Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3038_Библиотеки_им_академика_М_И_Перельмана
.pdf
POSTMENOPAUSAL OSTEOPOROSIS
R. Civitelli
Division of Bone and Mineral Diseases
Washington University School of Medicine
216 S. Kingshighway Blvd
St. Louis, MO 63110
USA
V. Deregowski
Department of Research
Saint Francis Hospital and Medical Center
Hartford, CT 06105
USA
S. Detaddei
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
A. Diez-Pérez
Autonomous University of Barcelona
Department of Internal Medicine
Hospital del Mar
P. Maritim 25-29
08002 Barcelona
Spain
V. Edusa
Department of Obstetrics, Gynecology and
Reproductive Sciences
Center for Research in Reproductive Biology
and
The Yale Center for Musculoskeletal Disorders
Yale University
333 Cedar St, FMB 331
New Haven, CT 06520
USA
B. Ettinger
Clinical Professor of Medicine
University of California
156 Lombard Street #13
San Francisco, CA
USA
A. Fadiel
Department of Obstetrics, Gynecology and
Reproductive Sciences
Center for Research in Reproductive Biology
and
The Yale Center for Musculoskeletal Disorders
Yale University
333 Cedar St, FMB 331
New Haven, CT 06520
USA
A. Falchetti
Department of Internal Medicine
University of Florence
Viale G. Pieraccini 6
50139 Florence
Italy
F. F erdeghini
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
M. Gambacciani
Department of Obstetrics and Gynecology
University of Pisa
Via Roma 67
56100 Pisa
Italy
E. Gazzerro
Department of Research
Saint Francis Hospital and Medical Center
Hartford, CT 06105
USA
and
The University of Connecticut School of
Medicine
Farmington, CT 06030
USA
x
https://t.me/med1917
LIST OF CONTRIBUTORS
H. K. Genant
Professor Emeritus
University of California
San Francisco
USA
and
Chairman, Board of Directors
Synarc, Inc
A. R. Genazzani
Department of Obstetrics and Gynecology
University of Pisa
Via Roma 67
56100 Pisa
Italy
L. Gennari
Department of Internal Medicine
Endocrine-Metabolic Sciences and Biochemistry
University of Siena
Viale Bracci 1
53100 Siena
Italy
D. Goltzman
Department of Medicine
McGill University
Montreal
Canada
J. Haapalahti
Orion Diagnostica R&D
Oulu
Finland
P. Hadji
Philipps University Marburg
Department of Gynecology and Obstetrics
Head of the Department of Endocrinology,
Osteoporosis and Reproductive Medicine
Pilgrimstein 3
35037 Marburg
Germany
J. Heikkinen
Deaconess Institute of Oulu
Oulu
Finland
K. Henriksen
Nordic Bioscience
Herlev Hovedgade 207
Herlev
Denmark
E. Horner
Chelsea and Westminster Hospital
London
UK
Y. Jiang
Osteoporosis and Arthritis Research Group
University of California
San Francisco
USA
J. A. Kanis
WHO Collaborating Centre for Metabolic Bone
Disease
University of Sheffield
Sheffield S10 2RX
UK
M. A. Karsdal
Nordic Bioscience
Herlev Hovedgade 207
Herlev
Denmark
J. S. Lee
Fellow in Endocrinology
Division of Endocrinology and Metabolism
University of California
156 Lombard Street #13
San Francisco, CA
USA
M. R. McClung
Oregon Osteoporosis Center
5050 NE Hoyt, Suite 651
Portland, OR 97213
USA
xi
https://t.me/med1917
POSTMENOPAUSAL OSTEOPOROSIS
C. Marcocci
Department of Endocrinology and Metabolism
University of Pisa
Via Paradisa 2
56124 Pisa
Italy
G. Martini
Department of Internal Medicine
Endocrine-Metabolic Sciences and Biochemistry
University of Siena
Viale Bracci 1
53100 Siena
Italy
D. Merlotti
Department of Internal Medicine
Endocrine-Metabolic Sciences and Biochemistry
University of Siena
Viale Bracci 1
53100 Siena
Italy
F. Naftolin
Department of Obstetrics, Gynecology and
Reproductive Sciences
Center for Research in Reproductive Biology
and
The Yale Center for Musculoskeletal Disorders
Yale University
333 Cedar St, FMB 331
New Haven, CT 06520
USA
R. E. Nappi
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
R. Nuti
Department of Internal Medicine
Endocrine-Metabolic Sciences and Biochemistry
University of Siena
Viale Bracci 1
53100 Siena
Italy
A. Ornati
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
S. Ortolani
Center for Metabolic Bone Disease
Istituto Auxologico Italiano
Divisione di Endocrinologia
Via Ariosto 13
20145 Milan
Italy
B. Pampaloni
Department of Internal Medicine
University of Florence
Viale G. Pieraccini 6
50139 Florence
Italy
S. E. Papapoulos
Department of Endocrinology & Metabolic
Diseases
Leiden University Medical Centre
Albinusdreef 2
2333 ZA Leiden
The Netherlands
R. C. Pereira
Department of Research
Saint Francis Hospital and Medical Center
Hartford, CT 06105
USA
A. Pinchera
Department of Endocrinology and Metabolism
University of Pisa
Via Paradisa 2
56124 Pisa
Italy
xii
https://t.me/med1917
LIST OF CONTRIBUTORS
F. Polatti
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
S. H. Ralston
Professor of Medicine and Bone Metabolism
University of Aberdeen Medical School
Institute of Medical Sciences
University of Aberdeen
Aberdeen AB25 2ZD
UK
D. M. Reid
Professor of Rheumatology
University of Aberdeen
Medical School
Foresterhill
Aberdeen AB25 2ZD
UK
R. Rizzoli
Division of Bone Diseases [WHO Collaborating
Center for Osteoporosis Prevention]
Department of Rehabilitation and Geriatrics
University Hospital of Geneva
CH 1211 Geneva 14
Switzerland
J. Ryan
Mapi Values Ltd
Adelphi Mill
Bollington
Cheshire SK10 5JB
UK
G. Saggese
Endocrine Unit
Division of Pediatrics
Department of Reproductive Medicine and
Pediatrics
University of Pisa
Pisa
Italy
N. A. Sims
St. Vincent’s Hospital
University of Melbourne
Melbourne
Victoria
Australia
A. Sommacal
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
J. Studd
Professor of Gynaecology
Chelsea and Westminster Hospital
London
UK
D. W. Sturdee
Department of Obstetrics and Gynaecology
Solihull Hospital
Solihull B91 2JL
UK
L. B. Tankó
Center for Clinical and Basic Research
Ballerup Byvej 222
Ballerup
Denmark
O. Tuncalp
Department of Obstetrics, Gynecology and
Reproductive Sciences
Center for Research in Reproductive Biology
and
The Yale Center for Musculoskeletal Disorders
Yale University
333 Cedar St, FMB 331
New Haven, CT 06520
USA
xiii
https://t.me/med1917
POSTMENOPAUSAL OSTEOPOROSIS
W. H. Utian
Gynecologist, The Cleveland Clinic
President Rapid Medical Research
Professor Emeritus, Case University, Cleveland,
Ohio
Executive Director, The North American
Menopause Society
5900 Landerbrook Drive, Suite 195
Mayfield Heights, OH 44124
USA
A. Verza
Department of Obstetrics and Gynecology
Policlinico S. Matteo
University of Pavia
Piazzale Golgi 2
27100 Pavia
Italy
E. Vignali
Department of Endocrinology and Metabolism
University of Pisa
Via Paradisa 2
56124 Pisa
Italy
J. Wactawski-Wende
Department of Social and Preventive Medicine
School of Public Health and Health Professions
University at Buffalo
Buffalo, NY 14221
USA
A. D. Woolf
Department of Rheumatology
Royal Cornwall Hospital
Peninsula Medical School
Universities of Exeter and Plymouth
Truro TR1 3LJ
UK
Y. Zöllner
Solvay Pharmaceuticals
Hans-Böckler-Allee 20
30173 Hannover
Germany
xiv
https://t.me/med1917
xv
The International Menopause Society (IMS) is a
society with a world-wide responsibility, and the
primary aim of the IMS is to support basic and
clinical research in climacteric medicine and, on
this basis, sustain global good medical practice.
Many questions have been raised in recent times
on menopause, hormone replacement and other
therapies. For these reasons, on behalf of the
IMS, we have organized workshops called ‘Con-
troversial Issues in Climacteric Medicine’, gath-
ering internationally recognized experts from all
around the world to discuss and debate with the
aim of elucidating the up-to-date consensus on
the management of specific issues of climacteric
medicine. Previous workshops have covered dif-
ferent issues regarding cardiovascular disease, the
brain, and cancer. Recently, in November 2004
in Pisa, we organized a workshop on post-
menopausal osteoporosis and the therapeutic
options.
Why osteoporosis? The reasons are epidem-
iological and pathophysiological: the vast majority
of subjects suffering form osteoporosis are post-
menopausal women, who develop the risk of
fragility fractures. Therefore, the IMS has to be
deeply involved in studies and investigations
regarding osteoporosis and to take the respon-
sibility to educate and inform about osteoporosis
diagnosis and treatment. The successful detection,
prevention and treatment of osteoporosis are a
rather recent challenge of modern medicine.
Estrogen deficiency plays a pivotal role in deter-
mining the etiology of the most common form of
osteoporosis: postmenopausal osteoporosis.
Established treatments are available, preventive
strategies are accessible. However, osteoporosis is
even now underdiagnosed and undertreated. In
our Workshop, different issues were covered,
from epidemiology to the controversies on meas-
urements of bone mineral density and their value
in diagnosing osteoporosis and in assessing the
risk of fracture. Concerning the issue of treat-
ment, the most relevant, hormone replacement,
and all the different options were covered and
carefully discussed.
We w o uld like this opportunity to express our
appreciation and gratitude to all the speakers
and moderators for their hard work in the long
days of our Workshop and their devoted efforts
in writing and reviewing the different chapters of
this book. Thanks to their hard work, we hope to
strengthen awareness in the medical community
and particularly among gynecologists, support-
ing the physicians in providing proper coun-
selling for the prevention of osteoporosis and
osteoporotic fractures, which currently severely
affect up to 40% of women over the age of 50
years.
A. R. Genazzani
Past President of the IMS
Preface
https://t.me/med1917
https://t.me/med1917
INTRODUCTION
Osteoporosis is currently defined as a skeletal
disorder characterized by compromised bone
strength predisposing a person to an increased
risk of fracture
1
. Bone strength primarily reflects
the integration of bone quality and bone density.
Bone quality refers to architecture, turnover,
damage accumulation and mineralization. Bone
density is expressed as grams of mineral per area
or volume, and in a given individual is deter-
mined by peak bone mass and amount of bone
loss. A fracture occurs when a failure-inducing
force such as trauma is applied to osteoporotic
bone. Thus, osteoporosis is a significant risk fac-
tor for fracture, and a distinction between risk
factors that affect bone metabolism and the risk
factors for fracture must be made.
Historically, osteoporosis and its sequelae
were recognized over 150 years ago, when it was
observed that hip fractures might result from an
age-related reduction in bone mass or quality.
However, the term osteoporosis entered medical
parlance in France and Germany in the 19th cen-
tury, where it was coined as a histological
description for aged human bone, emphasizing
the apparent porosity of the tissue. The histolog-
ical term subsequently evolved to discriminate
this condition from that of osteomalacia, and
came to mean bone present in reduced quantity,
with normal mineralization.
Osteoporosis has clinical and public-health
importance, and osteoporotic fractures are one of
the most common causes of disability and a
major contributor to medical-care costs in many
regions of the world. Indeed, for white women,
the one-in-six lifetime risk of sustaining a hip
fracture is greater than the one-in-nine risk of
developing breast cancer
2,3
. The social burden of
fractures will increase throughout the world as
the population ages. In this chapter we summa-
rize the epidemiology of osteoporosis and osteo-
porotic-related fractures and determine the
impact that this condition has on society.
Clinically, osteoporosis is recognized by the
occurrence of characteristic low-trauma frac-
tures, so that any clinically meaningful definition
of osteoporosis must include fracture. The main
advantage of a fracture-based definition is that
this is a discrete event that can be diagnosed
using a simple algorithm. The obvious disadvan-
tage with this definition is that diagnosis will be
exceptionally delayed in a disease where cur-
rently prevention is the optimum treatment.
This has led to present-day attempts to use bone
mass, as assessed by non-invasive densitometric
techniques, to predict future risk of fracture.
There is a well-established relationship
between bone mineral density (BMD) and the
ability of bone to withstand forces, such that
75–90% of the variance in bone strength is
related to BMD. Advances in medical technology
have developed highly accurate and reproducible
methods of measuring BMD, with minimal radi-
ation exposure, so that they are ideal for diagno-
sis and monitoring in osteoporosis. Using BMD,
prospective studies have shown that the risk of
osteoporotic fracture increases continuously and
progressively as BMD declines.
MAGNITUDE OF THE PROBLEM
How many people suffer from osteoporosis? It is
clear that the answer to this question will depend
on whether osteoporosis is defined on the basis of
Magnitude and impact of osteoporosis
and fractures
C. Marcocci, F. Cetani, E. Vignali and A. Pinchera
1
1
https://t.me/med1917
POSTMENOPAUSAL OSTEOPOROSIS
low bone mass or whether the emphasis, instead,
is on osteoporosis-related fractures.
Low bone mass is analogous to high blood
pressure in terms of its relationship to stroke, and
the risk of fracture increases when bone density
declines, just as the risk of stroke increases when
blood pressure rises. However, not all strokes
occur in hypertensive subjects, and fragility frac-
tures may occur in the absence of low bone mass,
although low bone mass is one of the most
strongly established risks of osteoporotic frac-
tures. Bone loss commonly occurs as men and
women age; however, an individual who does not
reach the peak of bone mass during childhood
and adolescence may develop osteoporosis with-
out the occurrence of accelerated bone loss.
Hence, suboptimal bone growth in childhood
and adolescence is as important as later bone loss
in the development of osteoporosis.
Currently, there is no accurate measure of
overall bone strength. Bone mineral density as
reported above is frequently used as a proxy
measure, and accounts for approximately 70% of
bone strength. An expert panel of the World
Health Organization (WHO) recently proposed
diagnostic criteria for osteoporosis based on bone
density, considering osteoporosis to be present
when BMD levels in white women are more than
2.5 standard deviations (SDs) below the young
normal mean
4
. Women with a history of one or
more fragility fractures are deemed to have severe
(‘established’) osteoporosis. Low bone mass
(‘osteopenia’) is defined by BMD levels more
than 1 SD below the young normal mean, but
less than 2.5 SD below. It is not clear how to
apply this diagnostic criterion to men and chil-
dren, or across ethnic groups. Because of the dif-
ficulty of accurate measurement and standardiza-
tion between instruments and sites, controversy
exists among experts regarding the continuous
use of this diagnostic criterion.
Most data on the prevalence of osteoporosis
derive from the Third National Health and
Nutrition Examination Survey (NHANES III), a
large sample of the United States population. As
assessed at the femoral neck, 20% of post-
menopausal white women have osteoporosis
5
.
No criteria for osteoporosis have been established
for non-white women, but 10% of Hispanic
women and 5% of African-American women
have femoral neck BMD values more than 2.5
SD below the young normal mean for white
women. Using the same cut-off value, osteoporo-
sis prevalence rates for white, Hispanic and
African-American men aged 50 years and over
are 4, 2 and 3%, respectively
5
. However, these
differences are related to overestimation of areal
BMD (g/cm
2
) in individuals with larger skele-
tons
6
. When bone size is taken into account, dif-
ferences in bone density between men and
women
7,8
and between women of difference races
are reduced
9–11
.
Osteoporosis is a systemic disease, and a
greater proportion of the population is seen to be
affected when more skeletal sites are assessed.
Most white women under the age of 50 years
have normal bone density, but, with advancing
age, the proportion with osteoporosis increases
dramatically. Among women aged 80 years and
over, for example, only 3% have normal bone
density at the hip, spine and forearm, while 27%
have osteopenia at one skeletal site or another,
and 70% have osteoporosis. As judged from
these data, about 54% of postmenopausal white
women in the United States have osteopenia and
another 30% have osteoporosis
12
.
The alternative approach to define the mag-
nitude of osteoporosis is to assess the frequency
of fragility fractures. There are no data regarding
the prevalence of distal forearm fracture. The
prevalence of hip fracture has been estimated at
5% for women at the age of 65 years and over
and at 0.6% for all ages
13
. Most available infor-
mation relates to vertebral fractures. In the Euro-
pean Vertebral Osteoporosis Study, 15 570
women and men were selected from population
registers in 36 European Centers and evaluated
according to a standardized protocol. The overall
prevalence of vertebral fracture depends upon
the method used for their evaluation. Using a
morphometric approach, the overall prevalence
of deformity was about 12% in both men and
women, but the increase in prevalence with age
was steeper among women. Thus, the frequency
of deformities in women aged 50–54 years was
5%, rising to 24% at age 75–79 years, while the
prevalence rose from 10% among men aged
50–54 years to 18% at age 75–79 years
14–17
.
2
https://t.me/med1917
MAGNITUDE AND IMPACT OF OSTEOPOROSIS AND FRACTURES
Using fracture incidence rates from the
United States, the estimated lifetime risk of a hip
fracture is 17% in white women and 6% in white
men
18,19
. This compares with risks of 16 and 5%
for clinically diagnosed vertebral fractures and 16
and 2% for distal forearm fractures in white
women and men, respectively. The lifetime risk
of any of the three fractures is 40% for women
and 13% for men from age 50 years onward
18
.
EPIDEMIOLOGY OF FRACTURES
Fracture incidence in the community is bimodal,
with peaks in youth and in the very elderly
2
. In
young people, fractures of the long bones pre-
dominate, often following substantial trauma,
and the incidence is greater in young men than
in young women. Above the age of 35 years,
overall incidence in women increases and the
female rates become twice those in men
20
. In the
United States, about 70% of all fractures in sub-
jects aged 45 years or over have been attributed
to osteoporosis. In this chapter, we concentrate
on fractures of the hip and spine because they
arise frequently and have been the most inten-
sively studied.
Hip fractures
Hip fractures are strongly related to low BMD,
and have become the international barometer of
osteoporosis, cause more disability and cost more
to repair than other types of osteoporotic frac-
ture. They are almost always treated in hospital,
and are therefore easier to count and compare
from country to country. Hip fracture incidence
rates increase exponentially with age in both
women and men in most regions of the world
21
.
This rise in fracture risk results from an age-
related decrease in BMD at the proximal femur,
as in vivo surrogate for bone fragility, and an age-
related increase in falls, which are responsible for
at least 90% of all hip fractures
22
.
The incidence of hip fracture differs between
populations. Thus, age-adjusted incidence rates
are higher among white women in Scandinavia
than in women of comparable age in North
America or Oceania
21
, whereas rates vary more
than seven-fold in European countries
23,24
. Simi-
lar variation is seen in the USA, with higher rates
recorded in the south-east than in the north or
west of the continent
25
. Rates of hip fracture are
also higher in urban than in rural areas of the
same country
26
, suggesting that factors related
to urbanization, such as decreased physical activ-
ity and conversion from softer ground to hard-
wood, tile, concrete and asphalt surfaces, could
contribute to an increased risk of hip fracture.
In the USA and Europe, the incidence of hip
fractures in women is twice that seen in men at
any age, because women have a lower BMD.
Furthermore, women live longer than men, and
hence more than three-quarters of all hip frac-
tures occur in women. Worldwide, the risk of hip
fracture varies more in women than in men, i.e.
the rates in men and women are similar in low-
risk populations, particularly those of Asian or
African heritage. This variation cannot be
explained by race-specific variation in bone den-
sity, and might be due to the larger bone size
with a greater mechanical strength
27
, a lower
risk of falling or other factors
28
. Important causes
of hip fracture in men are diseases associated
with secondary osteoporosis and falling
29
.
Like other complex chronic diseases, e.g.
osteoarthritis and atherosclerosis, the pathogene-
sis of hip fractures is multifactorial, and no single
factor (bone loss or falls) can completely account
for their occurrence. Thus, hip fractures are
strongly associated with BMD in the proximal
femur, but there are also many clinical predictors
of hip fracture risk that are independent of bone
density. A set of potential risk factors for hip frac-
ture was assessed in the Study of Osteoporotic
Fractures, a prospective study of 9516 white and
Asian-American women (Table 1). Hip fracture
incidence was 17 times greater among 15% of
the women who had five or more of the risk fac-
tors, exclusive of bone density, compared with
47% of the women who had two risk factors or
fewer. However, the women with five risk factors
had an even greater risk of hip fracture if their
bone density Z score was in the lowest tertile.
The majority of hip fractures in both sexes follow
a fall from standing height or less in individuals
with reduced bone strength
23
. Over a lifetime,
bone density at the femoral neck declines by an
3
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана