products (bisphosphonated, etc)
EvidenceAlthough no head-to-head studies have compared HRT to bisphosphonates in terms of fracture reduction, there is noevidence to suggest that bisphosphonates or any other antiresorptive therapy are superior of HRT.
Many people read only headlines or short messages:
For these people, a short take-home message is the following:
The target population for initiation of HRT is usually women up to age
55.
HRT initiated in the early postmenopausal period in healthy women is
safe.
Like all medicines, HRT needs to be used appropriately, but it is
essential that women in early menopause who are suffering
menopausal symptoms should have the option of using HRT.