骨粗鬆症の予防と管理

(1)

大阪市立大学名誉教授

森井浩世 ^監訳

骨粗鬆症の予防と管理

WHOテクニカルレポート

医薬ジャーナル社

日本語版付記日本の立場から〜治療薬の評価について〜

(2)

!"# $ !"#$%&'()*

!"#$%

! ! !"#$%&' ! !" !#$%&'

!"#

!"!"#$%

!"#$%

!"#$%&

!"

!"#$%&

!"

!

(3)

Chairman

Vice-

Chairman

Joint

Rapporteur

Joint Rapporteur

Secretary

(4)

(5)

(6)

(7)

!"

!"#$%&'(

!"#$%&#' ! !"#$%

! !

!"#$

!"#$%&

(8)

!""

!"#

!"

!"#$

!" #

女性

0 500 1,000 1,500 2,000

大腿骨近位部骨折（1,000人）

1950 1965 1980 1995 2010 2025

男性

1950 1965 1980 1995 2010 2025 年代

ROW 北米欧州アジア

WHO 03. 155

(9)

!"#$%&

!"#

! "#$

!"#

! "#!

! !"#

!"#$

!

(10)

!"#$%

!"

0 大腿骨近位部

骨折

糖尿病慢性閉塞性

肺疾患

心筋梗塞乳癌

10 20 30 40 50

WHO 03. 156

入院総日数︵単位千日

︶

!"#

!"#$%

!"#$%&'()

(11)

!"#

!"#$

!"#$%&'()*+,-

!"#$%

(12)

!"#$%&'(

!"# $ !" #$

!"#$

!"#

!"#$%

!"

! "

!"#

! !"# $%&

!"

!"#$

!"

!"#$

!"

(13)

!

!"

!"#$%

! "

!"#$

!" # !

The World Health Report 1997. Conquering suffering, enriching humanity

Fifty-first World Health Assembly, Geneva, 11-

16 May 1998

Osteoporosis International

American Journal of Medicine

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a

WHO Study Group

The sex and age distributions of population. The 1994 revision of the United Nations global population esti-

mates and projections.

Os- teoporosis International

Osteoporosis Interna-

tional

Annals of Internal Medicine

Archives of Internal Medicine

Journal of Clinical Epidemiology

(14)

Osteoporosis Inter-

national

tional

Bone

Facts and research in gerontology

Bone

Journal of Bone and Mineral Research

Bone

Journal of the American Geriatrics Society

American Jour-

nal of Epidemiology

Annals Chirurgiae et Gynaecologiae

British Journal of Rheumatology

American Journal of

Medicine

Osteoporosis in the Netherlandsa burden of illness study

Journal of Bone Mineral Research

(15)

!"#$%&'(

!"#

!"#$%

(16)

!"#$

!"#$%&'(

!"#$

!"#

!"# $ !"

!"#$%

!"#$%&'(

!"#$%

!"#$

!"#$%&'

!"#$

!"#

! "

(17)

!"

!"#$%&

!"

! "#

!"#$

!"#$%&' !"#

!"#$!

!"

!"#

!

!"#

!"#$%

!"#$%&

(18)

!"#$%

!"#$%&'(&)*+

!

!"

! ! !"#$%&

!"

!" #$

!"#$

(19)

!" !#$

!"#

cbfa1 osf2

!

in vitro

in vivo

!"#

!"#$%&

!"#$

!"#

(20)

!"#$

!"#

!"

!"#$%

! !"

!"#$%&

!"#$%&'!"#$() !"

in vivoin vitro

(21)

!"#

!"

!

!"#$%

!"#

!"#$%

!"#

!"#$%&' !"#$%&'() !"#$%

(22)

!

!"#$%&

!"#$

!"

!"#$%&

!"#$%

!"

!"#$%&

!"#$

COLIal

!"#$

!"#

!"

(23)

!"#

!"# $

!"#$

!"#$%&' !"#$% &

!"#$%&

!

!"#$%&' !"#$%&

!"#$%

!"#$%&'(

!"

!"#

!"#$%&

(24)

!"#

!

!"!

!"#$

!"#

!" #$

!"#$

! "

!"

!"#$%&' !"#$%&'(

!"# $ !"#$%

!"#$%

!"

(25)

!"#$%& '

!"

in vitroin vivo

!"#$

!"#$%&

!"#$%

!"

!"#$%

!"#$

!"#$%&'

(26)

!"#$

! "

!"#$

!"#

!"#$%

!"#$%&

!"

!"#

!"#$%&'"(

!"#$!

!"#$%

!"#

!

!"

(27)

!"#$#

!"#$

!

!"#$%

!

!"#

Osteoporosis

Osteoporosis

Bisphosphonates in bone disease. From the laboratory

to the patient

(28)

Osteoporosis

Principles of bone biology

Endocrinology & Metabolism Clinics of North America

Princi-

ples of bone biology

Kidney International

Principles of

Bone Biology

Bone

Osteoporosis

Revue du Rhuma-

tismeEnglish Edition

Primer on the metabolic bone

diseases and disorders of mineral metabolism

Disorders of Bone and Mineral Metabolism

Osteoporosis

Trends in Endocrinology &

Metabolism

New England Journal of Medicine

Science

Bone

Endocrine Reviews

(29)

Osteoporosis

Journal of Clinical Investigation

Current Opinion in

Cell Biology

Cell

Genes and Development

Osteoporosis

Princi-

ples of Bone Biology

Primer on the metabolic bone diseases and disorders of mineral metabolism

News in Physiological Science

Primer on

the metabolic bone diseases and disorders of mineral metabolism

WHO Study Group

Euro-

pean Journal of Radiology

Osteoporosis

Journal of Bone & Joint Surgery

Calcified Tissue International

JAMA

American

(30)

Journal of Physical Anthropology

American Journal of Physical An-

thropology

Osteoporosis

Jour-

nal of Clinical Endocrinology & Metabolism

Current Opinion in Rheumatol-

ogy

Journal of Bone and Mineral

Research

Trends

in Endocrinology & Metabolism

Journal of

Bone and Mineral Research

Nutrition and bone development

Pediatric endocrinologyPhysiology, pathophysiology, and clinical aspects

New England Journal

of Medicine

European Journal of Endocrinology

Osteopo-

rosis International

New England Journal of Medicine

Endocrinology

Lancet

(31)

New England Journal of Medicine

Osteoporosis

Os-

teoporosis

Bone

Osteoporosis

Osteoporo-

sis International

(32)

! !"#

!"

!"#$%&

!"

!"#$

!

(33)

!"#$%

!"

!

160 140 120 100 80 60

30 40

BMC BMC/LBM

50 60 70 80 30 40 50 60 70 80 年齢（歳）

男性女性

WHO 03. 157

!"#

!"

(34)

! !"#$%&

!"#$%

!

!"

!"#

(35)

!"#

!

!"#$

!" #

4,000

3,000

2,000

1,000

大腿骨近位部

椎体

Colles

男性女性

35〜39 ≧85

年齢

≧85 10

万人当たりの年間発生率

WHO 03. 158

!

(36)

!"

!"#$!"%&

!"#

!"#$%&' !"#$%

!

!"#$

!"#$%

!"

!"#$%

(37)

!"#

!"

!"#$%

!"#

!

!"#

(38)

!"#$

!"#$%

!"#$%&

!"#$%

!"#$

!"

!"#$%&

! !"#$

!"#$

! ! !" # !"#$%

!"#$%&

!"

! !

(39)

! !"#$%

!"

!"#$%

!"#$ %&'() ! !

!"#$

(40)

!"

!

(41)

!"# $

!"#$

!"#$%

!"#$

!"#

!

!"#

!

! !"

!" #$"

(42)

!"#$%&

!"#$%

!" # !"#$

!"

! !"#$

!

!"#

!"#$%&' !"#"$%&

!"

!"#$%&'(

!"#$

!"#$%&'!

(43)

!"

!"#

!"

! !

!"#$%&

!"#

!"

!"#$

!"#

!"#$

(44)

!"#$%&'()*+,- !"#

!"#$

(45)

!"

!"#$%&

!"#$

!"

(46)

!"#$%

!"#$%&' !"#$%

!"#$

Osteoporosisetiol-

ogy, diagnosis, and management

Danish Medical Bulletin

Osteoporosis Inter-

national

tional

Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of the

WHO Study Group

(47)

Journal of

Osteoporosis

International

Age and Ageing

Trends in Endocrinology and Metabolism

International Journal of Epidemiology

Journal of Bone and Min-

eral Research

Epidemiology

Archives of

Internal Medicine

Journal of the American Geriatrics Society

American Journal of Epidemiology

Epidemiology

Archives of Orthopedic and Trauma Surgery

Singapore Medi-

cal Journal

(48)

Journal of American Medical Association

Osteoporosis

British Medical Journal

Medical Journal of Australia

International Journal of Epidemiology

Lancet

New England Journal of Medi-

cine

Osteoporosis

Journal of the American Medical Association

Annals Inernal Medicine

Canadian

Medical Association Journal

(49)

Journal of Bone and

Mineral Research

Acta Orthopaedica Scandinavica

Osteoporosis

Journal of Bone and Mineral

Research

Bone,

Journal of Nutrition

OsteoporosisClinical guidelines for prevention and treatment

Trends in Endocrinology and Metabolism

Osteopo-

rosis International

Nutritional Aspects of Osteoporosis ' 94. Challenges of Modern Medicine

Nutrition

Bone

Osteoporosis

(50)

Os-

teoporosis

Journal of Clinical Endocrinology and Me-

tabolism

Osteoporosis

Journal of

Journal of Bone and Mineral Re-

search

Osteoporosis

Archives of International Medicine

Osteoporosis.

(51)

!"

!"#$%

!"

!"#$%&'() !"# $"%&'()*

(52)

!"#$

!

! "

(53)

!"#$%&

!"#

!"

!"#

!"

!"#$

(54)

!"#

!"

!"#$%&

!

! !"#$%&

!"#$%&

!"#

!"#$%

!"

!"#$%&

! !

!"#

(55)

!"#$%&

!"#

!"

!"#$

!"#$%

!"#$%&'(

!"#

!"#$%&'($)*

!"#$

!"#

!

(56)

!"#$

!"#$%

!"#$

0.6

骨粗鬆症骨量減少正常

15 50 85 ＞99

−4 −3 −2 −1 0 1 2 3 4

BMD（SD 単位または Tスコア）

集団のパーセント

WHO 03. 160

!"#!$%&

(57)

年齢（歳）

50

50〜59

60〜69

70〜79

80＋

−4 −3 −2 −1 0 1 2 3 BMD（SD 単位）

WHO 03. 161

!"#$%&

(58)

!" #$

!"#$%

!

! !"

!"#$%

!

(59)

!"#

!"#$%&' !"#$

!

(60)

!"#$

! !"#$

! !"

!"

!" # ! !"#

!"#$%&'(

(61)

! !"#$%

!"#$

!"

!"#$%&' !

!"#$

!

(62)

!"

!"#

! !"#

!"#$%

!" # !"#

12

10

8

6

4

2

0

Ⅳ

Ⅲ

Ⅱ

Ⅰ

４分位 WHO 03. 162

大腿骨近位部骨折血圧・脳卒中

コレステロール・心筋梗塞

相対リスク

! !"#$%

(63)

!" #

!"

! !"#$%

!"#$%&

!"

!"#

!" #$%&

! !"#

!"#$%&'

!"#$%

! !"#

!

(64)

!"#

!

!"#

!"#$%&

!"#

!"#$%

!"

!"#$

!

!"#$%&

!"#$

! !"

!

(65)

!"#$

!"#

!"# $ !"#

!"#$

! "#

! !"#$%&'()

(66)

!"#

!"

!"#

!

(67)

!"#$

!"#$%&'(

!"#

!"#$%

!"#

!"#$%&

!"#$%&'

!"#$%&'()

(68)

!"#$!

!

!"#$

! !"

50

40

30

20

10

0

0.6 0.7 0.8 0.9 1.0 1.1 1.2 生涯骨折発生率（％）

骨粗鬆症骨減少

大腿骨頸部 BMD（g/cm²）正常

−3 −2 −1 0 ＋1

（Ｔ値）

WHO 03.163

!"

!

(69)

!"#$%&

!"#$

!"#

!"#$%

(70)

!"#$

!"#

!" #$

!

(71)

! !"#$%&'

!

(72)

!

!"

!"#$%

!"#$

70

60 50 40 30 20 10 0

70 60

50 80 50 60 70 80

年齢（歳）

1.0 2.0 3.0 4.0 5.0 6.0 相対リスク

（％）

男性女性

WHO 03.164 10年

間大腿骨近位部骨折危険率

!"# $%&'

(73)

!"#

!"#$%

!"#

! "

!"#$%&'

!"#$%

!"#

!"#$%&

!"#$%

(74)

!"#

!

!"#$%

!"#$

!"

70 80

60 50

アルゼンチン

70 80 60

50

香港

年齢（歳）

70 60 50

70 80 60

50 40 30 20 10

スウェーデン生涯骨折発生率（％）

WHO 03.165 RR 1 RR 2 RR 3 RR 4 RR 5 RR 6

!" #

(75)

!"#$%&

! !

!"#

Osteoporosis In-

ternational

(76)

British

Medical Journal

Lancet

Bone

Radi-

ology

Lancet

Osteoporosis

WHO Study Group

Osteoporo-

sis International

Cal- cified Tissue International

Journal of Clinical Densitometry

search

(77)

Journal of Clinical Densi-

tometry

Current Rheumatology Reports

Quarterly

Journal of Medicine

Lancet

Bone

Textbook of osteoporosis

Osteoporosisetiology, diagnosis and management

New England Journal of Medi-

cine

Clinical Endocrinology

(78)

Clinical Endocrinology

Bone

Pharmacoepidemiologic risk evaluation in bone diseases

Journal of American Geriatric Society

Bone and Mineral

Age and Ageing

Cal- cified Tissue International

Lancet

Osteoporo-

sis International

Clinical guidelines for the prevention and treatment of osteoporosis

search

Bone

(79)

Biochemical markers of bone metabolism

British Medical Jour-

nal

Trends in Endocrinology & Metabolism

Bone

Osteoporosis.

New perspectives on causes, prevention and treatment

Bone

tional

(80)

! !"#$

!"#$%

! !"

! !"#$%

!"#$%

! !"#

!"#$

!

(81)

! ! !"

!"#$

!"#$%&

!"#$%

!"#

!"#$%&'!

!"#

!"#$

!"#$%

!"

!"#$%&

!"#

!"

!"#

(82)

!"#

!"#$

!"#$%

!"

(83)

!"#

!"

!"#

! !"#$%&

!"#

!"

!"#$

!"#$%

!"#$%&'(

!"

!"#$

!"

!"#$%

!"#$%&'

(84)

!"#$%%

!"

! !"#$%&'

! "#$

!"#$%&'(

!"

!"#

!"#$%

!"#$%&

!"#$%"&

!"#$%&

!

(85)

(86)

!"#

!"#$

! !"#$

!"#

!

!"#$%&'()

!"#$

!"#$%&'()*'+,- !"#$%&'(

(87)

!"#$%&'(

!"

!"#$%&

!"#$

!"

!"#$

!"#$%&

!"#$%

!"#$

!"#$%& '

!"

!"#$%&

!

!"#

!"#$%

!"

!

(88)

!"#$%&'() !"

!"#$

!

!"#

!"#$%&' !

!"#$%&'()*

!"#$%&

!"

!"#$%

!

(89)

!"#$%&

!"#$%

!"#$%&

!"

!"#$%&

! !"#

!"#$%

!"

!"#$%&

!"

!"#

!"#$

!"#$%&

!"

!"#$

(90)

! !"#$%&'(

!"#$%

!

!"#$%

!"#$%&'

!

!"

(91)

!"#$

!

!"#$%

!"

!"#

!"#$%&' !"

!"#$%&

!"#$

!"#$%&

!"#$%"&

! ! !"#$

!"#!

! !"#$

!"#$%&'

(92)

!"#

! !"#$%

!"#$

!"

!

!"#$%&'()

!"#$

!"#$%$

!

! "#

! !"

!"

!"#$%&'() !"#$

!"

!

(93)

! !"#$%&'(

!"

!" #

!"#$%&'

!"#$%&

! !"#$%&'(

!"

!"#$%

!""

!"#

!"#$%&

!"#$%

!

!"#$%&'

(94)

!"#

!"#$%&'(

!"

!"# $ ! !"#$%&

!"#$%&'()*

!"#

!"#$%&'(

!" #$

!

!"#$%&

!"#$

!

!"#$

!"#

(95)

!"

! "#$

!" # !"#

!"#$%

!"#$%&

!"#

!"#$

!

! !"#$%&

! !"#$%

!"#$%

!"#$%&

!"

(96)

!"#$%&'()*

!"#$

!"#

!"

!

!"

!"#$%&

(97)

!"#

!

!"#

!

!"#

!

!"#$%&

! !"

!"

!"#$

(98)

! !"#

!"#$

!"#$%

!"#$%&

!"#$

In vivo

!"#$%

!"#

!"# $ !

!

! !"#$%&'

(99)

!"#$%&' !

!" # !"#$

!"#

!"#$

(100)

!"#

!"

!"#

!"#$%

!"#

!

!"#$

!"

!"#

Journal of Pediatrics

Journal of

British Journal of Nutrition

American

Journal of Public Health

(101)

Pediatrics

JAMA

American Journal of Clinical Nutrition

American Journal of Clinical

Nutrition

Acta Paediatrica

Nutrition

Journal of Clinical Endo-

crinology and Metabolism

Endo-

crine Reviews

(102)

Report on osteoporosis in the European Community

Nutrition Reviews

New England

Journal of Medicine

American Journal of Hyper-

tension

Lancet

Journal of Clinical Endocrinology & Metabolism

Age and Ageing

Calcified Tis-

sue International

British Medical

Journal

Nutritional aspects of osteoporosis ' 94. Challenges of modern medicine

(103)

Journal

of Gerontology

Principles of geriatric medicine

and gerontology

Bone

Lancet

Journal of the American College of Nutrition

Ameri-

can Journal of Clinical Nutrition

Annals of In-

ternal Medicine

Journal of Applied Physiology

Journal of Epidemiology and Community Health

(104)

Annals of Internal Medi-

cine

Annals of Inter-

nal Medicine

Lancet

Obstetrics and Gynecology

An- nals of Internal Medicine

Maturitas

JAMA

Journal of Clinical Endocrinology and Metabolism

JAMA

Lancet

Journal

of Clinical Endocrinology and Metabolism

骨粗鬆症の予防と管理

森井 浩世 監訳