Selección de Resúmenes de Menopausia
Marzo de 2010
Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile
Semana
del 24 al 30 de Marzo de 2010
J Public Health (Oxf). 2010 Mar 28. [Epub ahead of print]
What was the immediate impact on population health of the recent fall in
hormone replacement therapy prescribing in England? Ecological study.
Martin RM, Wheeler BW,
Metcalfe C, Gunnell D.
Department of Social Medicine,
University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
BACKGROUND: The publication in
2002 of the women's health initiative (WHI) trial revealed long-term risks and
benefits of hormone replacement therapy (HRT). Increased cardiovascular
disease, venous thromboembolism and breast cancer risks outweighed benefits on
hip fracture, colorectal and endometrial cancer. We investigated whether the
subsequent 50% fall in HRT use in England impacted on population rates of these
outcomes. METHODS: Time-series analysis of hospital admissions, incidence and
mortality amongst women aged 50-69, England 1997-2006. RESULTS: There was no
relationship between reduced HRT prescribing after 2002 and trends in breast
cancer, colorectal cancer or hip fracture. Amongst 50-59 year olds, the annual percentage
change in venous thromboembolism hospitalizations fell from 0.0% [95%
confidence interval (CI): -2.3 to 2.3%] between 1997 and 2000 to -5.7% (-7.7 to
-3.6%) between 2000 and 2006 (P-value = 0.001); the annual change in
endometrial cancer mortality increased from 0.7% (-3.2 to 4.8%) between 1997
and 2003 to 11.0% (0.2 to 22.9%) after 2003 (P-value = 0.07); and previously
falling acute myocardial infarction hospitalizations (annual change: -6.8%) and
stroke (-3.0%) stabilized (-0.4%) or increased (+0.8%), respectively, around
2001 (P < 0.0001). CONCLUSION: Although rates of venous thromboembolism
(decline) and endometrial cancer mortality (increase) changed in line with WHI
findings, the decline in venous thromboembolism may have started before 2002
and increased fatal endometrial cancers could be a chance finding.
Calcif Tissue Int. 2010 Mar 28. [Epub ahead of print]
Suppression of C-Terminal Telopeptide in Hypovitaminosis D Requires
Calcium as Well as Vitamin D.
Thomas SD, Need AG, Nordin BE.
Chemical Pathology, SA
Pathology, Frome Road, Adelaide 5000, Adelaide, SA, Australia.
We compared the effects of
oral calcium and vitamin D separately and together on relevant variables in 22
postmenopausal volunteers with initial serum 25OHD levels below 60 nmol/L.
Subjects were allocated randomly to two regimens: group 1 received 1 week of
calcium 1,000 mg, followed by 7 weeks with additional vitamin D(3) 1,000 i.u.
daily; group 2 received 7 weeks of D(3) 1,000 i.u. daily, followed by 1 week
with additional calcium 1,000 mg. We measured serum calcium, phosphate, PTH,
25OHD, CTX, and ALP at baseline and after 1 and 8 weeks in group 1 and after 7
and 8 weeks in group 2. There were no significant changes in ALP from either
vitamin D or calcium. Calcium caused significant elevation of serum 25OHD as
well as major suppression of serum CTX, which could not easily be accounted for
by suppression of PTH. Vitamin D caused no significant change in any variable
except elevation of serum 25OHD. The suppressive effect of calcium (whether
given first or second) on serum CTX was threefold greater than that of vitamin
D (whether given first or second) (P < 0.001), although their suppressive
effects on serum PTH were the same. Calcium and vitamin D yielded greater and
more significant effects on all variables (except ALP) than either treatment
alone. We suggest that calcium may elevate serum 25OHD by prolonging its
half-life and that it may have an inhibitory effect on bone resorption
independent of, or in addition to, its suppression of PTH.
BMC Musculoskelet Disord. 2010 Mar 26;11(1):59. [Epub ahead of print]
Contributions of lean mass and fat mass to bone mineral density: A study
in postmenopausal women.
Ho-Pham LT, Nguyen ND, Lai TQ,
Nguyen TV.
ABSTRACT: BACKGROUND: The relative
contribution of lean and fat to the determination of bone mineral density (BMD)
in postmenopausal women is a contentious issue. The present study was
undertaken to test the hypothesis that lean mass is a better determinant of BMD
than fat mass. METHODS: This cross-sectional study involved 210 postmenopausal
women of Vietnamese background, aged between 50 and 85 years, who were randomly
sampled from various districts in Ho Chi Minh City (Vietnam). Whole body scans,
femoral neck, and lumbar spine BMD were measured by DXA (QDR 4500, Hologic
Inc., Waltham, MA). Lean mass (LM) and fat mass (FM) were derived from the
whole body scan. Furthermore, lean mass index (LMi) and fat mass index (FMi)
were calculated as ratio of LM or FM to body height in metre squared (m2).
RESULTS: In multiple linear regression analysis, both LM and FM were
independent and significant predictors of BMD at the spine and femoral neck.
Age, lean mass and fat mass collectively explained 33% variance of lumbar spine
and 38% variance of femoral neck BMD. Replacing LM and FM by LMi and LMi did
not alter the result. In both analyses, the influence of LM or LMi was greater
than FM and FMi. Simulation analysis suggested that a study with 1000
individuals has a 78% chances of finding the significant effects of both LM and
FM, and a 22% chances of finding LM alone significant, and zero chance of
finding the effect of fat mass alone. CONCLUSIONS: These data suggest that both
lean mass and fat mass are important determinants of BMD. For a given body size
-- measured either by lean mass or height --women with greater fat mass have
greater BMD.
Obesity (Silver Spring). 2010 Mar 25. [Epub ahead of print]
Abdominal Subcutaneous and Visceral Adipose Tissue and Insulin Resistance
in the Framingham Heart Study.
Preis SR, Massaro JM, Robins
SJ, Hoffmann U, Vasan RS, Irlbeck T, Meigs JB, Sutherland P, D'Agostino Sr RB,
O'Donnell CJ, Fox CS.
[1] National Heart, Lung, and
Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA [2]
Center for Population Studies, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, Maryland, USA.
Insulin resistance is
associated with central obesity and an increased risk of cardiovascular
disease. Our objective is to examine the association between abdominal
subcutaneous (SAT) and visceral adipose tissue (VAT) and insulin resistance, to
determine which fat depot is a stronger correlate of insulin resistance, and to
assess whether there was an interaction between SAT, VAT, and age, sex, or BMI.
Participants without diabetes from the Framingham Heart Study (FHS), who
underwent multidetector computed tomography to assess SAT and VAT (n = 3,093;
48% women; mean age 50.4 years; mean BMI 27.6 kg/m(2)), were evaluated. Insulin
resistance was measured using the homeostasis model and defined as HOMA(IR)
>/=75th percentile. Logistic regression models, adjusted for age, sex,
smoking, alcohol, menopausal status, and hormone replacement therapy use, were
used to assess the association between fat measures and insulin resistance. The
odds ratio (OR) for insulin resistance per standard deviation increase in SAT
was 2.5 (95% confidence interval (CI): 2.2-2.7; P < 0.0001), whereas the OR
for insulin resistance per standard deviation increase in VAT was 3.5 (95% CI:
3.1-3.9; P < 0.0001). Overall, VAT was a stronger correlate of insulin
resistance than SAT (P < 0.0001 for SAT vs. VAT comparison). After
adjustment for BMI, the OR of insulin resistance for VAT was 2.2 (95% CI:
1.9-2.5; P < 0.0001). We observed an interaction between VAT and BMI for
insulin (P interaction = 0.0004), proinsulin (P interaction = 0.003), and
HOMA(IR) (P interaction = 0.003), where VAT had a stronger association in obese
individuals. In conclusion, SAT and VAT are both correlates of insulin
resistance; however, VAT is a stronger correlate of insulin resistance than
SAT.
Obesity (Silver Spring). 2010 Apr 1. [Epub ahead of print]
Markers of Inflammation and Weight Change in Middle-Aged Adults: Results
From the Prospective MONICA/KORA S3/F3 Study.
Holz T, Thorand B, Döring A, Schneider A,
Meisinger C, Koenig W.
Helmholtz Zentrum
München-German Research Center for Environmental Health, Institute of
Epidemiology, Neuherberg, Germany.
We investigated associations
of markers of inflammation such as albumin, fibrinogen, C-reactive protein
(CRP), and white blood cell count (WBCC) with future weight gain and weight
loss in middle-aged adults in order to further elucidate the relationship
between subclinical inflammation and weight change. Data were derived from the
third population-based MONICA (Monitoring of Trends and Determinants in
Cardiovascular Diseases) Augsburg survey (S3) conducted as part of the
multinational World Health Organization MONICA project in 1994-1995 and a
follow-up examination, to which all eligible subjects from S3 were invited in
2004-2005 (F3). In total, 2,792 persons (1,391 men, 1,401 women) aged 25-74
years at baseline were analyzed. Subjects with elevated concentrations of inflammatory
markers were more prone to gain weight during follow-up. The odds ratios (OR)
for a large mean annual weight gain (i.e., on average 1.02 kg/year) was 1.73
(95% confidence interval (CI) 1.27, 2.35) in fully adjusted analyses for
subjects in the highest compared to the lowest quartile of fibrinogen. The
respective ORs were 1.45 (95% CI, 1.08, 1.94) and 1.37 (95% CI, 1.03, 1.82) for
CRP and WBCC. Stratified analyses revealed that associations were strongest
among subjects who quitted smoking during the follow-up period (new quitters).
Associations of inflammatory markers with large mean annual weight loss were
weaker and became nonsignificant after multivariable adjustment. In conclusion,
elevated levels of inflammatory markers are independently associated with
weight gain in middle-aged adults, particularly among new quitters. This
suggests that inflammation plays a key role in the process of weight gain,
especially after smoking cessation.
J Am Diet Assoc. 2010 Apr;110(4):527-34.
Dietary, weight, and psychological changes among patients with obesity,
8 years after gastric bypass.
Kruseman M, Leimgruber A,
Zumbach F, Golay A.
Nutrition and Dietetics
Department, School of Health Professions, R. Caroubiers 25, 1227 Carouge,
Switzerland. Maaike.Kruseman@hesge.ch
BACKGROUND AND OBJECTIVE:
Long-term data on patients with obesity outcome after bariatric surgery are
lacking. The goal was to document dietary and anthropometric changes more than
5 years after surgery, as well as patients' eating behavior, psychological
state, and quality of life. METHODS: A cohort of 80 women (mean age 40+/-10
years) who underwent a Roux-en-Y gastric bypass between 1997 and 2002 were
followed in a Swiss University Hospital for an average of 8+/-1.2 years. The
primary outcome was successful weight loss defined as excess weight loss
>or=50%. Body composition was measured by bioelectrical analysis, and diet
was assessed via a food diary. Eating disorders, psychological factors, and
quality of life were evaluated by questionnaires. Patients' perceptions of
difficulties and benefits were explored using semistructured interviewing.
Results at baseline and last visit were compared using paired t test.
Cofactors' means were compared between successful and unsuccessful patients
with Student t tests and logistic regression. RESULTS: Average weight loss 8
years after surgery was 30.7+/-13.8 kg. Excess weight loss >or=50% was
observed for 47 patients (59%). Between baseline and last visit, relative
proportions of fat mass/total body weight decreased, and fat-free mass/total
body weight increased. Mean energy intake was 2,355+/-775 kcal at baseline and
1,680+/-506 kcal at last visit, with 42% of energy from carbohydrates, 39% of
energy from fats, and 19% of energy from protein (0.8 g/kg). At last visit, 41
patients (51%) described episodes of binge eating or night eating syndrome.
Factors associated with excess weight loss >or=50% were: younger age at
operation, greater number of psychological consultations before the operation,
and higher scores on ineffectiveness and social insecurity scales at baseline.
CONCLUSIONS: More than half of the patients achieved successful weight loss,
but disordered eating behavior was frequent. Periodic follow-up screenings and
interdisciplinary care are advised. The definition of successful outcome should
take into account problematic eating behaviors.
BMJ. 2010 Mar
23;340:c1241. doi: 10.1136/bmj.c1241.
Breast cancer mortality in organised mammography screening in Denmark:
comparative study.
Jřrgensen KJ, Zahl PH, Gřtzsche PC.
The Nordic Cochrane Centre,
Rigshospitalet, University of Copenhagen, Denmark. kj@cochrane.dk
OBJECTIVE: To determine
whether the previously observed 25% reduction in breast cancer mortality in
Copenhagen following the introduction of mammography screening was indeed due
to screening, by using an additional screening region and five years additional
follow-up. DESIGN: We used Poisson regression analyses adjusted for changes in
age distribution to compare the annual percentage change in breast cancer
mortality in areas where screening was used with the change in areas where it
was not used during 10 years before screening was introduced and for 10 years
after screening was in practice (starting five years after introduction of
screening). SETTING: Copenhagen, where mammography screening started in 1991,
and Funen county, where screening was introduced in 1993. The rest of Denmark
(about 80% of the population) served as an unscreened control group.
PARTICIPANTS: All Danish women recorded in the Cause of Death Register and
Statistics Denmark for 1971-2006. MAIN OUTCOME MEASURE: Annual percentage
change in breast cancer mortality in regions offering mammography screening and
those not offering screening. RESULTS: In women who could benefit from
screening (ages 55-74 years), we found a mortality decline of 1% per year in
the screening areas (relative risk (RR) 0.99, 95% confidence interval (CI) 0.96
to 1.01) during the 10 year period when screening could have had an effect
(1997-2006). In women of the same age in the non-screening areas, there was a
decline of 2% in mortality per year (RR 0.98, 95% CI 0.97 to 0.99) in the same
10 year period. In women who were too young to benefit from screening (ages
35-55 years), breast cancer mortality during 1997-2006 declined 5% per year (RR
0.95, CI 0.92 to 0.98) in the screened areas and 6% per year (RR 0.94, CI 0.92
to 0.95) in the non-screened areas. For the older age groups (75-84 years),
there was little change in breast cancer mortality over time in both screened
and non-screened areas. Trends were less clear during the 10 year period before
screening was introduced, with a possible increase in mortality in women aged
less than 75 years in the non-screened regions. CONCLUSIONS: We were unable to
find an effect of the Danish screening programme on breast cancer mortality.
The reductions in breast cancer mortality we observed in screening regions were
similar or less than those in non-screened areas and in age groups too young to
benefit from screening, and are more likely explained by changes in risk
factors and improved treatment than by screening mammography.
Semana
del 17 al 23 de Marzo de 2010
Climacteric. 2010 Apr;13(2):103-20.
Therapeutic options for postmenopausal female sexual dysfunction.
Al-Azzawi F, Bitzer J, Brandenburg U, Castelo-Branco C, Graziottin A,
Kenemans P, Lachowsky M, Mimoun S, Nappi RE, Palacios S, Schwenkhagen A, Studd
J, Wylie K, Zahradnik HP.
Gynaecology Research Unit, Victoria Building, University Hospitals of
Leicester, Leicester, UK.
BACKGROUND: Female sexual dysfunction (FSD) is a multidimensional
problem combining biological, psychological and interpersonal elements of
multiple etiologies. Menopause-related sexual dysfunction may not be reversible
without therapy. Hormonal deficiency does not usually decrease in severity over
time. Many options are available for the successful treatment of postmenopausal
FSD. OBJECTIVE: To review the pharmacological and non-pharmacological therapies
available for postmenopausal FSD, focusing on practical recommendations for
managing postmenopausal women with sexual complaints, through a literature
review of the most relevant publications in this field. PSYCHOSOCIAL THERAPY:
This type of therapy (basic counselling, physiotherapy and psychosexual
intervention) is considered an adaptable step-by-step approach for diagnostic
and therapeutic strategies, normally combined with biomedical interventions to
provide optimal outcomes. PHARMACOLOGICAL THERAPY: For postmenopausal FSD, many
interventional options are now available, including hormonal therapies such as
estrogens, testosterone, combined estrogen/testosterone, tibolone and
dehydroepiandrosterone. CONCLUSIONS: Menopause and its transition represent
significant risk factors for the development of sexual dysfunction. FSD impacts
greatly on a patient's quality of life. Consequently, it is receiving more
attention thanks to the development of effective treatments.
Non-pharmacological approaches should be used first, focusing on lifestyle and
psychosexual therapy. If required, proven effective hormonal and non-hormonal
therapeutic options are available.
Maturitas. 2010
Apr;65(4):301-7. Epub 2010 Jan 29.
Molecular biology of bone remodeling: implications for new therapeutic
targets for osteoporosis.
Gallagher JC, Sai AJ.
Creighton University Medical Center, Bone
Metabolism Unit, Omaha, NE 68131, USA. jcg@creighton.edu
Osteoporosis is a major public health problem
for adults over age 55 years costing billions of euros/dollars. Over the last
20 years anti-resorptive drugs were the treatment of choice for osteoporosis
and most were derived from the bisphosphonate molecule. In the last 7 years
remarkable advances in molecular biology and genetics have led to a detailed
understanding of the bone remodeling cycle and as a result new therapeutic
targets for treatment emerged. These new compounds have different modes of
action depending on their role in the bone remodeling cycle. A major discovery
was the important role of RANKL (receptor activator of nuclear factor kappa B
ligand) secreted by osteoblasts and responsible for stimulating osteoclastic
bone resorption. This led to development of a potent monoclonal antibody that
blocks its action. This drug should be available soon as a new treatment for
osteoporosis. Other molecular targets in resorption have been identified and
several specific antagonists are potential treatments. However, a significant
limiting factor for a new anti-resorptive drug is the cost of bringing it to
the market because of the huge costs of a fracture trial. Although
anti-resorptive agents have been the backbone of osteoporosis treatment they do
not rebuild bone architecture and development of anabolic agents is needed.
These are likely to evolve from an understanding of the LRP/Wnt signaling
pathway. Already an antibody against sclerostin has shown promise in animal
studies, and not to forget parathyroid hormone which was the first clinically
useful anabolic treatment for osteoporosis.
Eur J Pharmacol. 2010 Apr 25;632(1-3):93-102.
Epub 2010 Feb 2.
KR-003048, a potent, orally active inhibitor of p38
mitogen-activated protein kinase.
Montalban AG, Boman E, Chang CD, Ceide SC, Dahl R, Dalesandro D, Delaet
NG, Erb E, Ernst J, Gibbs A, Kahl J, Kessler L, Lundström J, Miller S,
Nakanishi H, Roberts E, Saiah E, Sullivan R, Wang Z, Larson CJ.
Drug Discovery, Kemia, Inc., San Diego, CA, United States.
The tumor necrosis factor-alpha (TNF-alpha) cytokine, secreted by
activated monocytes/macrophages and T lymphocytes, is implicated in several
diseases, including rheumatoid arthritis, chronic obstructive pulmonary
disease, inflammatory bowel disease, and osteoporosis. Monocyte/macrophage
production of TNF-alpha is largely driven by p38alpha mitogen-activated protein
kinase (MAP kinase), an intracellular soluble serine-threonine kinase. p38alpha
MAP kinase is activated by growth factors, cellular stresses, and cytokines
such as TNF-alpha and interleukin-l (IL-I). The primary contribution of
p38alpha activation to excess TNF-alpha in settings of both chronic and acute
inflammation has instigated efforts to find inhibitors of this enzyme as
possible therapies for associated disease states. Analogue design, synthesis,
and structure-activity studies led to the identification of 5-tert-butyl-N-cyclopropyl-2-methoxy-3-{2-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-2-oxo-acetylamino}-benzamide
(KR-003048) as a potent inhibitor of the p38 MAP kinase signaling pathway in
vitro and in vivo. The inhibition in vitro of human p38alpha enzyme activity
and lipopolysaccharide (LPS)-induced p38 activation and subsequent TNF-alpha
release is described. KR-00348 was demonstrated to be a potent inhibitor of
inflammatory cytokine production ex vivo in rat and human whole blood, and
showed good oral bioavailability. Additionally, efficacy in mouse and rat
models of acute and chronic inflammation was obtained. KR-003048 possessed
therapeutic activity in acute models, demonstrating substantial inhibition of
carrageenan-induced paw edema and in vivo LPS-induced TNF release at 30mg/kg
p.o. Collagen-induced arthritis in mice was significantly inhibited by 10 and
30mg/kg doses of KR-003048. Evidence for disease-modifying activity in this
model was indicated by histological evaluation of joints. 2010 Elsevier B.V.
Osteoporos Int. 2010 Apr;21(4):561-8. Epub
2009 Jun 30.
Population screening for osteoporosis risk: a
randomised control trial of medication use and fracture risk.
Barr RJ, Stewart A, Torgerson DJ, Reid DM.
Bone and Musculoskeletal Research Programme, University of Aberdeen,
Foresterhill, Aberdeen, UK.
Randomised control trial of osteoporosis screening in 4,800 women aged
45-54 years was carried out. Screened group observed an increase of 7.9% in
hormone replacement therapy (HRT) use (p < 0.001), 15% in other osteoporosis
treatments (p < 0.001) and a 25.9% reduction in fracture risk compared with
control. Screening for osteoporosis significantly increases treatment use and
reduces fracture incidence. INTRODUCTION: Population screening programmes can
identify menopausal women with low bone mineral density (BMD) and elevated risk
of future fracture but require to be proven effective by a randomised control
trial. METHODS: A total of 4,800 women, 45-54 years, were randomised in equal
numbers to screening or no screening (control) groups. Following screening,
those in the lowest quartile of BMD were advised to consider HRT. Nine years
later, the effect of screening on the uptake of treatment and the incidence of
fractures were assessed by postal questionnaire. Categorical differences were
assessed using chi(2) test. Cox regression was used to assess hazard ratio
(HR). RESULTS: Of the screened and the control groups, 52.4% vs 44.5%,
respectively, reported taking HRT (p < 0.001). In addition, 36.6% of the screened
vs 21.6% of the control groups reported the use of vitamin D, calcium,
alendronate, etidronate or raloxifene (p < 0.001). In a per protocol
analysis of verified incident fractures, a 25.9% reduction in risk of fractures
(of any site) in the screened group was observed (HR = 0.741, 95% CI =
0.551-0.998 adjusted age, weight and height). CONCLUSIONS: Screening for
osteoporosis as assessed by low bone density significantly increases the use of
HRT and other treatments for osteoporosis and reduces fracture incidence.
Menopause. 2010
Mar 17. [Epub ahead of print]
Early menopausal hormone use influences brain regions used for visual
working memory.
Berent-Spillson A, Persad CC, Love T, Tkaczyk
A, Wang H, Reame NK, Frey KA, Zubieta JK, Smith YR.
From the 1Molecular and Behavioral
Neuroscience Institute, 2Reproductive Sciences Program, Department of
Obstetrics and Gynecology, and 3Postdoctoral Translational Scholars Program,
Michigan Institute for Clinical and Health Research, and Departments of 4Psychiatry
and 5Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; and
6School of Nursing, Columbia University, New York, NY.
OBJECTIVE:: The cognitive benefit of
postmenopausal hormone use is controversial; however, timing of treatment close
to menopause may increase the likelihood of preserving cognitive function. We
examined the effects of early-initiation hormone use on visual working memory,
hypothesizing that long-term hormone use is associated with greater brain
activation during visual working memory. METHODS:: This was a cross-sectional
comparison of long-term early hormone users-current (n = 13) and past (n = 24;
2.1 +/- 1.0 years off hormones)-with never users (n = 18), using a visual
memory task and functional magnetic resonance imaging (MRI). We evaluated 55
women older than 60 years at the University of Michigan's General Clinical
Research Center. Hormone users had completed at least 10 continuous years of
conjugated equine estrogens with or without medroxyprogesterone acetate, begun
within 2 years of menopause. Women were excluded for illness, medication,
intermittent estrogen use, phytoestrogen use, recent smoking, and MRI
contraindications. The primary outcome was functional MRI-detected brain
activity during the visual memory task. RESULTS:: Compared with never users,
both groups of hormone users had increased activation in the frontal and
parietal cortices, insula, hippocampus, and cingulate; combined hormone users
also had increased activation in the putamen and raphe (corrected P < 0.05
or uncorrected P < 0.001 with a priori hypothesis). Across the entire
sample, the medial temporal cortex (P < 0.0001 right; P < 0.018 left) and
right hippocampus (P < 0.0001) positively correlated with task performance.
CONCLUSIONS:: Hormone use was associated with increased brain activation during
the visual memory task, in regions used for visual working memory. A positive
correlation between activation and task performance suggests that
early-initiation, long-term postmenopausal hormone use may benefit visual
working memory.
Clin Med Res. 2010 Mar;8(1):58.
PS2-15:
Sex-Specific Differences in the Protective Effect of Statins on Skeletal
Fractures.
Shainline MR, Robinson SB, Gunter MJ,
Carter S, Beaton SJ, Nawarskas J, Bakhireva LN.
Background: Recent reports indicate that
HMG-CoA reductase inhibitors (statins), used for prevention and treatment of
dyslipidemia and CVD, might have a beneficial effect on bone metabolism.
Limitations of previous studies do not allow unequivocal conclusions about
bone-sparing effect of statins. Methods: This study examined statin use and
osteoporosis-related skeletal fractures. Members of a large New Mexico Health
Plan served as the study population (n=7,539). The sample included women >
50 years old and men > 60 years old who had > 1 prescription fill or >
1 encounter with a healthcare provider between 1999 and 2005, but excluded
patients with cancer, osteomalacia, and end stage renal disease. Patients with
incident fractures of the hip, wrist/forearm, and spine occurring between 1999
and 2005 were identified as cases (n=1,880). Controls were selected from the
same population based on timing of enrollment to controls in 1:3 ratio
(n=5,659). The prevalence of statin use (> 3 fills a year prior to the index
date) was compared among study groups by Chi-square analysis in univariate and
by logistic regression in multivariate analyses. To explore duration -response
effect, statin use was classified as current (3 months prior to the index date)
and continuous (> 10 annual fills prior to the index date). Results: The
mean age was 71.4+/-10.2 years among cases and 63.8+/-9.2 among controls, with
72.8% females. 15.9% of cases and 17.1% of controls reported any statin use,
and the most prevalent statins were simvastatin followed by lovastatin,
atorvastatin, and pravastatin. In men, no association between fractures and
either current (OR=0.81; 95% CI: 0.55; 1.20) or continuous statin use (OR=0.86;
95% CI: 0.51; 1.44) was observed after adjustment for age, corticosteroids use,
chronic kidney disease, and comorbidities. In women, significant protective
effect was observed among both current (OR=0.58; 95% CI: 0.44; 0.78) and
continuous (OR=0.66; 95% CI: 0.45; 0.99) statin users independent of age,
corticosteroid use, bisphosphonates, chronic kidney disease, comorbidities, and
postmenopausal hormone therapy. Conclusions: We observed a protective effect of
statins on osteoporosis- related fractures in women but not in men. These
findings suggest sex- specific effect of statins on bone metabolism.
Semana
del 10 al 16 de Marzo de 2010
Trends Endocrinol Metab. 2010 Mar 9. [Epub ahead of print]
What old means to bone.
Manolagas SC,
Parfitt AM.
Division of Endocrinology and Metabolism, Center for Osteoporosis and
Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the
Central Arkansas Veterans Health Care System, Little Rock, AR 72205, USA.
The adverse effects of aging of other organs (ovaries at menopause) on
the skeleton are well known, but ironically little is known of skeletal aging
itself. Evidence indicates that age-related changes, such as
oxidative stress, are fundamental mechanisms of the decline of bone mass and
strength. Unlike the short-lived osteoclasts and osteoblasts, osteocytes -
former osteoblasts entombed in the mineralized matrix - live as long as 50
years, and their death is dependent on skeletal age. Osteocyte death is a major
contributor to the decline of bone strength with age, and the likely mechanisms
are oxidative stress, autophagy failure and nuclear pore "leakiness".
Unraveling these mechanisms should improve understanding of the age-related
increase in fractures and suggest novel targets for its prevention.
Maturitas. 2010 Apr;65(4):386-391. Epub 2009 Dec 29.
Comparative analysis of the uterine and mammary gland effects of
progesterone and medroxyprogesterone acetate.
Otto C, Fuchs I,
Vonk R, Fritzemeier KH.
TRG Women's
Healthcare, Bayer Schering Pharma AG, Muellerstrasse 178, 13342 Berlin,
Germany.
OBJECTIVES: In combined
hormone replacement therapy (HRT) progestins are used to inhibit
estradiol-activated uterine epithelial cell proliferation. In comparison to
estradiol-only therapy, combined HRT leads to enhanced proliferation of mammary
epithelial cells. In a quantitative mouse model, we assessed the balance
between uterine and undesired mammary gland effects for two progestins that are
widely used in HRT, progesterone and medroxyprogesterone acetate. STUDY DESIGN:
Mice were ovariectomized and after 14 days they were treated subcutaneously
with either vehicle, estradiol (100ng) or estradiol plus increasing doses of
progesterone or medroxyprogesterone acetate for three weeks. MAIN OUTCOME
MEASURES: Measures for progestogenic mammary gland activity were stimulation of
side-branching and stimulation of epithelial cell proliferation. Progestogenic
activity in the uterus was assessed by measuring inhibition of
estradiol-activated uterine epithelial cell proliferation. ED(50) and ID(50)
values for the distinct readouts were obtained and dissociation factors for
uterine versus mammary gland activity were calculated. RESULTS: MPA
demonstrated uterine activity and mitogenic activity in the mammary gland at
the same doses. In contrast, progesterone showed uterine activity at doses
lower than those leading to significant stimulation of epithelial cell
proliferation in the mammary gland. CONCLUSIONS: Progestins do not behave the
same. Use of the natural hormone progesterone, but not MPA, in combined hormone
therapy might offer a safety window between uterine effects and undesired
proliferative activity in the mammary gland.
Maturitas. 2010 Apr;65(4):378-382. Epub 2009 Dec 23.
Risk factors related to the presence and severity of hot flushes in
mid-aged Ecuadorian women.
Chedraui P,
Aguirre W, Calle A, Hidalgo L, León-León P, Miranda O, Martínez N, Mendoza M,
Narváez J, Sánchez H, Schwager G, Quintero JC, Zambrano B, Aguilar A, Martínez
MA, Rivera R, Ruilova I.
Research Group
for the Ecuadorian Climacteric & Menopause Society (SECLIM), Ecuador.
BACKGROUND:
Several studies drawn from the Ecuadorian population have previously reported
that more than half of mid-aged women present hot flushes, which can impair
their quality of life. However up-to-date risk factors for their presence and
severity have not been assessed. OBJECTIVE: To assess hot flush frequency and
intensity and related risk factors among middle-aged Ecuadorian women. METHODS:
In this cross-sectional study, 1154 healthy women aged 40-59 years, visiting
healthcare centers of eight main cities of Ecuador with more than 100,000
inhabitants, were assessed with the first item of the Menopause Rating Scale
(MRS) and a questionnaire containing female and partner socio-demographic data.
RESULTS: Mean age of the entire sample was 48.8+/-5.6 years (median 48), a
48.7% had 12 or less years of schooling, 52.8% were postmenopausal, 43.6% lived
at high altitude, 56.8% were married and 10% were on hormonal therapy (HT). Hot
flushes accounted for 56% (n=646) of the whole sample, of which 29.1% and 9.1%
were respectively graded as severe and very severe. Logistic regression
determined that female sedentarism (OR: 2.42, CI 95% [1.63-3.59]), accessing a
free healthcare system (OR: 1.96, CI 95% [1.30-2.96]), living at high altitude
(OR: 1.82, CI 95% [1.14-2.90]) and having a partner abusing alcohol (OR: 1.92,
CI 95% [1.09-3.35]) were significant risk factors related to the presence of
hot flushes. The regression model also determined that among women with hot
flushes (n=646), sedentarism (OR: 1.73, CI 95% [1.14-2.62]) and having a
partner with erectile dysfunction (OR: 2.57, CI 95% [1.44-4.59]) were
significant risk factors related to severe/very severe hot flushes whereas
married status (OR: 0.53, CI 95% [0.32-0.86]), living at high altitude (OR:
0.46, CI 95% [0.26-0.78]) and partner healthiness (OR: 0.59, CI 95%
[0.36-0.95]) were not. CONCLUSION: To the best of our knowledge this is the
first and largest study assessing hot flushes in a mid-aged Ecuadorian
population. We found that the presence and severity were not significantly
related to age and hormonal status yet to other individual female/male
characteristics and the demography of the studied population.
J Bone Miner Res. 2010 Mar 10. [Epub ahead of print]
Microarchitectural deterioration of cortical and trabecular bone:
Differing effects of denosumab and alendronate.
Seeman E, Delmas
PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK,
Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J.
Austin Health,
University of Melbourne, Melbourne, Australia.
The intensity of
bone remodeling is a critical determinant of the decay of cortical and
trabecular microstructure after menopause. Denosumab suppresses remodeling more
than alendronate leading to greater gains in areal bone mineral density (aBMD).
These greater gains may reflect differing effects of each drug on bone
microarchitecture and strength. In a phase 2, double-blind, pilot study, 247
postmenopausal women were randomized to denosumab (60 mg subcutaneous 6
monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All
received daily calcium and vitamin D. Morphologic changes were assessed using
high-resolution peripheral quantitative computed tomography (HR-pQCT) at the
distal radius and distal tibia and QCT at the distal radius. Denosumab
decreased serum C-telopeptide more rapidly and markedly than alendronate. In
the placebo arm, total, cortical, and trabecular BMD, and cortical thickness
decreased (-2.1% to -0.8%) at the distal radius after 12 months. Alendronate
prevented the decline (-0.6% to 2.4%; p = 0.051 to < 0.001 vs placebo),
while denosumab prevented the decline or improved these variables (0.3% to
3.4%; p < 0.001 vs placebo). Changes in total and cortical BMD were greater
with denosumab than alendronate (p </= 0.024). Similar changes in these
parameters were observed at the tibia. The polar moment of inertia also
increased more in the denosumab than alendronate or placebo groups (p <
0.001). Adverse events did not differ by group. These data suggest that
structural decay due to bone remodeling and progression of bone fragility may
be more effectively prevented with denosumab.
Menopause. 2010 Mar 9. [Epub ahead of print]
Effect of exercise and Cimicifuga racemosa (CR BNO 1055) on bone
mineral density, 10-year coronary heart disease risk, and menopausal
complaints: the randomized controlled Training and Cimicifuga racemosa Erlangen
study.
Bebenek M,
Kemmler W, von Stengel S, Engelke K, Kalender WA.
From the
Institute of Medical Physics, University of Erlangen, Erlangen, Germany.
OBJECTIVE:: The
aim of this study was to determine the effect of periodized exercise training
with and without Cimicifuga racemosa (CR) on bone mineral density (BMD) and
10-year coronary heart disease (CHD) risk in early postmenopausal women.
METHODS:: A total of 128 women were randomly assigned to three subgroups:
exercise (EG, n = 43), exercise and CR supplementation (EGCR, n = 43), and
wellness control (control group [CG], n = 42). Both exercise groups performed a
periodized exercise program with high-intensity-resistance/high-impact exercise
dedicated to bone parameters interspersed by blocks of 10 weeks of training
focusing on CHD parameters. In addition to the exercise program, the EGCR was
supplemented with 40 mg/day of CR according to the specification of the
manufacturer. A low-intensity exercise program of 60 minutes per week for a
period of 10 weeks interspersed with 10-week blocks without exercise was
performed in the CG. Primary endpoints were BMD and 10-year CHD risk proposed
by Wilson. Secondary endpoints were body composition and menopausal symptoms.
RESULTS:: BMD at the lumbar spine was maintained in both exercise groups (EG,
-0.1% +/- 2.2%, P = 0.74; EGCR, -0.4% +/- 2.4%, P = 0.40) and significantly
decreased (P < 0.001) in the CG (2.0% +/- 2.0%). Both exercise groups
significantly differed from the CG (P = 0.001 and 0.005 for the EG and EGCR,
respectively); however, no differences between the exercise groups with and
without CR was determined. Although slight increases in femoral neck BMD were
determined in both exercise groups (EG, 0.5% +/- 3.0%, P = 0.36; EGCR, 0.4% +/-
3.1%, P = 0.52), a reduction was assessed in the CG (-0.6% +/- 2.7%, P = 0.29).
No significant differences were determined between the groups. The 10-year CHD
risk significantly increased in the EGCR (12.9% +/- 25.1%, P = 0.018) and in
the CG (16.5% +/- 27.8%, P = 0.007). The EG did not show corresponding changes
(-2.7% +/- 21.9%, P = 0.60). However, no significant between-group differences
were observed. CONCLUSIONS:: In conclusion our exercise program favorably
affected bone, menopausal symptoms, lean body mass, and, to a smaller extent,
10-year CHD risk in early postmenopausal women. Adjuvant supplementation of CR
did not enhance these positive effects.
Diabetes Res Clin Pract. 2010 Apr;88(1):e1-e3. Epub 2010 Feb 8.
Fat mass threshold associated with a significant deterioration of
insulin sensitivity in postmenopausal women.
Bobeuf F,
Aubertin-Leheudre M, Lord C, Labonté M, Khalil A, Dionne IJ.
Research Centre
on Aging, University of Sherbrooke, Sherbrooke, QC, Canada; Faculty of Physical
Education and Sport, University of Sherbrooke, Sherbrooke, QC, Canada.
The aim of this
study was to establish a cut-off value of percentage of fat mass (%FM) at which
insulin sensitivity (IS) is significantly altered in sedentary postmenopausal
women. Our results suggest that maintaining a %FM below 41% would minimize the
deterioration of IS and its associated risks
Toxicol Lett. 2010 Apr 1;193(3):224-228. Epub 2010 Jan 22.
Equine estrogen-induced mammary tumors in rats.
Okamoto Y, Liu
X, Suzuki N, Okamoto K, Kim HJ, Laxmi YR, Sayama K, Shibutani S.
Laboratory of
Chemical Biology, Department of Pharmacological Sciences, State University of
New York at Stony Brook, Stony Brook, NY 11794-8651, USA.
Long-term
hormone replacement therapy is associated with an increased risk of breast,
ovarian and endometrial cancers in women. Equine estrogens are a principal
component of hormone replacement therapy; however, their tumorigenic potential
toward mammary tissue and reproductive organs has not been extensively
explored. A pellet containing equilin was inserted under the skin of female ACI
rats and the development of mammary tumors was monitored. Histological
examination revealed premalignant lesions such as apocrine metaplasia in
whole-mount preparations of mammary gland from the equilin-treated rats. ACI
rats given 10mg equilin developed palpable mammary tumors at 13 weeks of treatment,
and 37.5% of the rats developed mammary tumors within 15 weeks. For 2.5mg
equilin, palpable tumors were observed in 8.3% of the rats after 8 weeks'
treatment; the frequency was lower than that (42.9%) observed with 2.5mg E(2).
No tumors were observed in the untreated rats. Evidently, equilin is a mammary
carcinogen, and this potential may be associated with development of breast and
reproductive cancers in women receiving hormone replacement therapy.
Osteoporos Int. 2010 Apr;21(4):679-88. Epub 2009 Jul 2.
Bisphosphonates and osteoporotic fractures: a cross-design
synthesis of results among compliant/persistent postmenopausal women in
clinical practice versus randomized controlled trials.
Wilkes MM,
Navickis RJ, Chan WW, Lewiecki EM.
Hygeia Associates,
17988 Brewer Rd, Grass Valley, CA, 95949, USA, mwilkes@hygeiaassociates.com.
In a
cross-design synthesis, total fractures were similarly reduced by
bisphosphonates among postmenopausal women in randomized trials (23.8%) and
highly compliant/persistent patients in observational studies of large
databases from routine practice (20.3%). Bisphosphonates also reduced
nonvertebral, vertebral and hip fractures in randomized trials and
observational studies. In the real-word setting, compliant/persistent patients
can gain a benefit from bisphosphonates comparable to that of randomized trial
participants. INTRODUCTION: The purpose of the study was to determine whether
clinical fracture risk reduction by bisphosphonate treatment in women with
postmenopausal osteoporosis differs between randomized controlled trials and
routine practice. METHODS: Randomized trials comparing bisphosphonate with
placebo and observational studies comparing highly compliant/persistent with
less compliant/persistent patients were sought by electronic searches and
ancillary methods. Clinical fracture data were extracted from the study reports
and quantitatively combined by random effects metaanalysis. RESULTS: The odds
ratio (OR) for all clinical fractures in randomized trials of 0.762, with a 95%
confidence interval (CI) of 0.680-0.855, was closely similar to that in the
observational studies (OR, 0.797; CI, 0.748-0.850). Pooled clinical fracture
reduction across both study designs was 22%. Nonvertebral, vertebral, and hip
fractures were also significantly reduced by bisphosphonate treatment in both
randomized trials and observational studies. CONCLUSIONS: Compliant/persistent
patients in the "real-world" setting benefit from bisphosphonate
treatment to a similar extent as patients in randomized trials.
Semana del 3 al 9 de Marzo de 2010
Osteoporos
Int. 2010 Mar 4. [Epub ahead of print]
Effect of calcium and vitamin D supplementation on bone mineral density
in women aged 65-71 years: a 3-year randomized population-based trial (OSTPRE-FPS).
Kärkkäinen M, Tuppurainen M,
Salovaara K, Sandini L, Rikkonen T, Sirola J, Honkanen R, Jurvelin J, Alhava E,
Kröger H.
Bone and Cartilage Research
Unit, Mediteknia Building, University of Kuopio, P.O. Box 1627, 70211, Kuopio,
Finland, Matti.Karkkainen@uku.fi.
The Osteoporosis Risk Factor
and Prevention-Fracture Prevention Study (OSTPRE-FPS) was a randomized
population-based open trial (n = 593). The supplementation group (n = 287)
received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the
control group (n = 306) received neither supplementation nor placebo. Daily
vitamin D and calcium supplementation have a positive effect on the skeleton in
ambulatory postmenopausal women. INTRODUCTION: Vitamin D deficiency is common
in the elderly, and vitamin D levels are associated with low bone mineral
density (BMD). The working hypothesis was that vitamin D and calcium
supplementation could prevent bone loss in ambulatory postmenopausal women.
METHODS: The OSTPRE-FPS was a randomized population-based open trial with a
3-year follow-up in 3,432 women (aged 66 to 71 years). A randomly selected
subsample of 593 subjects underwent BMD measurements. The supplementation group
(n = 287) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years
while the control group (n = 306) received neither supplementation nor placebo.
RESULTS: In the intention-to-treat analysis, total body BMD (n = 362) increased
significantly more in the intervention group than in the control group (0.84%
vs. 0.19%, p = 0.011). The BMD change differences at the lumbar spine (p =
0.372), femoral neck (p = 0.188), trochanter (p = 0.085), and total proximal
femur (p = 0.070) were statistically nonsignificant. Analyses in compliant
women (>/=80% of use) resulted in stronger and statistically significant
effects at the total body and femoral regions. CONCLUSION: Daily vitamin D and
calcium supplementation have a positive effect on the skeleton in ambulatory
postmenopausal women with adequate nutritional calcium intake.
Climacteric. 2010 Mar 1. [Epub ahead of print]
Severe menopausal symptoms in mid-aged Latin American women can be
related to their indigenous ethnic component.
Ojeda E, Monterrosa A, Blümel
JE, Escobar-López J, Chedraui P.
Collaborative Group for Research
of the Climacteric in Latin America (REDLINC).
Background Latin American
women present more severe menopausal symptoms when compared to those from other
regions of the world. Since this population is an ethnic blend of Caucasian and
indigenous people, we sought to test the hypothesis that severe menopausal
symptoms in Latin American women are associated with an indigenous origin.
Objective To assess menopausal symptoms among two specific indigenous Latin
American populations. Method A total of 573 natural postmenopausal indigenous
women aged 45-59 years (288 Quechua (Peru) and 285 Zenú (Colombia)) living in
isolated communities were surveyed with a general questionnaire and the
Menopause Rating Scale (MRS). Results The total MRS score was significantly
higher among Quechua women as compared to Zenú ones (22.7 +/- 5.7 vs. 14.7 +/-
2.5, p < 0.0001); both figures were higher than those described for Hispanic
or European populations. Quechua women presented more intense somatic and
psychological symptoms as compared to Zenú (8.8 +/- 2.3 vs. 5.3 +/- 1.8; and
7.8 +/- 2.4 vs. 3.2 +/- 1.7, p < 0.0001); however, both indigenous groups
presented similar intense urogenital symptoms (6.1 +/- 1.6 vs. 6.2 +/- 1.4, not
significant). These differences persisted after adjusting for age, years since
menopause onset and parity. The percentage of women presenting severe somatic
and psychological symptoms significantly increased with aging among Quechua.
This was not the case for Zenú women. More than 90% of indigenous women
(Quechua and Zenú) at all age intervals presented severe urogenital scores, a
percentage that is much higher than that described in the world literature.
Conclusion Severe menopausal symptoms found among Latin American women could be
the result of their indigenous ethnic origin; the urogenital domain is the most
affected.
J Endocrinol. 2010 Mar 2. [Epub ahead of print]
The GH/IGF-I axis and signaling pathways in the muscle and bone:
mechanisms underlying age-related skeletal muscle wasting and osteoporosis.
Perrini S, Laviola L, Carreira
M, Cignarelli A, Natalicchio A, Giorgino F.
S Perrini, Emergency and Organ
Transplantation, Section of Internal Medicine, Endocrinology, Andrology and
Metabolic Diseases, University of Bari, Bari, Italy.
Widespreasd increase in life
expectancy is accompanied by an increased prevalence of features of physical
frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced
exercise capacity, and diminished sense of well-being. The pathogenesis of
age-associated sarcopenia and osteopenia is multifactorial, and hormonal
decline may be a contributing factor. Aging is associated with a progressive
decrease in growth hormone (GH) secretion, and more than 30% of elderly people
have circulating IGF-I levels below the young-normal range. GH acts directly on
target tissues, including skeletal muscle and bone among many others, but many
effects are mediated indirectly by circulating (liver-derived) or locally
produced IGF-I. Aging is also associated with reduced insulin sensitivity
which, in turn, may contribute to the impairment of IGF-I action. Recent
experimental evidence suggests that, besides the age-dependent decline of GH
and IGF-I serum levels, the dysregulation of GH and IGF-I actions due to
impairment in the post-receptor signaling machinery may contribute to the loss
of muscle mass and osteopenia. This article will focus on the molecular
mechanisms of impaired GH and IGF-I signaling and action in aging and their
role in the pathogenesis of sarcopenia and osteoporosis.
Gynecol Endocrinol. 2010 Mar 2. [Epub ahead of print]
Low-dose vaginal estrogens or vaginal moisturizer in breast cancer
survivors with urogenital atrophy: a preliminary study.
Biglia N, Peano E, Sgandurra
P, Moggio G, Panuccio E, Migliardi M, Ravarino N, Ponzone R, Sismondi P.
Department of Oncological
Gynaecology, University of Turin, Institute for Cancer Research and Treatment
of Candiolo (IRCC), Turin, Italy.
The study aim is to evaluate
the efficacy and safety of two low-dose vaginal estrogen treatments (ETs) and
of a non-hormonal vaginal moisturizer in postmenopausal breast cancer survivors
with urogenital atrophy. Eighteen patients receiving estriol cream 0.25 mg (n =
10) or estradiol tablets 12.5 mug (n = 8) twice/week for 12 weeks were evaluated
and compared with eight patients treated with polycarbophil-based moisturizer
2.5 g twice/week. Severity of vaginal atrophy was assessed using subjective
[Vaginal Symptoms Score (VSS), Profile of Female Sexual Function (PFSF)] and
objective [Vaginal Health Index (VHI), Karyopycnotic Index (KI)] evaluations,
while safety by measuring endometrial thickness and serum sex hormones levels.
After 4 weeks, VSS and VHI were significantly improved by both vaginal ETs,
with further improvement after 12 weeks. PFSF improved significantly only in
estriol group (p = 0.02). Safety measurements did not significantly change.
Vaginal moisturizer improved VSS at week 4 (p = 0.01), but score returned to
pre-treatment values at week 12; no significant modification of VHI, KI, PFSF
was recorded. Both low-dose vaginal ET are effective for relieving urogenital
atrophy, while non-hormonal moisturizer only provides transient benefit. The
increase of serum estrogens levels during treatment with vaginal estrogen at
these dosages is minimal.
Int J Cardiol. 2010 Feb 26. [Epub ahead of print]
Serum calcium, phosphorus and cardiovascular events in post-menopausal
women.
Slinin Y, Blackwell T, Ishani
A, Cummings SR, Ensrud KE; for the MORE Investigators.
Center for Chronic Disease
Outcomes Research, VA Medical Center, Minneapolis, MN, United States;
Department of Medicine, University of Minnesota, Minneapolis, MN, United
States.
BACKGROUND: There is
increasing evidence linking phosphorus and calcium levels to a higher risk of
cardiovascular morbidity and mortality in the general population. METHODS: We
performed a post hoc data analysis from the Multiple Outcomes of Raloxifene
Evaluation (MORE) trial of raloxifene treatment in 7259 postmenopausal women
with osteoporosis to test the hypothesis that higher baseline calcium and
phosphorus levels are associated with a higher risk of incident cardiovascular
events during 4years of follow-up. RESULTS: Baseline mean (SD) values were 2.3
(0.1)mmol/L for serum calcium, 1.2 (0.2)mmol/L for serum phosphorus. Adjusted
for multiple covariates including 25(OH)D, parathyroid hormone, and phosphorus,
adjusted hazard ratios (AHR) (95% confidence interval (CI)) per SD of calcium
were: 1.17(1.01-1.35), p=0.03 for combined cardiovascular outcome,
1.22(0.99-1.49), p=0.06 for cerebrovascular events, 1.12(0.92-1.37), p=0.25 for
coronary heart disease, and 1.18(0.94-1.48), p=0.16 for death. While there was
some evidence that higher serum phosphorus levels were associated with higher
rate of combined cardiovascular outcome (p=0.07) and cerebrovascular events
(p=0.03) in pauci-variable analysis, these associations did not persist after
adjustment for additional confounders. Adjusted for multiple covariates
including 25(OH)D, parathyroid hormone, and calcium, AHR(95% CI) per SD of
phosphorus were 0.88(0.77-1.01), p=0.07 for combined cardiovascular outcome,
0.86(0.70-1.06), p=0.15 for ceverbrovascular events, 0.92(0.76-1.10), p=0.35
for coronary heart disease, and 1.00(0.80-1.25) for death. CONCLUSION: We found
an independent association between higher baseline serum calcium levels and
higher rate of cardiovascular events. Our findings did not support an
independent association between serum phosphorus levels and cardiovascular
events.
Clin Oncol (R Coll Radiol). 2010 Feb 25. [Epub ahead of print]
Metabolic Syndrome, Central Obesity and Insulin Resistance are
Associated with Adverse Pathological Features in Postmenopausal Breast Cancer.
Healy LA, Ryan AM, Carroll P,
Ennis D, Crowley V, Boyle T, Kennedy MJ, Connolly E, Reynolds JV.
Department of Clinical
Nutrition, St James's Hospital and Trinity College Dublin, Ireland.
AIMS: Obesity is associated
with both an increased risk of postmenopausal breast cancer and increased mortality
rates. The mechanism is unclear, and central (visceral) obesity, insulin
resistance, altered sex steroids and altered adipokines are mooted as possible
factors. These features may cluster in the so-called metabolic syndrome. The
relevance of metabolic syndrome to the biology of breast cancer is unknown, and
this was the focus of the present study. MATERIALS AND METHODS: All
postmenopausal women with newly diagnosed breast cancer (n=105) were recruited.
A detailed clinical history was carried out, as well as a body composition
analysis, metabolic screen and measurement of adipokines and inflammatory
markers. RESULTS: The median age was 68 years (40-94 years) and the mean body
mass index was 28.3+/-5.2kg/m(2), with 87% of patients centrally obese. Metabolic
syndrome was diagnosed in 39% of patients, and was significantly associated
with central obesity (P<0.005) and increased inflammation, with C-reactive
protein levels doubling in metabolic syndrome patients compared with
non-metabolic syndrome patients (10.3 vs 5.8mg/l; P=0.084). Patients with a
later pathological stage (II-IV) were significantly more likely to be obese
(P=0.007), centrally obese (P=0.009), hyperglycaemic (P=0.047) and
hyperinsulinaemic (P=0.026); 51% had metabolic syndrome compared with 12% for
early stage disease. Patients with node-positive disease were significantly
more likely to be hyperinsulaemic (P=0.030) and have metabolic syndrome
(P=0.028) than patients with node-negative disease. DISCUSSION: The data
suggest that metabolic syndrome and central obesity are common in
postmenopausal breast cancer patients, and that metabolic syndrome may be
associated with a more aggressive tumour biology.
Br J Cancer. 2010
Mar 2;102(5):799-802. Epub 2010 Feb 16.
Bisphosphonates for osteoporosis treatment are associated with reduced
breast cancer risk.
Newcomb PA, Trentham-Dietz A,
Hampton JM.
[1] University of Wisconsin
Paul P Carbone Comprehensive Cancer Center, 610 Walnut Street, Madison, WI
53726, USA [2] Cancer Prevention Program, Fred Hutchinson Cancer Research
Center, 1100 Fairview Ave N, M4-B402, PO Box 19024, Seattle, WA 98109, USA.
Background:Bisphosphanates are
used primarily for the prevention and treatment of osteoporosis, and are also
indicated for osseous complications of malignancy. In addition to their bone
resorption properties, the most commonly used nitrogen-containing
bisphosphonate compounds also inhibit protein prenylation, and thus may exert
anti-tumour properties.Methods:To evaluate whether the use of these drugs may be
associated with cancer, specifically breast cancer, we conducted a
population-based case-control study in Wisconsin from 2003 to 2006.
Participants included 2936 incident invasive breast cancer cases and 2975
population controls aged <70 years. Bisphosphonate use and potential
confounders were assessed by interview.Results:Using multivariable logistic
regression, the odds ratio for breast cancer in current bisphosphonate users
compared with non-users was 0.67 (95% confidence interval 0.51-0.89). Increasing
duration of use was associated with a greater reduction in risk (P-trend=0.01).
Risk reduction was observed in women who were not obese
(P-interaction=0.005).Conclusion:These results are suggestive of an additional
benefit of the common use of bisphosphonates, in this instance, the reduction
in breast cancer risk.
J Clin Endocrinol Metab. 2010 Mar;95(3):1174-81. Epub 2010 Jan 15.
Effect of osteoporosis treatment on mortality: a meta-analysis.
Bolland MJ, Grey AB, Gamble
GD, Reid IR.
Osteoporosis Research Group,
Department of Medicine, University of Auckland, Private Bag 92 019, Auckland,
New Zealand. m.bolland@auckland.ac.nz.
Context: Fragility fractures
cause significant morbidity and mortality. Effective osteoporosis treatment can
reduce fracture incidence, but it is not known whether it reduces mortality.
Objective: The aim of the study was to determine whether effective osteoporosis
treatment reduces mortality. Data Sources: We searched Medline and the Cochrane
Central Register of Trials prior to September 2008, as well as 2000-2008
American Society for Bone and Mineral Research conference abstracts. Study
Selection: Eligible studies were randomized placebo-controlled trials of
approved doses of medications with proven efficacy in preventing both vertebral
and nonvertebral fractures, in which the study duration was longer than 12
months and there were more than 10 deaths. Trials of estrogen and selective
estrogen receptor modulators were specifically excluded. Data Extraction: Data
were extracted from the text of the retrieved articles, published
meta-analyses, or the Food and Drug Administration web site. Data Synthesis:
Eight eligible studies of four agents (risedronate, strontium ranelate,
zoledronic acid, and denosumab) were included in the primary analysis. During
two alendronate studies, the treatment dose changed, and those studies were
only included in secondary analyses. In the primary analysis, treatment was
associated with an 11% reduction in mortality (relative risk, 0.89; 95%
confidence interval, 0.80-0.99; P = 0.036). In the secondary analysis, the
results were similar (relative risk, 0.90; 95% confidence interval, 0.81-1.0; P
= 0.044). Mortality reduction was not related to age or incidence of hip or
nonvertebral fracture, but was greatest in trials conducted in populations with
higher mortality rates. Conclusions: Treatments for osteoporosis with
established vertebral and nonvertebral fracture efficacy reduce mortality in
older, frailer individuals with osteoporosis who are at high risk of fracture.