Osteoporosis ACOG 2004; 50: 203-16. 부산백병원 산부인과 R4 김 성 용

OsteoporosisOsteoporosis

ACOG 2004; 50: 203-16.ACOG 2004; 50: 203-16.

부산백병원 산부인과 부산백병원 산부인과 R4R4

김 성 용김 성 용

OsteoporosisOsteoporosis► Systemic skeletal disease Systemic skeletal disease

Microarchitectural deterioration of bone tissue with a resultant increase in fMicroarchitectural deterioration of bone tissue with a resultant increase in fragility.ragility.

13-18 % of U.S. women over 50 years13-18 % of U.S. women over 50 years Another 37-50% have osteopeniaAnother 37-50% have osteopenia

► Increase the risk of fractureIncrease the risk of fracture Hip Fx. Hip Fx.

► Morbidity and mortality 15-20%Morbidity and mortality 15-20% Thoracic spine Fx.Thoracic spine Fx.

► Morbidity, including painMorbidity, including pain► DeformityDeformity► Loss of indepandenceLoss of indepandence► Reduce of cardiovascular, respiratory, digestive function.Reduce of cardiovascular, respiratory, digestive function.

► Osteoporosis is a largely preventable complication of menopause.Osteoporosis is a largely preventable complication of menopause.

BackgroundBackground

DefinitionDefinition PathophysiologyPathophysiology Factors Affecting Bone MassFactors Affecting Bone Mass Screening MethodsScreening Methods

DefinitionsDefinitions

► Axial skeleton measurement of bone mineral Axial skeleton measurement of bone mineral density.density. Z score or T scores of DXA of lumbar spine or hip.Z score or T scores of DXA of lumbar spine or hip.

► Z scoreZ score Based of standard deviation from the bone Based of standard deviation from the bone

mineral density of a same sex, race, and age.mineral density of a same sex, race, and age.

► T score T score Based on the mean peak bone mineral density of Based on the mean peak bone mineral density of

a normal young adult population.a normal young adult population.

DefinitionsDefinitions

► 1 SD decrease = 2 fold increase of Fx. Risk1 SD decrease = 2 fold increase of Fx. Risk► Peripheral bone T scorePeripheral bone T score

Cannot used WHO classification.Cannot used WHO classification. Used predict of fracture.Used predict of fracture. Osteoporosis screening.Osteoporosis screening. In development.In development.

PathophysiologyPathophysiology► Bone remodeling Bone remodeling

unit : osteoblast, osteoclastunit : osteoblast, osteoclast Cycle is divided into 4 phaseCycle is divided into 4 phase

► Take several months to completeTake several months to complete► Resting Resting

Stem cell from BM are attracted to bone surface and differentiate into osteoclasts. Stem cell from BM are attracted to bone surface and differentiate into osteoclasts. ► ResorptionResorption

Acid pH Acid pH 로 로 mineral mineral 을 을 dissolve , proteolytic enzymes dissolve , proteolytic enzymes 으로 으로 digest the bone proteins. digest the bone proteins. ► ReversalReversal

Osteoclast cease removing bone.Osteoclast cease removing bone. Stem cell attracted to the bone surface, and differentiated into osteoblast.Stem cell attracted to the bone surface, and differentiated into osteoblast.

► FormationFormation Make new bone with protein matrix(osteoid).Make new bone with protein matrix(osteoid). Protein matrix accounts for much of tensile strength.Protein matrix accounts for much of tensile strength. Mineral component provides compressional strength.Mineral component provides compressional strength.

► Cytokine (interleukin 1, 3, 6, 11), growth factor, platelet derived GF, IGF-I,II moduCytokine (interleukin 1, 3, 6, 11), growth factor, platelet derived GF, IGF-I,II modulate osteoclast and osteoblast function.late osteoclast and osteoblast function.

PathophysiologyPathophysiology

► Bone can be divided into 2 major typeBone can be divided into 2 major type Cortical boneCortical bone

►Outer shallOuter shall►75% of total bone mass75% of total bone mass

Trabecular boneTrabecular bone► Internal supportInternal support►Spongy, interlacing network.Spongy, interlacing network.►25% of total bone mass25% of total bone mass►Most of the volume in bone.Most of the volume in bone.►Because of it’s larger surface and higher rate of turnover, it shoBecause of it’s larger surface and higher rate of turnover, it sho

ws early bone loss, and first response to therapy.ws early bone loss, and first response to therapy.

PathophysiologyPathophysiology

► Bone mass Bone mass peaks at age 30 yearspeaks at age 30 years 0.4% lost per year after peak.0.4% lost per year after peak. 2% of cortical bone, 5% of trabecular bone loss per ye2% of cortical bone, 5% of trabecular bone loss per ye

ar for the 5-8 years after menopause. ar for the 5-8 years after menopause. In recently menopause, excess bone loss is commonly In recently menopause, excess bone loss is commonly

caused by excessive osteoclast-mediated resorption.caused by excessive osteoclast-mediated resorption. Later poatmenopausal, suppression of osteoblast actiLater poatmenopausal, suppression of osteoblast acti

vity and inadequate formation of bone play a major rolvity and inadequate formation of bone play a major role of osteoporosise of osteoporosis

Factors Affecting Bone MassFactors Affecting Bone Mass

► Single largest factor is Genetic fSingle largest factor is Genetic factor.actor. Family historyFamily history Caucasian and Asian women > MCaucasian and Asian women > M

exican-American > African-Americaexican-American > African-Americann

► Weight-bearing exercise stimulatWeight-bearing exercise stimulate osteoblastic activity.e osteoblastic activity.

► High dose of corticosteroid(>7.5High dose of corticosteroid(>7.5mg) chronic heparin thrapy(12,0mg) chronic heparin thrapy(12,000-50,000) is associated with b00-50,000) is associated with bone loss.one loss.

► Hyperthyroidism Hyperthyroidism

Factors Affecting Bone MassFactors Affecting Bone Mass

Clinical Considerations and Clinical Considerations and RecommendationsRecommendations

When should screening for osteoporosis be initiated?When should screening for osteoporosis be initiated? Under what circumstances are screening tests other Under what circumstances are screening tests other

than DXA useful?than DXA useful? Can lifestyle changes prevent osteoporosis and Can lifestyle changes prevent osteoporosis and

osteoporosis related fracture?osteoporosis related fracture? Is there a role for estrogen and progestin for the Is there a role for estrogen and progestin for the

prevention or treatment of osteoporosis?prevention or treatment of osteoporosis? When estrogen therapy is discontinued, how should a When estrogen therapy is discontinued, how should a

woman be monitored for osteoporosis risk?woman be monitored for osteoporosis risk? Is other pharmacotherapy beneficial for the prevention Is other pharmacotherapy beneficial for the prevention

and treatment of osteoporosis?and treatment of osteoporosis? Are complementary and alternative therapies beneficial Are complementary and alternative therapies beneficial

for the prevention of osteoporosis?for the prevention of osteoporosis? When should treatment for osteoporosis begin and how When should treatment for osteoporosis begin and how

should patients be followed?should patients be followed?

When should screening for osteoporosis When should screening for osteoporosis be initiated?be initiated?

► Guidelines of testing bone mineral densityGuidelines of testing bone mineral density All postmenopausal women aged 65yrs or older.All postmenopausal women aged 65yrs or older. Post menopausal women younger than 65yrs who have 1 or more risk factorPost menopausal women younger than 65yrs who have 1 or more risk factor All postmenopausal women with fracture to confirm the diagnosis of osteoporosis anAll postmenopausal women with fracture to confirm the diagnosis of osteoporosis an

d determine disease severity.d determine disease severity.► National Osteoporosis Foundation : postmenopausal women aged 50-60 with riNational Osteoporosis Foundation : postmenopausal women aged 50-60 with ri

sk factors or 60-65yrs with or without R/F.sk factors or 60-65yrs with or without R/F.► Premenopausal women with certain disease or medical conditionsPremenopausal women with certain disease or medical conditions► For making decision about prevention therapy of early menopausal women.For making decision about prevention therapy of early menopausal women.► Without new risk factor, not be performed more frequently than every 2 years.Without new risk factor, not be performed more frequently than every 2 years.► Vertebral Fx. Vertebral Fx. 가 있는 가 있는 order, menopausal women order, menopausal women 에게는 에게는 bone mineral density bone mineral density

test test 없이도 치료를 시작해야 하지만 없이도 치료를 시작해야 하지만 nonvertebral Fx.(hip or wrist) nonvertebral Fx.(hip or wrist) 의 경우는 의 경우는 반드시 검사를 시행하고 적응증에 맞을때 치료를 시작해야 한다반드시 검사를 시행하고 적응증에 맞을때 치료를 시작해야 한다 ..

Under what circumstances are screening tests other Under what circumstances are screening tests other than DXA useful?than DXA useful?

► Peripheral bone densinometryPeripheral bone densinometry Less expensive, portable, reasonable precision, and low radiation exposure.Less expensive, portable, reasonable precision, and low radiation exposure. Screening tools in the evaluation of bone loss, but cannot replace DXA scan Screening tools in the evaluation of bone loss, but cannot replace DXA scan

for prediction of hip Fx. And the diagnosis of osteoporosis.for prediction of hip Fx. And the diagnosis of osteoporosis.► Quantitative UltrasonographyQuantitative Ultrasonography

Provides information on bone elasticity and structure in peripheral sites.Provides information on bone elasticity and structure in peripheral sites. Advantage : low cost and lack of radiation.Advantage : low cost and lack of radiation.

► Peripheral Quantitative Computed TomographyPeripheral Quantitative Computed Tomography Ability to distinguish cortical form trabecular bone.Ability to distinguish cortical form trabecular bone. Early and more precise assessment of skeletal change, due to quick changEarly and more precise assessment of skeletal change, due to quick chang

e of trabecular bonee of trabecular bone More expensive and more radiationMore expensive and more radiation Less dataLess data

Under what circumstances are screening tests Under what circumstances are screening tests other than DXA useful?other than DXA useful?

► Biochemical Makers of BonBiochemical Makers of Bone Turnovere Turnover Cannot diagnose osteoporosiCannot diagnose osteoporosi

s, predict bone density or fras, predict bone density or fracture risk.cture risk.

Useful to help identify womeUseful to help identify women with high bone turnover.n with high bone turnover.

Assessment of theraputic reAssessment of theraputic response (earlier than bone misponse (earlier than bone mineral density change)neral density change)

Very expensive.Very expensive.

Can lifestyle changes prevent osteoporosis Can lifestyle changes prevent osteoporosis and osteoporosis-related fracture?and osteoporosis-related fracture?

► Weight-bearing exercise stimulate osteoblast to form new bWeight-bearing exercise stimulate osteoblast to form new bone.one. Persist only when exercise is continued.Persist only when exercise is continued. For 22 months, 6.1% of bone density of lumbar vertebrae increasFor 22 months, 6.1% of bone density of lumbar vertebrae increas

e observed in postmenopausal women.e observed in postmenopausal women.► Disease and sensory impairments that can cause falling shDisease and sensory impairments that can cause falling sh

ould be treated.ould be treated. Medications, living environment should be monitored.Medications, living environment should be monitored.

► Cessation of smoking, reducing alcohol intakeCessation of smoking, reducing alcohol intake Alcohol(7 oz or more per week) increase the risk for both fall and Alcohol(7 oz or more per week) increase the risk for both fall and

hip fracture and has detrimental effect on bone mineral density.hip fracture and has detrimental effect on bone mineral density. Moderate alcohol is associated with increased mineral bone denModerate alcohol is associated with increased mineral bone den

sity. (it is not clear why this occur)sity. (it is not clear why this occur)

Is there a role for estrogen and progestin for Is there a role for estrogen and progestin for the prevention or treatment of osteoporosis?the prevention or treatment of osteoporosis?

► Conjugated equine estrogen(0.625 mg/d) with medroxyprogesterone acetate(2.Conjugated equine estrogen(0.625 mg/d) with medroxyprogesterone acetate(2.5 mg/d) reduced the risk of hip and vertebral Fx by 34%, overall Fx by 24%.5 mg/d) reduced the risk of hip and vertebral Fx by 34%, overall Fx by 24%.

► Lower dose combinations of conjugated equine estrogen(0.3 mg/d) with medroxLower dose combinations of conjugated equine estrogen(0.3 mg/d) with medroxyprogesterone acetate(2.5 mg/d) increased bone density 3.5-5.2% in postmenoyprogesterone acetate(2.5 mg/d) increased bone density 3.5-5.2% in postmenopausal(order than 65 yrs).pausal(order than 65 yrs).

► Other studyOther study 0.3mg of oral esterified estrogens0.3mg of oral esterified estrogens Transdermal 17B-estradiol 0.025-0.1 mg per dayTransdermal 17B-estradiol 0.025-0.1 mg per day

► Optimal time to initiate therapyOptimal time to initiate therapy Not determinedNot determined Believed work best in the first 5-10 years after menopause.Believed work best in the first 5-10 years after menopause. A study shows order (mean 76 yrs old) women therapy increased bone density.A study shows order (mean 76 yrs old) women therapy increased bone density. Therapy discontinued, bone turn over and bone loss accelerated, then approaches thTherapy discontinued, bone turn over and bone loss accelerated, then approaches th

at of not treated.at of not treated.► Risk of long-term useRisk of long-term use

Increase the risk of cardiovascular and breast cancer.Increase the risk of cardiovascular and breast cancer.

When estrogen therapy is discontinued, how should a When estrogen therapy is discontinued, how should a woman be monitored for osteoporosis risk?woman be monitored for osteoporosis risk?

►Same as early stage of menopause.Same as early stage of menopause.►Based on age and other risk factorBased on age and other risk factor

Is other pharmacotherapy beneficial for Is other pharmacotherapy beneficial for the prevention and treatment of the prevention and treatment of

osteoporosis?osteoporosis?► 2 categories 2 categories

Bisphosphonates (ie, alendronate, risendronate)Bisphosphonates (ie, alendronate, risendronate)►Inhibit osteoclast activityInhibit osteoclast activity►Both spine and hipBoth spine and hip►Reduce Fx. 30-50%Reduce Fx. 30-50%►Upper G-I S/E and very poor absorption(less then 1%)Upper G-I S/E and very poor absorption(less then 1%)

Take on empty stomachTake on empty stomach With only waterWith only water Remain upright at least 30 min.Remain upright at least 30 min. No additional food or drink during this period.No additional food or drink during this period. Used when established disease.Used when established disease.


osteoporosis?osteoporosis?► Selective estrogen receptor modulators (SERMs) (ie, raloxifene, tibolone, tamoxiSelective estrogen receptor modulators (SERMs) (ie, raloxifene, tibolone, tamoxi

fen)fen) Mixed estrogenic and antiestrogenic property depending on tissue.Mixed estrogenic and antiestrogenic property depending on tissue. Estrogen like effect on skeleton bone density and to reduce fracture without stimulatiEstrogen like effect on skeleton bone density and to reduce fracture without stimulati

ng endometrial and breast tissue.ng endometrial and breast tissue. RaloxifeneRaloxifene

► Reduce 35-50% vertebral Fx.Reduce 35-50% vertebral Fx.► S/E – vasomotor symptoms (hot flush, night sweat)S/E – vasomotor symptoms (hot flush, night sweat)

- DVT - DVT TiboloneTibolone

► Reduce Fx riskReduce Fx risk► Androgenic effect on sexual functionAndrogenic effect on sexual function► Progestational effect on the endometrium.Progestational effect on the endometrium.

TamoxifenTamoxifen► Used as estrogen receptor positive breast ca. and for chemo prevention of breast ca.Used as estrogen receptor positive breast ca. and for chemo prevention of breast ca.► Reduce Fx risk .Reduce Fx risk .► Increase vasomotor Sx.Increase vasomotor Sx.► Stimulate endometrium.Stimulate endometrium.► Incerase venous thrombosisIncerase venous thrombosis


osteoporosis?osteoporosis?► Salmon calcitonin is available for osteoporosis treatment.Salmon calcitonin is available for osteoporosis treatment.

S.C. inj. or nasal sprayS.C. inj. or nasal spray Reduce lumbar spine Fx(36%) at a dose 200U per day, but did not reduce hip Fx.Reduce lumbar spine Fx(36%) at a dose 200U per day, but did not reduce hip Fx. Reduce bone turnover, but bone density change are small(1 %).Reduce bone turnover, but bone density change are small(1 %). Reduce bone pain of osteoporotic compression Fx.Reduce bone pain of osteoporotic compression Fx. S/E : nausea, local inflammation(inj.), flush of face and hands, nasal irritation.S/E : nausea, local inflammation(inj.), flush of face and hands, nasal irritation.

► Recombinant human PTHRecombinant human PTH Increase trabecular bone density and connentivity.Increase trabecular bone density and connentivity. Use in case of failed response to other therapy or very severe disease.Use in case of failed response to other therapy or very severe disease. Reduce vertebral Fx 53-54%.Reduce vertebral Fx 53-54%. Expensive and needs daily injection.Expensive and needs daily injection. PTH is significantly reduced when co-administration with bisphosphonates; therefore, PTH is significantly reduced when co-administration with bisphosphonates; therefore,

they should not be combined.they should not be combined.► Fluoride increase bone brittleness and propensity to fracture.Fluoride increase bone brittleness and propensity to fracture.► Testosterone effect is not clear.Testosterone effect is not clear.


osteoporosis?osteoporosis?► Combinations of Antiresorptive TCombinations of Antiresorptive T

herapiesherapies Addition of progesterones, additiAddition of progesterones, additi

on of androgens can have addition of androgens can have additive effect on bone mineral densitve effect on bone mineral density.y.

Risedronate, alendronate and raRisedronate, alendronate and raloxifen loxifen 은 실험으로 병용 시 은 실험으로 병용 시 bobone mineral density ne mineral density 증강증강 (1-3%)(1-3%)의 효과가 있음이 입증됨의 효과가 있음이 입증됨 ..

이 결과가 이 결과가 fracture protection fracture protection 에도 효과적인지는 아직 밝혀진 에도 효과적인지는 아직 밝혀진 바 없음바 없음 ..

Calcium and vit.D should be conCalcium and vit.D should be considered adjuvant therapy for indisidered adjuvant therapy for individual.vidual.

Are complementary and alternative therapies Are complementary and alternative therapies beneficial for the prevention of osteoporosis?beneficial for the prevention of osteoporosis?

► Isoflavones (a class of phytoestrogens found in rich supply iIsoflavones (a class of phytoestrogens found in rich supply in soybeans and red clover) studies has not demonstrated a n soybeans and red clover) studies has not demonstrated a reliable positive effect on bone density, bone turnover markreliable positive effect on bone density, bone turnover marker, or fracture risk in woman with osteoporosiser, or fracture risk in woman with osteoporosis

When should treatment for osteoporosis begin When should treatment for osteoporosis begin and how should patients be followed?and how should patients be followed?

► T score 1 SD decrease = 10-12% change in bone T score 1 SD decrease = 10-12% change in bone mineral density.mineral density.

► Low risk of fracture in young women with osteopeniLow risk of fracture in young women with osteopenia a High cost long term side effect led to suggest withholdHigh cost long term side effect led to suggest withhold

ing treatment until certain theraputic threshold have bing treatment until certain theraputic threshold have been reached.een reached.

► The National Osteoporosis Foundation The National Osteoporosis Foundation T score -2 without risk factorT score -2 without risk factor T score -1.5 with risk factorT score -1.5 with risk factor

When should treatment for osteoporosis begin When should treatment for osteoporosis begin and how should patients be followed?and how should patients be followed?

►Monitoring of treatment requires central bonMonitoring of treatment requires central bone densinometry.e densinometry. Precision : 2-3%Precision : 2-3% Repeat DXA testing Repeat DXA testing

►untreated post menopausal untreated post menopausal 은 은 per 3-5 yearsper 3-5 years►Treatment Treatment 받는 동안은 치료의 효과를 받는 동안은 치료의 효과를 monitor monitor 하기 하기

위해 위해 22 년 마다 한번씩 시행한다년 마다 한번씩 시행한다 ..►4-5% 4-5% 의 의 mineral density loss mineral density loss 가 있을 때는 치료의 가 있을 때는 치료의

방법을 변화하는 것이 필요하다방법을 변화하는 것이 필요하다 ..

Summary of Summary of RecommendationsRecommendations

► Recommendations based on good and consistent scientific Recommendations based on good and consistent scientific evidence (Level A)evidence (Level A) Treatment should be initiated to reduce fracture risk in postmenoTreatment should be initiated to reduce fracture risk in postmeno

pausal women who have experienced a fragility or low-impact fracpausal women who have experienced a fragility or low-impact fracture.ture.

T scores less than -2 by central DXA in the absence of risk factor T scores less than -2 by central DXA in the absence of risk factor and less than -1.5 with 1 or more risk factor.and less than -1.5 with 1 or more risk factor.

First-line pharmacologic options determined by the FDA to be safFirst-line pharmacologic options determined by the FDA to be safe and effective for osteoporosis prevention (bisphosphonate [alee and effective for osteoporosis prevention (bisphosphonate [alendronate and risedronate], raloxifene, and estrogen) should be undronate and risedronate], raloxifene, and estrogen) should be used.sed.

First-line pharmacologic options determined by the FDA to be safFirst-line pharmacologic options determined by the FDA to be safe and effective for osteoporosis treatment (bisphosphonate [alene and effective for osteoporosis treatment (bisphosphonate [alendronate and risedronate], raloxifene, calcitonin, and PTH) should dronate and risedronate], raloxifene, calcitonin, and PTH) should be used.be used.

Summary of Summary of RecommendationsRecommendations

► Recommendations based on limited or inconsistent evidence (Level B)Recommendations based on limited or inconsistent evidence (Level B) Women should be counseled about the following prevention measuresWomen should be counseled about the following prevention measures

► Adequate calcium consumption, using diatary supplements if dietary sources are Adequate calcium consumption, using diatary supplements if dietary sources are not adequatenot adequate

► Adequate vit.D consumption(400-800 IU per day)Adequate vit.D consumption(400-800 IU per day)► Regular weight-bearing and muscle-strengthening exercisesRegular weight-bearing and muscle-strengthening exercises► Smoking cessationSmoking cessation► Moderation of alcohol intakeModeration of alcohol intake► Fall prevention strategiesFall prevention strategies

Bone mineral density testing should be recommended Bone mineral density testing should be recommended ► to all postmenopausal women over 65 yrsto all postmenopausal women over 65 yrs► To younger than 65 yrs with risk factorTo younger than 65 yrs with risk factor► To all menopausal women with fracture to confirm the diagnosis of osteoporosis To all menopausal women with fracture to confirm the diagnosis of osteoporosis

and determine disease activityand determine disease activity Screening should not be performed more frequently than every 2 yrs without Screening should not be performed more frequently than every 2 yrs without

new risk factors.new risk factors.

Documents

Osteoporosis ACOG 2004; 50: 203-16. 부산백병원 산부인과 R4 김 성 용