Cochrane Database Syst Rev. 2007 Jul
18;(3):CD004526.
WITHDRAWN: Calcium supplementation on bone loss in postmenopausal women.
Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, Hamel C, Ortiz Z, Peterson J, Adachi J, Tugwell P, Guyatt G; the Osteoporosis Methodology
Group; and the Osteoporosis Research
Advisory Group.
BACKGROUND: Although calcium
is one the simplest and least expensive strategies for preventing osteoporotic
fractures calcium supplementation is nevertheless not without controversy
(Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted
a bone health claim for calcium-rich foods, and the NIH in its Consensus
Development Process approved a statement that high calcium intake reduces the
risk of osteoporosis. OBJECTIVES: To assess the effects of calcium on bone
density and fractures in postmenopausal women. SEARCH STRATEGY: We searched
Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined
citations of relevant articles and proceedings of international meetings.
SELECTION CRITERIA: Trials that randomized postmenopausal women to calcium
supplementation or usual calcium intake in the diet and reported bone mineral
density of the total body, vertebral spine, hip, or forearm or recorded the
number of fractures, and followed patients for at least one year were considered
for inclusion. DATA COLLECTION AND ANALYSIS: Three independent reviewers
assessed the methodologic quality and extracted data for each trial. For each
bone density site (lumbar spine, total body, combined hip and combined
forearm), we calculated the weighted mean difference in bone density between
treatment and control groups using the percentage change from baseline. We
constructed regression models in which the independent variables were year and
dose, and the dependent variable was the effect size. This regression was used
to determine the years across which pooling was appropriate. Heterogeneity was
asssesed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS:
Fifteen trials, representing 1806 participants, were included. Calcium was more
effective than placebo in reducing rates of bone loss after two or more years
of treatment. The pooled difference in percentage change from baseline was
2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to
2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip,
and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of
fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk
for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). AUTHORS'
CONCLUSIONS: Calcium supplementation alone has a small positive effect on bone
density. The data show a trend toward reduction in vertebral fractures, but it
is unclear if calcium reduces the incidence of non vertebral fractures.
Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004523.
WITHDRAWN: Risedronate for the prevention and treatment of
postmenopausal osteoporosis.
Cranney A, Adachi J, Guyatt G, Papaioannou A, Robinson V, Shea B, Tugwell P, Waldegger L, Weaver B, Wells G, Zytaruk N.
BACKGROUND: Postmenopausal
osteoporosis results in an increased susceptibility to low-trauma fractures due
to reduced bone volume and microarchitectural deterioration. Risedronate, a
third generation bisphosphonate, has been shown in multiple clinical trials to
reduce fracture risk and improve bone mineral density in postmenopausal women
with osteoporosis. First and second generation bisphosphonates are known to
have gastrointestinal side-effects and risedronate may be better tolerated.
OBJECTIVES: To systematically review the efficacy of risedronate on bone
density, and fracture reduction in postmenopausal women. SEARCH STRATEGY: The
Cochrane Controlled Trials Registry Medline, and Current Contents were searched
from 1990 - 2001. The electronic search was supplemented by handsearching four
osteoporosis journals and their conference proceedings, as well as contacting
content experts and industry sources for unpublished data. SELECTION CRITERIA:
We included eight trials that randomised women to risedronate or an alternative
(placebo or calcium and /or vitamin D) and measured bone mineral density for at
least one year. DATA COLLECTION AND ANALYSIS: For each trial three independent
reviewers assessed the methodological quality and abstracted data. Data was
extracted for outcomes of fracture, bone mineral density and adverse events.
The more conservative random effects model was used to pool data. The quality
of trials was assessed according to the Jadad five-point scale. MAIN RESULTS:
Both vertebral and non-vertebral fractures were statistically and clinically
reduced with risedronate. Eleven out of one hundred women who received
risedronate had a vertebral fracture compared to 17 out of one hundred of those
who received calcium and vitamin D (pooled relative risk for vertebral
fractures of 0.64 (95% CI 0.52 - 0.77). Three percent of participants who
received risedronate had a non-vertebral fracture compared to 4.6% of those who
received calcium and vitamin D (pooled relative risk for nonvertebral fractures
of 0.73 (95% CI 0.61 - 0.87). The weighted mean difference for the percent
change from baseline for bone mineral density with 5 mg daily for lumbar spine,
femoral neck and trochanter was 4.54% (95%CI 4.12 - 4.97), p<0.01; 2.75%
(95% CI 2.32 - 3.17), p<0.01; and 4.38% (95% CI 3.51 - 5.25), p<0.01
respectively. AUTHORS' CONCLUSIONS: There is good evidence for the efficacy of
risedronate in the reduction of both vertebral and non-vertebral fractures. In
addition, there is evidence from randomized trials that risedronate is able to
achieve this without increasing risk for overall withdrawals due to adverse
effects.
Obesity (Silver Spring). 2007
Jul;15(7):1827-1840.
Morbidity and Mortality Risk Associated With an Overweight BMI in Older
Men and Women.
School of Kinesiology and
Health Studies, Queen’s University,
Background: There is
controversy as to whether older adults with a BMI in the overweight range (25
to 29.9 kg/m(2)) are at increased health risk and whether they should be
encouraged to lose weight. The purpose of this study was to determine whether
older adults with a BMI in the overweight range are at increased morbidity and
mortality risk. Methods: Participants consisted of 4968 older (>/=65 years)
men and women from the Cardiovascular Health Study limited access dataset.
Based on BMI (kg/m(2)), participants were grouped into normal-weight (20 to
24.9 kg/m(2)), overweight (25 to 29.9 kg/m(2)), and obese (>/=30 kg/m(2))
categories. Participants were followed for up to 9 years to determine if they
developed 10 weight-related health outcomes that are pertinent to older adults.
Cox proportional hazards models were used to estimate the hazards ratios of
morbidity and mortality after adjusting for age, sex, income, smoking, and
physical activity. RESULTS: Compared with the normal-weight group, the risks of
myocardial infarction, stroke, sleep apnea, urinary incontinence, cancer, and
osteoporosis were not different in the overweight group (p > 0.05). The
risks for arthritis and physical disability were modestly increased in the
overweight group (p < 0.05), whereas the risk for type 2 diabetes was
increased by 78% in the overweight group (p < 0.01). After adjusting for all
relevant covariates, all-cause mortality risk was 11% lower in the overweight
group (p < 0.05). Conclusions: A BMI in the overweight range was associated
with some modest disease risks but a slightly lower overall mortality rate.
These findings suggest that a BMI cut-off point of 25 kg/m(2) may be overly
restrictive for the elderly.
Curr Med Res Opin. 2007 Jul 12; [Epub
ahead of print]
Prevalence of vitamin D inadequacy in European postmenopausal women.
OBJECTIVE: Inadequate vitamin
D level is associated with secondary hyperparathyroidism and increased bone
turnover and bone loss, which in turn increases fracture risk. The objective of
this study is to assess the prevalence of inadequate serum vitamin D levels in
postmenopausal European women. There are no clear international agreements on
what constitutes a level of vitamin D inadequacy, but recent publications
suggest that the circulating level of vitamin D should be over 80 nmol/L or at
least between 50 and 80 nmol/L.MATERIAL AND METHODS: Assessment of
25-hydroxyvitamin D [25(OH)D] was performed in 8532 European postmenopausal
women with osteoporosis or osteopenia. European countries included
Osteoporos Int. 2007 Jul 19; [Epub
ahead of print]
Effectiveness of antiresorptive agents in the prevention of recurrent
hip fractures.
Morin S, Rahme E, Behlouli H, Tenenhouse A, Goltzman D, Pilote L.
Division of Internal Medicine,
McGill University Health Center (MUHC), 1650 Cedar Ave, Room B2-118, Montreal,
QC, H3G 1A4, Canada.
Hip fracture is associated
with recurrent fractures and increased mortality. The results of our
retrospective cohort study support the use of antiresorptive agents to prevent
recurrent hip fractures in this population. INTRODUCTION: Hip fracture, the
most serious consequence of osteoporosis, is associated with recurrent
fractures and increased mortality. Antiresorptive therapy has proven efficacy in
the prevention of fractures after vertebral fractures. It is unknown if it can
prevent recurrent fractures after a hip fracture. METHODS: We designed a
population based, retrospective cohort study, using administrative databases
and identified patients hospitalized for a hip fracture between 1996 and 2002.
The exposure was defined as being dispensed a prescription for an
antiresorptive agent at any time following discharge. Multivariate Cox
regression models were used to estimate the hazard ratio of recurrent hip
fracture. Subgroup and propensity score analyses were performed. RESULTS: A
total of 20,644 patients were identified; 6,779 filled a prescription for
antiresorptive agents. There were 992 recurrent hip fractures. Patients exposed
to antiresorptives had a 26% reduction in the rate of recurrent fractures
(adjusted hazard ratio 0.74; 95% CI, 0.64-0.86) compared to patients who were
not. All subgroups experienced a reduction in recurrent fracture, except the
very elderly. Propensity score analyses were consistent with the main analysis.
CONCLUSIONS: Antiresorptive therapy reduces the risk of recurrent hip fractures
in elderly patients. These results provide evidence that this therapy should be
considered for secondary prevention of hip fractures.
Endocr J. 2007 Jul 20; [Epub ahead of print]
Subclinical Hypothyroidism is Related to Lower Heel QUS in
Postmenopausal Women.
Nagata M, Suzuki A, Sekiguchi S, Ono Y, Nishiwaki-Yasuda K, Itoi T, Yamamoto S, Imamura S, Katoh T, Hayakawa N, Oda N, Hashimoto S, Itoh M.
Division of Endocrinology and
Metabolism, Department of Internal Medicine,
Recent findings suggest that
thyroid stimulating hormone (TSH) is a negative regulator of skeletal
remodeling by reducing both differentiation of osteoblasts and formation of
osteoclasts. In addition, increased fracture risk in untreated hypothyroid
patients has been reported to begin up to 8 years before diagnosis. The aim of
the present study was to evaluate the effect of subclinical hypothyroidism on
bone structure by using the heel QUS. Subjects were outpatients without any
past or present history of thyroid disease. Among 210 postmenopausal women, 22
of 33 patients (Hypo), who had elevated serum TSH concentration (TSH >/=4
muU/ml) with normal serum free thyroxine (FT(4)) concentration, agreed to join
to this study. We also randomly selected 24 control subjects (Cont) from 176
postmenopausal women with normal thyroid status. Calcaneus osteo sono
assessment indices (OSI) of right feet were measured using the ultrasound bone
densitometry AOS-100. Serum TSH concentrations in Hypo patients (5.31 +/- 1.3
muU/ml) were higher than those in Cont patients (2.05 +/- 1.1 muU/ml), and
there was significant difference of FT(4) concentrations (Cont 1.33 +/- 0.15
ng/dl; Hypo 1.19 +/- 0.17 ng/dl). OSI and its Z-score in Hypo subjects (OSI,
2.138 +/- 0.152; Z-Score -0.322 +/- 0.504 SD, Mean +/- SD) were significantly
lower than those in Cont subjects (OSI, 2.347 +/- 0.243; Z-Score 0.322 +/- 0.91
SD, Mean +/- SD). Simple regression statistical analysis showed that OSI
decreased according to the increase of serum TSH concentration (n = 47,
P<0.037). In addition, multiple regression analysis showed that the
elevation of serum TSH concentration was associated with the decrease of OSI.
These results suggest that the elevation of serum TSH concentration in
subclinical hypothyroidism affects not bone turnover but bone structure as
assessed by QUS.
Nutr Cancer. 2007;58(2):136-45.
Lifestyle and Dietary Correlates of Plasma Insulin-Like Growth Factor
Binding Protein-1 (IGFBP-1), Leptin, and C-Peptide: The Multiethnic Cohort.
Henderson KD, Rinaldi S, Kaaks R, Kolonel L, Henderson B, Le Marchand L.
Circulating insulin-like
growth factor binding protein 1 (IGFBP-1), leptin, and insulin are 3 proteins
modified by obesity and have been associated with cancer at several sites in
past studies. We conducted a cross-sectional study to describe the correlation
of these proteins with gender, race/ethnicity, anthropometric indexes, and dietary
and lifestyle factors. We measured fasting plasma levels of IGFBP-1, leptin,
and C-peptide, used here as a stable measure of insulin secretion, in a random
sample of 450 male and 352 postmenopausal female Hawaii and Los Angeles
Multiethnic Cohort Study (MEC) participants (age range 47-82 yr at blood draw).
Through a series of multiple linear regressions, we found that the most
parsimonious model for plasma IGFBP-1 included inverse associations with age,
body mass index (BMI), and regular soda intake. A term for interaction between
age and BMI was positively associated with plasma IGFBP-1. Adjusted mean plasma
leptins were highest among Whites and African Americans and lowest among
Hawaiians and Japanese Leptin was also inversely associated with age and positively
associated with the interaction between age and race/ethnicity, female gender,
and BMI. A model with only race/ethnicity and BMI (positive association) was
best for plasma C-peptide. Adjusted means for C-peptide were highest for
Japanese and Whites and lowest for African Americans. The overall percent of
variance in protein levels explained by these models was low for
IGFBP-1(R2=0.17) and C-peptide (R(3)=0.11) and higher for leptin (R(2)=0.57).
We saw no clear correlation between racial/ethnic trends in protein levels with
those of colorectal, breast, or prostate cancer incidence rates in the MEC.
Research to clarify factors associated with determination of these proteins and
their relationship with cancer etiology is warranted.
Nutr Cancer. 2007;58(2):127-35.
Dietary fiber intake and endogenous serum hormone levels in naturally
postmenopausal mexican american women: the multiethnic cohort study.
Monroe KR, Murphy SP, Henderson BE, Kolonel LN, Stanczyk FZ, Adlercreutz H, Pike MC.
Department of Preventive
Medicine,
This study investigated
dietary fiber intake in association with serum estrogen levels in naturally
postmenopausal
Endocr Relat Cancer. 2007
Jun;14(2):169-87.
Critical assessment of new risk factors for breast cancer:
considerations for development of an improved risk prediction model.
Santen RJ, Boyd NF, Chlebowski RT, Cummings S, Cuzick J, Dowsett M, Easton D, Forbes JF, Key T, Hankinson SE, Howell A, Ingle J.
Internal
Medicine/Endocrinology,
The majority of candidates for
breast cancer prevention have not accepted tamoxifen because of the perception
of an unfavorable risk/benefit ratio and the acceptance of raloxifene remains
to be determined. One means of improving this ratio is to identify women at
very high risk of breast cancer. Family history, age, atypia in a benign
biopsy, and reproductive factors are the main parameters currently used to
determine risk. The most powerful risk factor, mammographic density, is not
presently employed routinely. Other potentially important factors are plasma
estrogen and androgen levels, bone density, weight gain, age of menopause, and
fracture history, which are also not currently used in a comprehensive risk
prediction model because of lack of prospective validation. The Breast Cancer
Prevention Collaborative Group (BCPCG) met to critically examine and prioritize
risk factors that might be selected for further testing by multivariate
analysis using existing clinical material. The BCPCG reached a consensus that
quantitative breast density, state of the art plasma estrogen and androgen
measurements, history of fracture and height loss, BMI, and waist-hip ratio had
sufficient priority for further testing. As a practical approach, these
parameters could be added to the existing Tyrer-Cuzick model which encompasses
factors included in both the Claus and Gail models. The BCPCG analyzed
potentially available clinical material from previous prospective studies and
determined that a large case/control study to evaluate these new factors might
be feasible at this time.
Cancer Causes Control. 2007 Jul 19; [Epub
ahead of print]
Breast density in relation to risk of ductal carcinoma in situ of the
breast in women undergoing screening mammography.
Mackenzie TA, Titus-Ernstoff L, Vacek PM, Geller B, Weiss JE, Goodrich ME, Carney PA.
Department of Community &
Family Medicine, Dartmouth Medical School, Norris Cotton Cancer Center,
Hanover, NH, USA.
OBJECTIVE: To examine the
association between breast density and risk of breast ductal carcinoma in situ
(DCIS). METHODS: We assessed breast density in relation to DCIS risk using
combined data from statewide mammography registries in NH and VT. The
prospective analyses were based on 572 DCIS cases arising in 154,936 women
(58,496 premenopausal and 96,440 postmenopausal). Women in the study were
followed on average 4.1 years. Breast density was scored by community
radiologists using BIRADS categories (fatty, scattered density, heterogeneous
density, extreme density). RESULTS: In premenopausal women, based on 157 cases,
the RR for DCIS risk were 0.29 (95% CI: 0.0.04, 2.24) for fatty breasts, 2.06
(95% CI: 1.39, 3.05) for heterogeneous density, and 2.40 (95% CI: 1.47, 3.91)
for extreme density, relative to scattered density. In postmenopausal women,
based on 369 cases, the RR for DCIS risk were 0.58 (95% CI: 0.37, 0.93) for
fatty breasts, 1.41 (95% CI: 1.12, 1.78) for heterogeneous density, and 1.49
(95% CI: 0.93, 2.37) for extreme density, relative to scattered density. The
possible interaction between breast density and menopausal status in relation
to DCIS risk was not statistically significant. CONCLUSIONS: We observed an
association between breast density and DCIS risk. Although the association
seemed stronger in premenopausal women, there was no evidence of an interaction
involving breast density and menopausal status.
BMJ. 2007 Jul 11; [Epub
ahead of print
Main morbidities recorded in the women's international study of long
duration oestrogen after menopause (WISDOM): a randomised controlled trial of
hormone replacement therapy in postmenopausal women.
Vickers MR, Maclennan AH, Lawton B, Ford D, Martin J, Meredith SK, Destavola BL, Rose S, Dowell A, Wilkes HC, Darbyshire JH, Meade TW.
MRC General Practice Research
Framework, Stephenson House,
OBJECTIVE: To assess the long
term risks and benefits of hormone replacement therapy (combined hormone
therapy versus placebo, and oestrogen alone versus combined hormone therapy).
DESIGN: Multicentre, randomised, placebo controlled, double blind trial.
SETTING: General practices in
J
Sex Med. 2007
Jul;4(4i):1001-1008
Evaluation of the Clinical Relevance of Benefits Associated with
Transdermal Testosterone Treatment in Postmenopausal Women with Hypoactive
Sexual Desire Disorder.
Kingsberg S, Shifren J, Wekselman K, Rodenberg C, Koochaki P, Derogatis L.
University Hospitals of
Cleveland,
Introduction. Postmenopausal
women with hypoactive sexual desire disorder (HSDD) experienced statistically
significant improvements in the frequency of satisfying sexual activity, sexual
desire, and distress with testosterone treatment in phase III trials, but it
was not known whether the magnitude of these effects was clinically meaningful.
The clinical relevance study was designed to answer this question. Aim. To
evaluate the clinical relevance of the treatment benefits. Methods. This study
involved a representative sample of 132 surgically postmenopausal women with
HSDD who were enrolled in two randomized, placebo-controlled trials (N = 1094)
assessing the efficacy and safety of transdermal testosterone treatment (300
mcg/day) for 6 months. At the end of the studies, prior to unblinding, a sample
of women (12%) was interviewed concerning their experiences with the treatment.
Main Outcome Measures. Women were asked "Overall, would you say that you
experienced a meaningful benefit from the study patches?" Changes in the
efficacy end points in the double-blind studies were compared for the women who
did and did not experience an overall meaningful benefit. Results. Overall, 33
of 64 women (52%) who received testosterone reported experiencing a meaningful
treatment benefit, compared with 21 of 68 women (31%) who received placebo (P =
0.025). Among the women who identified themselves as experiencing a meaningful
benefit, the mean (SE) change from baseline in 4-week frequency of satisfying
sexual activity was 4.4 (0.76), in desire score was 21.0 (2.78), moving from
"seldom" to "sometimes" feeling sexual desire, and in
distress score was -36.5 (3.96), moving from "often" to
"seldom" being distressed. Among the women who identified themselves
as not experiencing a meaningful benefit, the mean (SE) change from baseline in
4-week frequency of satisfying sexual activity was 0.5 (0.31), in desire score
was 2.9 (1.42), and in distress score was -8.8 (2.23). Conclusions. Surgically
menopausal women with HSDD in these studies received clinically meaningful
benefits, including improvements in satisfying sexual activity, sexual desire,
and personal distress.
J
Sex Med. 2007
Jul;4(4i):1056-1069
The Burden of Testosterone Deficiency Syndrome in Adult Men: Economic
and Quality-of-Life Impact.
Maggi M, Schulman C, Quinton R, Langham S, Uhl-Hochgraeber K.
Andrology Unit, Department of
Clinical Physiopathology,
Introduction. Testosterone
deficiency syndrome (TDS) causes a wide range of symptoms that can lead to
significant morbidity. Preliminary evidence has also linked TDS with premature
mortality and with a number of comorbid diseases including diabetes and
metabolic syndrome. Such associations can lead to substantial economic and
quality- of-life implications, the magnitude of which remains largely unknown.
Aim. To review the economic and quality-of-life consequences of a largely
untreated condition and to consider the likely health economic benefits of
testosterone treatment. Methods. A systematic review of four main areas:
epidemiological evidence of the magnitude of TDS, estimates of cost of illness,
impact on quality-of-life, and cost-effectiveness of testosterone treatment.
Main Outcome Measure. Review of peer-reviewed literature. Results. The lack of
clear universally accepted diagnostic criteria and the uncertainty surrounding
the link between TDS and some of its consequences complicate the estimation of
the burden of illness of TDS. Consequences of TDS that potentially lead to
increased economic burden include depression, sexual dysfunction, mild
cognitive impairment, osteoporosis, cardiovascular disease, and mortality.
However, although good evidence exists demonstrating an association between TDS
and sexual dysfunction and cognitive impairment, evidence is less strong for
depression, the incidence of fractures and mortality, and highly controversial
for cardiovascular disease. The consequences that are likely to impact on
patients' quality of life include sexual function, energy levels, body
composition, mood, and cognitive function. Conclusion. Understanding the burden
is only the first step decision makers need to take to decide whether to
allocate scarce resources to treat the condition. To make informed decisions on
when and who to treat information is also needed on the cost-effectiveness of
available treatments. Such data would highlight the benefits of treatment of
TDS to physicians, patients, and to society as a whole.
Aust N Z J Obstet Gynaecol. 2007 Aug;47(4):329-34
A quantitative analysis of the menopause experience of Indian women
living in
School of Public Health and
Community Medicine, Faculty of Medicine, The University of New South Wales,
Sydney, New South Wales, Australia.
Aims: To examine the
experience of menopause in Indian women (aged 45-65 years) in
Menopause. 2007 Jul
6; [Epub ahead of print
Association of general and abdominal obesities and metabolic syndrome
with subclinical atherosclerosis in asymptomatic Chinese postmenopausal women.
Yu RH, Ho SC, Ho SS, Woo JL, Ahuja AT.
From the 1Department of
Community and Family Medicine, Chinese University of Hong Kong, School of
Public Health; 2Department of Diagnostic Radiology and Organ Imaging, the
Chinese University of Hong Kong, The Sir Yue-kong Pao Centre for Cancer, and
the Lady Pao Children's Cancer Centre; and 3Department of Medicine and
Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital,
Shatin, N.T., Hong Kong, SAR.
OBJECTIVE:: This study aimed
to investigate the relationships between obesity, especially abdominal obesity,
andmetabolic syndrome (MS) with carotid intima-media thickness (IMT) and
plaque, markers of subclinical atherosclerosis, in asymptomatic Chinese
postmenopausal women in
J Musculoskelet Neuronal Interact. 2007 Apr-Jun;7(2):144-8.
Common musculoskeletal adverse effects of oral treatment with once
weekly alendronate and risedronate in patients with osteoporosis and ways for
their prevention.
Bock O, Boerst H, Thomasius FE, Degner C, Stephan-Oelkers M, Valentine SM, Felsenberg D.
Centre for Muscle and Bone
Research, Charite - University Medicine
Objective: To examine in a
major cohort of patients whether or not musculoskeletal adverse effects (MAEs),
similar to those seen in intravenous bisphosphonates (BP), might occur also in
high dosage oral treatment regimens with alendronate (ALN) and risedronate
(RSN). Patients and methods: 612 consecutive patients treated in the
osteoporosis outpatient clinic at Charite, Campus Benjamin Franklin, between
July 2002 and October 2003 with oral ALN or RSN (mean age 68.2+/-9.7 years; 527
females, 85 males), were examined and followed up for MAEs. Results: The overall
frequency of any severe MAEs in our patients was low (5.6%). All severe MAEs
occurred in primarily once weekly treated patients: 27 in ALN 70 mg once weekly
(27/134=20.1%) and 7 in RSN 35 mg once weekly (7/28=25.0%), with no significant
difference between those groups. The most frequently reported MAE was acute
arthralgia in 12.6%, followed by acute back pain in 9.1% of all primarily once
weekly treated cases. None of the 302 patients initially treated with daily BP
reported any MAEs when later switching to once weekly administration (218
patients to ALN 70 mg once weekly and 84 patients to RSN 35 mg once weekly).
With reference to recently published data, the phenomenon is probably related
to dose dependent gammadelta T cell activation by accumulation of isopentenyl
pyrophosphate (IPP) due to inhibition of the mevalonate pathway by nitrogen
containing bisphosphonates (nBP). Conclusions: MAEs in oral BP are, in general,
less common and severe than in intravenous BP. They are observed exclusively in
patients starting ALN or RSN treatment with once weekly dosage regimens. In
order to avoid this phenomenon, it is suggested to start ALN or RSN treatment
with the lower daily dosages of ALN 10 mg daily or RSN 5 mg daily for about two
weeks before switching to the overall, more convenient, once weekly dose
regimen.
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1443-8. Epub 2007 Jul
Dietary patterns and breast cancer risk in the shanghai breast cancer
study.
Cui X, Dai Q, Tseng M, Shu XO, Gao YT, Zheng W.
The association of breast
cancer with dietary patterns such as a western diet has not been studied in
Asian women. We examined this among Shanghai Breast Cancer Study participants.
Cases were of ages 25 to 64 years, diagnosed 08/1996-03/1998, and identified
through a rapid case ascertainment system supplemented by the Shanghai Cancer
Registry. Controls, selected from the general population of urban
BMC Public Health. 2007 Jul 9;7(1):150
[Epub ahead of print
Changes in body mass index in Canadians over a five-year period: Results
of a prospective, population-based study.
Hopman WM, Leroux C, Berger C, Joseph L, Barr SI, Prior JC, Harrison M, Poliquin S, Towheed T, Anastassiades T, Goltzman D, Research Group C.
ABSTRACT: Background The
initiation of the Canadian Multicentre Osteoporosis Study in 1996, and
subsequent follow-up of the cohort 5 years later, provided longitudinal body
mass index (BMI) data for a random sample of Canadians. Methods Height and
weight were measured at baseline and 5 years and used to calculate BMI and
assign one of six weight categories. Multiple imputation was used to adjust for
missing weight at year 5. Data were stratified by age and gender. The
proportion of participants moving between categories was generated, and
multivariable linear regression was used to identify factors associated with
weight change. Results Baseline data were available for 8548 participants, year
5 data for 6721, and year 5 weight was imputed for 1827 (17.6%). Mean BMI for
every age and gender group exceeded healthy weight guidelines. Most remained
within their BMI classification over 5 years, but when change occurred, BMI
category was more likely to increase than decrease. Several sociodemographic,
lifestyle and clinical characteristics were associated with change. Conclusions
Mean baseline BMI tended to be higher than recommended. Moreover, on average,
men under age 45 and women under age 55 were gaining approximately 0.45
kilograms (one pound) per year, which leveled off with increased age and
reversed in the oldest age groups. These findings underscore the need for
public health efforts aimed at combating obesity.
BMC Public Health. 2007 Jul 7;7(1):149 [Epub ahead of print
Early menopause, association with tobacco smoking, coffee consumption
and other lifestyle factors: a cross-sectional study.
Mikkelsen TF, Graff-Iversen S, Sundby J, Bjertness E.
ABSTRACT: BACKGROUND: Early
onset of menopause is a risk factor for several health problems. The objective
was primarily to investigate the association between early menopause and
current, past active and passive smoking. A second aim was to investigate the
association between coffee and alcohol consumption and early menopause.
METHODS: The present population-based cross-sectional study included a
sub-sample of 2123 postmenopausal women born in 1940-41 who participated in the
Oslo Health Study. Early menopause was defined as menopause occurring at an age
of less than 45 years. We applied logistic regression analyses (crude and
adjusted odds ratio (OR)) to examine the association between early menopause
and selected lifestyle factors. RESULTS: Current smoking was significantly
associated with early menopause (adj. OR, 1.59; 95% CI, 1.11-2.28). Stopping
smoking more than 10 years before menopause considerably reduced the risk of
early menopause (adj. OR, 0.13; 95% CI, 0.05-0.33). Total exposure to smoking
(the product of number of cigarettes per day and time as a smoker) was
positively related to early menopause and, at the highest doses, nearly doubled
the odds (adj. OR, 1.93; 95% CI, 1.12-3.30). These data suggest a possible
dose-response relationship between total exposure to smoking and early
menopause, but no dose-response relationship was detected for the other
variables examined. We found no significant association of coffee or alcohol
consumption with early menopause. Of the lifestyle factors tested, high
educational level (adj. OR, 0.50; 95% CI, 0.34-0.72) and high social
participation (adj. OR, 0.60, 95% CI, 0.39-0.98) were negatively associated
with early menopause. CONCLUSIONS: This cross-sectional study shows an
association between current smoking and early menopause. The data also suggest
that the earlier a woman stops smoking the more protected she is from early
menopause. Early menopause was not significantly associated with passive
smoking, or alcohol or coffee consumption.
J
Sex Med. 2007 Jul;4(4i):859-866
Management of Female Sexual Dysfunction in Postmenopausal Women by
Testosterone Administration: Safety Issues and Controversies.
Department of Medicine,
Introduction. A Food and Drug
Administration advisory group has questioned the long-term safety of
testosterone administration to postmenopausal women. Although only short-term
data exist on safety from the double-blind, placebo-controlled trials,
testosterone has been used for more than 50 years. Therefore, some data
concerning the long-term safety issues must exist in the literature. Aim. To
review the published data concerning the safety of administration of testosterone
to women. Methods. Review of published articles identified by a search of the
Ovid databases and bibliographies from articles identified as dealing with the
topics of testosterone or androgen treatment of women. Results. The major
adverse reactions to exogenous androgens are the expected androgenic side
effects of hirsutism and acne. High-density lipoprotein levels may be decreased
with oral androgens. There are insufficient long-term safety data regarding
breast, endometrium, or heart safety to draw strong conclusions, although the
data available to date are reassuring. Conclusions. Testosterone administration
to postmenopausal women that result in physiological to slightly
supraphysiological serum-free testosterone levels is safe for at least 2 years.
Neurobiol Aging. 2007 Jun 29; [Epub
ahead of print]
Menopausal transition: A possible risk factor for brain pathologic
events.
Bonomo SM, Rigamonti AE, Giunta M, Galimberti D, Guaita A, Gagliano MG, Müller EE, Cella SG.
Department of Medical
Pharmacology, University of Milan, Fondazione IRCCS Ospedale Maggiore
Policlinico, Milan, Italy; Center of Excellence for Neurodegenerative Diseases
(CEND), University of Milan, Italy.
BACKGROUND AND OBJECTIVE:
Incidence and prevalence of Alzheimer's disease (AD) are higher in
postmenopausal women than in age-matched men. Since at menopause the endocrine
system and other biological paradigms undergo substantial changes, we thought
to be of interest studying whether (and how) the balance between some
biological parameters allegedly neuroprotective (e.g. related to estrogen,
dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic
(e.g. related to glucocorticoid and interleukin-6 activities) vary during
lifespan in either sex in either normalcy or neurodegenerative disorders.
SUBJECTS AND METHODS: Along with this aim, we evaluated the gene expression
levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs),
interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly
playing a key role in the proinflammatory events associated with AD, in a
population of 209 healthy subjects (73M, 106F, 20-91-year old) and 85 AD
patients (36M, 49F, 65-89-year old). Results obtained were related to plasma
titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS).
Studies were performed in peripheral leukocytes, since these cells (1) are
easily obtainable by a simple blood sampling, (2) express many molecules and
multiple receptors which are under the same regulatory mechanisms as those
operative in the brain and (3) some of them, e.g. monocytes, share many
functions with microglial cells. RESULTS: In healthy men all the study
parameters were quite stable during lifespan. In women, instead, at menopausal
transition, some changes that may predispose to neurodegeneration occurred. In
particular, there was (1) an up-regulation of ERs, and a concomitant increase
of IL-6 gene expression, events likely due to the loss of the inhibitory
control exerted by estradiol (E(2)); (2) an increase of HGRalpha:HGRbeta ratio,
indicative of an augmented cortisol activity on HGRalpha not sufficiently
counteracted by the inhibitory HGRbeta function; (3) a reduced CD36 expression,
directly related to the increased cortisol activity; and (4) an augmented
plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic
index for the risk of neurodegeneration. In AD patients of both sexes, the
expression of the study parameters was similar to that found in sex- and
age-matched healthy subjects, thus indicating their unrelatedness to the
disease, and rather a better correlation with biological events. CONCLUSIONS:
Menopausal transition is a critical phase of women's life where the occurrence
of an unfavorable biological milieu would predispose to an increased risk of
neurodegeneration. Collectively, the higher prevalence of AD in the female
population would depend, at least in part, on the presence of favoring
biological risk factors, whose contribution to the development of the disease
occurs only in the presence of possible age-dependent triggers, such as
beta-amyloid deposition.
Calcif Tissue Int. 2007 Jul 6; [Epub
ahead of print]
Evidence that Treatment with Risedronate in Women with Postmenopausal
Osteoporosis Affects Bone Mineralization and Bone Volume.
Fratzl P, Roschger P, Fratzl-Zelman N, Paschalis EP, Phipps R, Klaushofer K.
Department of Biomaterials,
Max Planck Institute of Colloids and Interfaces,
Risedronate is used in osteoporosis
treatment. Postmenopausal women enrolled in the Vertebral Efficacy with
Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for
3 years. Subjects received calcium and vitamin D supplementation if deficient
at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline
and at 3 years. Quantitative back-scattered electron imaging (qBEI) was
performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13)
before and after treatment, and the mineral volume fraction in the trabecular
bone was calculated. Combining dual-energy X-ray absorptiometric values with
the mineral volume fraction for the same patients allowed us to calculate the
relative change in trabecular bone volume with treatment. This showed that the
effect on BMD was likely to be due partly to changes in matrix mineralization
and partly due to changes in bone volume. After treatment, trabecular bone
volume in the lumbar spine tended to increase in the risedronate group (+2.4%,
nonsignificant) but there was a significant decrease (-3.7%, P < 0.05) in
the placebo group. Calcium supplementation with adequate levels of vitamin D
led to an approximately 3.3% increase in mineral content in the bone material
independently of risedronate treatment. This increase was larger in patients
with lower matrix mineralization at baseline and likely resulted from
correction of calcium/vitamin D deficiency as well as from reduced bone
remodeling. Combining BMD and bone mineralization density distribution data show
that in postmenopausal osteoporosis 3-year treatment with risedronate preserves
or may increase trabecular bone volume, unlike placebo. This analysis also
allows, for the first time, separation of the contributions of bone volume and
matrix mineralization to the increase in BMD.
Nutr Hosp. 2007 May-Jun;22(3):313-21.
Dietary food habits, nutritional status and lifestyle in menopausal
women in Spain
Ubeda N, Basagoiti M, Alonso-Aperte E, Varela-Moreiras G.
Dpto Nutrición, Bromatología y Tecnología de los Alimento, Fac.
Farmacia, Universidad CEU San Pablo, Madrid.
AIM: To analyse the diet and
the dietary food habits in a sample of 1,218 Spanish women, aged 40 to 77
years, in the menopausal or perimenopausal condition. Women were recruited
nationwide and the diet was assessed using a food frequency questionnaire.
RESULTS: Diet in our population group was close to the representative dietary
habits of the Spanish population, except for dairy products. These were highly
consumed (approximately 4 servings/day) by menopausal women. Energy, protein
and cholesterol intakes, as well as most vitamins and mineral intakes, were
very high, as compared to recommended dietary allowances. We only found
marginal deficient intakes for folate and vitamin D. Women over 60 years
consume less eggs, sweats, sugar and miscellany, and therefore less lipids and
cholesterol, as well as vitamin D, than younger women. A high rate (61%) of
overweight and obesity (BMI > 25) was present in our population group and
was associated with a higher intake of meat, fish and eggs, as well as energy.
A healthier diet (high intake of dairy products, fresh vegetables, fruits,
legumes, cereals and fish) was associated with a healthier lifestyle (no
smoking, physical exercise) and the use of fortified foods and vitamin/mineral
supplements. A high percentage of women regularly consumed fortified food
(52,7%) and micronutrient supplements (22,8%) although diets provided enough
vitamins and minerals. CONCLUSION: Diet in our study group is in accordance to
healthy dietary habits and physical activity recommendations. This is probably
due to a greater concern for health in women close to the menopause condition.
Int J Oncol. 2007 Aug;31(2):303-12.
Immune-surveillance and programmed cell death-related genes are
significantly overexpressed in the normal breast epithelium of postmenopausal
parous women.
Balogh GA, Russo IH, Spittle C, Heulings R, Russo J.
Breast Cancer Research
Laboratory,
Endocrine and reproductive
influences significantly affect the lifetime risk of breast cancer. Nulliparity
is one of the most firmly established risk factors for breast cancer, whereas
early full-term pregnancy and parity confer a significant protection. The
breast attains its maximum development during pregnancy and lactation. After
menopause the breast regresses in both nulliparous and parous women containing
lobular structures designated lobules type 1 (Lob 1). We have postulated that
the degree of differentiation acquired through early pregnancy changes the
'genomic signature' that differentiates the Lob 1 from the early parous women
from that of the nulliparous women by shifting the Stem cell 1 to a Stem cell
2, making this the mechanism of protection conferred by early full-term
pregnancy. In order to elucidate the molecular pathways through which pregnancy
exerts a protective effect, we have analyzed the genomic profile of Lob 1
present in reduction mammoplasty specimens obtained from parous and nulliparous
postmenopausal women. The genes differentially expressed are related to
immune-surveillance, DNA repair, programmed cell death, transcription, and
chromatin structure/activators/co-activator. In the present study we performed
real-time RT-PCR using a low-density array or a microfluid card for genes
related to the immune system and programmed cell death, using 18S as an
internal control [TaqMan(R) Low Density Array Human Immune Panel (Applied
Biosystems)]. Breast epithelial cells from parous women significantly
overexpressed 17 out of 20 genes (p<0.001) with respect to the nulliparous
breast. BCL2-associated X protein, Complement component 3, CD45 antigen,
glyceraldehyde-3-phosphate dehydrogenase, granulysin, and chemokine (C-C motif)
ligand 19 were expressed more than 30-fold with respect to nulliparous breast
cells. Only three out of 20 genes [selectin P (granule membrane protein 140
kDa, antigen CD62), Fas (TNF receptor superfamily, member 6) and chemokine
(C-X-C motif) ligand 11], were downregulated in parous breast with respect to
nulliparous breast cells. The data lead us to conclude that an early pregnancy,
by shifting the Stem cell 1 to Stem cell 2, makes the latter more easily
recognized by the immune-surveillance system, which initiates the programmed
cell death pathway if exposure to toxic or carcinogenic agents occurs.
Clin Sci (Lond). 2007 Jul 4; [Epub
ahead of print]
Relations of waist and hip circumference with coagulation and
fibrinolysis in postmenopausal women.
Peverill RE, Teede HJ, Malan E, Kotsopoulos D, Smolich JJ, McGrath BP.
The contribution of obesity to
the occurrence of cardiovascular events may not be wholly related to its
influence on traditional risk factors. Coagulation and fibrinolysis may also
influence cardiovascular risk, but the relationship of adiposity with these
processes is unclear. The aim of this study was to investigate the
relationships of body mass index (BMI), waist circumference, hip circumference
and waist-to-hip ratio (WHR) with factor VII activity (VIIc), plasma markers of
thrombin generation (prothrombin fragment 1+2; F1+2), fibrin formation (soluble
fibrin; SF) and fibrin turnover (D-dimer), and plasminogen activator
inhibitor-1 (PAI-1; a marker of fibrinolytic inhibitory capacity). The study
cohort was 80 healthy postmenopausal women who were not diabetic, current
smokers or taking hormone therapy and who had a fasting sample of blood
collected. VIIc, F1+2, SF and PAI-1 were all positively correlated with BMI,
waist circumference and WHR, while D-dimer was positively correlated with waist
circumference and WHR, but not BMI. WHR was the strongest correlate of all the
markers except for PAI-1 which was most closely related to BMI. Hip
circumference was a negative correlate of F1+2 and D-dimer after adjusting for
waist circumference. The relationships of WHR with F1+2 and SF, but not with
VIIc and D-dimer, were independent of traditional risk factors. The positive
association between waist circumference and markers of thrombin generation,
fibrin production and fibrin turnover suggests that abdominal adiposity may
contribute to atherothrombosis by activating intravascular coagulation. In
contrast, a larger hip circumference appears to have a protective affect
against coagulation activation.
Expert Rev Cardiovasc Ther. 2007
Jul;5(4):777-789.
Sex hormone replacement therapy and modulation of vascular function in
cardiovascular disease.
Brigham and Women’s Hospital,
Division of Vascular Surgery,
Epidemiological and
experimental studies suggest vascular protective effects of estrogen.
Cardiovascular disease (CVD) is less common in premenopausal women than in men
and postmenopausal women. Cytosolic/nuclear estrogen receptors (ERs) have been
shown to mediate genomic effects that stimulate endothelial cell growth but
inhibit vascular smooth muscle proliferation. However, the Heart and
Estrogen/Progestin Replacement Study (HERS), HERS-II and Women's Health
Initiative clinical trials demonstrated that hormone replacement therapy (HRT)
may not provide vascular benefits in postmenopausal women and may instead
trigger adverse cardiovascular events. HRT may not provide vascular benefits
because of the type of hormone used. Oral estrogens are biologically
transformed by first-pass metabolism in the liver. By contrast, transdermal
preparations avoid first pass metabolism. Also, natural estrogens and
phytoestrogens may provide alternatives to synthetic estrogens. Furthermore,
specific ER modulators could minimize the adverse effects of HRT, including
breast cancer. HRT failure in CVD could also be related to changes in vascular
ERs. Genetic polymorphism and postmenopausal decrease in vascular ERs or the
downstream signaling mechanisms may reduce the effects of HRT. HRT in the late
postmenopausal period may not be as effective as during menopausal transition.
Additionally, while HRT may aggravate pre-existing CVD, it may thwart its
development if used in a timely fashion. Lastly, the vascular effects of
progesterone and testosterone, as well as modulators of their receptors, may
modify the effects of estrogen and thereby provide alternative HRT strategies.
Thus, the beneficial effects of HRT in postmenopausal CVD can be enhanced by
customizing the HRT type, dose, route of administration and timing depending on
the subject's age and cardiovascular condition.
Arch Gynecol Obstet. 2007 Jun 29; [Epub
ahead of print]
Tibolone and osteoporosis.
Lazovic G, Radivojevic U, Milosevic V, Lazovic A, Jeremic K, Glisic A.
BACKGROUND: We conducted a
5-year prospective, observational, controlled study to assess the effects of
tibolone 1.25 mg/day on bone mineral density (BMD) in postmenopausal women with
osteopenia or osteoporosis. METHODS: The subjects were 420 women, an average of
66.4 years old, who had been postmenopausal between 8 and 19 years when
enrolled in the study. Of the 420 women enrolled, 346 agreed to take tibolone
for 5 years. The 74 who refused tibolone took only calcium/vitamin D
supplements and served as the control group. BMD was measured in the lumbar
spine and total hip region at baseline and annually by dual-energy X-ray
absorptiometry (DXA). RESULTS: At the first two follow-up visits, women taking
tibolone had a significant increase in BMD at the spine (P < 0.001) and at
the hip (P < 0.001) when compared to baseline values and when compared to
BMD values for the control group, which decreased from baseline. In the final 3
years of the study, BMD values (spine and hip) continued to decrease in the
control group and also tended to decrease in the tibolone group, but at the end
of the fifth year, mean BMD in the tibolone group was still higher than BMD
before the start of tibolone treatment (P < 0.05). Calculations showed that
if women taking tibolone continued to lose BMD at the same rate as during the
final 3 years of the study, after 11 years of tibolone treatment the average
patient would have the same BMD as she had when treatment started. CONCLUSION:
This 5-year observational study provides evidence that tibolone is effective in
increasing BMD in postmenopausal women with osteopenia and osteoporosis during
the first 2 years of treatment, but because BMD starts to decline in the third
year, it is vital that postmenopausal women start treatment with tibolone as
early as possible, so that bone mineral density levels are kept high as long as
possible.
Int J Gynaecol Obstet. 2007 Jun 28; [Epub
ahead of print]
Effects of tibolone on health-related quality of life in menopausal
women.
Department of Obstetrics and
Gynecology, Vivekananda Institute of Medical Sciences,
OBJECTIVE: The present study
assessed improvements in health-related quality of life (HRQOL) in menopausal
women using tibolone. METHODS: One hundred women who underwent surgical
menopause for various benign gynecological conditions were advised to take
tibolone (2.5 mg) daily. The Menopause Rating Scale (MRS II) was used to assess
the change in HRQOL after 3 months and 12 months of treatment. RESULTS:
Sixty-two women returned for follow-up after 3 months, while only 15 returned
for after 12 months. Significant improvements in HRQOL were found after 3
months, and further improvements were obtained after 12 months, although at a
slower rate. Among the three subscales of MRS, maximum improvement in the
somatovegetative component and lesser improvements in the other two subscales
were found. CONCLUSION: Tibolone is effective in improving the overall HRQOL of
menopausal women. Somatovegetative symptoms show most improvement.
J Am Diet Assoc. 2007
Jul;107(7):1155-65.
Predictors of Dietary Change and Maintenance in the Women's Health
Initiative Dietary Modification Trial.
Tinker LF, Rosal MC, Young AF, Perri MG, Patterson RE, Van Horn L, Assaf AR, Bowen DJ, Ockene J, Hays J, Wu L.
OBJECTIVE: To identify
predictors of dietary change to and maintenance of a low-fat eating pattern
(<20% energy from fat, >/=5 servings fruits/vegetables daily, and >/=6
servings grains daily) among a cohort of postmenopausal women. Candidate
predictors included intrapersonal, interpersonal, intervention program
characteristics, and clinical center. DESIGN: Longitudinal study within the
Women's Health Initiative Dietary Modification Trial. Dietary change was
evaluated after 1 year of participation in the Women's Health Initiative
Dietary Modification Trial, and dietary maintenance after 3 years. SUBJECTS:
Postmenopausal women aged 50 to 79 years at baseline who were randomized to the
intervention arm of the Women's Health Initiative Dietary Modification Trial
(n=19,541). STATISTICAL ANALYSIS: Univariate and multivariate linear regression
analysis was performed and associations evaluated between candidate predictors
and each of the three dietary goals: percent energy from fat, fruit/vegetable
servings, and grain servings. RESULTS: Year 1 (change) predictors of percent
energy from fat (P<0.005) included being younger (beta=2.12; 70 to 79 years
vs 50 to 59 years), more educated (beta=-.69; college vs high school), more
optimistic (beta=-.07), attending more sessions (beta=-.69), and submitting
more self-monitoring records (beta=-.74). At year 3 (maintenance), the predictors
of percent energy from fat (P<0.005) included attending more sessions
(beta=-.65) and submitting more self-monitoring scores (beta=-.71). The
analytic model predicted 22% of the variance in fat intake at year 1 and 27% at
year 3 (P<0.01). CONCLUSIONS: The strongest predictors of dietary change and
maintenance were attending intervention sessions and self-monitoring dietary
intake. Novel was the finding that optimism predicted dietary change.
Bone. 2007 Jun 5; [Epub ahead of print]
Differences in bone mineral status between urban and rural Chinese men
and women.
Gu W, Rennie KL, Lin X, Wang Y, Yu Z.
Institute for Nutritional
Sciences,
BACKGROUND:: Few studies have
investigated differences in bone health and associated lifestyle factors
between urban and rural populations in countries, such as