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.