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Steven R Cummings

Publications and source records attributed to Steven R Cummings.

At least 55 records · Page 3Linked to original sources
PubMed2005

Effect of raloxifene on prevention of dementia and cognitive impairment in older women: the Multiple Outcomes of Raloxifene Evaluation (MORE) randomized trial.

OBJECTIVE: This investigation examined whether raloxifene, a selective estrogen receptor modulator, affects the risk for Alzheimer's disease. METHOD: The Multiple Outcomes of Raloxifene Evaluation was a randomized, placebo-controlled trial among postmenopausal women with osteoporosis. The effect of raloxifene (60 or 120 mg/day) on vertebral fractures was the primary outcome. Development of mild cognitive impairment and dementia was a secondary outcome. Women were given clinical and cognitive evaluations at baseline and annually. After 3 years, among the 5,386 women enrolled at participating sites, those who had clinical symptoms of dementia or scored in the lowest 10th percentile on cognitive screening were evaluated by a blinded dementia specialist and had brain scans and laboratory tests to evaluate dementia etiology. Dementia was diagnosed by a blinded adjudication committee. RESULTS: Of the 5,386 women, 5,153 (95.7%) were classified as cognitively normal, 181 (3.4%) had mild cognitive impairment, and 52 (1.0%) had dementia, 36 with Alzheimer's disease. Compared to those taking placebo, women receiving 120 mg/day of raloxifene had a 33% lower risk of mild cognitive impairment (relative risk, 0.67; 95% confidence interval [CI], 0.46-0.98) and somewhat lower risks of Alzheimer's disease (relative risk=0.52, 95% CI=0.22-1.21) and any cognitive impairment (relative risk=0.73, 95% CI=0.53-1.01). Risks of mild cognitive impairment, Alzheimer's disease, and any impairment were not significantly different in the group taking 60 mg/day of raloxifene. CONCLUSIONS: Raloxifene at a dose of 120 mg/day, but not 60 mg/day, resulted in reduced risk of cognitive impairment in postmenopausal women.

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PubMed2004

Diabetes and bone loss at the hip in older black and white adults.

UNLABELLED: Type 2 diabetes may be associated with elevated fracture risk, but the impact on bone loss is unknown. Analysis of 4-year change in hip BMD data from a cohort of white and black well-functioning men and women 70-79 years of age found that white women with diabetes had more rapid bone loss at the femoral neck than those with normal glucose metabolism. INTRODUCTION: Type 2 diabetes may be associated with elevated fracture risk in older adults. Although type 2 diabetes is not associated with lower BMD, older diabetic adults have a higher prevalence of other risk factors for fracture, including more frequent falls, functional limitations, and diabetic complications. With this burden of risk factors, loss of BMD could place older adults with diabetes at higher risk of sustaining a fracture. MATERIALS AND METHODS: To determine if bone loss is increased with type 2 diabetes, we analyzed data from the Health, Aging, and Body Composition Study of white and black well-functioning men and women 70-79 years of age. Hip BMD was measured at baseline and 4 years later in 480 (23%) participants with diabetes, 439 with impaired glucose metabolism, and 1172 with normal glucose homeostasis (NG). RESULTS: Those with diabetes had higher baseline hip BMD and weight, but among white women, had more weight loss over 4 years. White women with diabetes lost more femoral neck and total hip BMD than those with NG in age-adjusted models. After multivariable adjustment, diabetes was associated with greater loss of femoral neck BMD (-0.32%/year; 95% CI: -0.61, -0.02) but not total hip BMD. In men and black women, change in hip BMD was similar for participants with diabetes and NG. CONCLUSIONS: Despite having higher baseline BMD, diabetic white women, but not men or black women, had more rapid bone loss at the femoral neck than those with NG. This increased bone loss may contribute to the higher fracture risk observed in older diabetic women.

Age Factors↗
PubMed2004

Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women.

UNLABELLED: We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants. There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures. INTRODUCTION: Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures, potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy. We prospectively tested this hypothesis in the Study of Osteoporotic Fractures (SOF). MATERIALS AND METHODS: We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline. Hip fracture analyses included 708 hip fractures; vertebral fracture analyses included 267 incident vertebral fractures. Baseline serum estradiol and free testosterone values were available in a small subset of participants. RESULTS AND CONCLUSION: There were no significant differences in age, weight, or BMD between the women who underwent postmenopausal oophorectomy (n = 583) and those who did not (n = 5712). Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy. A history of postmenopausal oophorectomy was not associated with an increased risk of hip (hazard ratio [HR] = 1.1; 95% CI = 0.9-1.5) or vertebral fracture (HR = 0.7; 95% CI = 0.5-1.2). The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level (HR = 1.3; 95% CI = 0.5-3.2) or serum free testosterone level (HR = 1.7; 95% CI = 0.8-3.7) to the model. In summary, postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort. These results are in contrast to previous findings, suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully elucidated and that incidental oophorectomy after menopause should still be considered carefully in each potential patient.

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PubMed2004

The genetics of human longevity.

Many of the genes that affect aging and longevity in model organisms, such as mice, fruit flies, and worms, have human homologs. This article reviews several genetic pathways that may extend lifespan through effects on aging, rather than through effects on diseases such as atherosclerosis or cancer. These include some of the genes involved in the regulation of DNA repair and nuclear structure, which cause the progeroid syndromes when mutated, as well as those that may affect telomere length, since shorter telomeres have been associated with shorter survival. Other potential longevity genes, such as sirtuins, are involved in regulating the response to cellular stress, including caloric restriction. The best-studied pathway involves insulin and insulin-like growth factor 1 signaling; mutations in homologs of these genes have extended lifespan up to sixfold in model organisms. Other potential candidates include mitochondrial DNA and the genes that regulate the inflammatory response. Despite the challenges in study design and analysis that face investigators in this area, the identification of genetic pathways that regulate longevity may suggest potential targets for therapy.

Aging↗
PubMed2004

Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene.

BACKGROUND: The randomized, double-blind Multiple Outcomes of Raloxifene Evaluation (MORE) trial found that 4 years of raloxifene therapy decreased the incidence of invasive breast cancer among postmenopausal women with osteoporosis by 72% compared with placebo. We conducted the Continuing Outcomes Relevant to Evista (CORE) trial to examine the effect of 4 additional years of raloxifene therapy on the incidence of invasive breast cancer in women in MORE who agreed to continue in CORE. METHODS: Women who had been randomly assigned to receive raloxifene (either 60 or 120 mg/day) in MORE were assigned to receive raloxifene (60 mg/day) in CORE (n = 3510), and women who had been assigned to receive placebo in MORE continued on placebo in CORE (n = 1703). Breast cancer incidence was analyzed by a log-rank test, and a Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: During the CORE trial, the 4-year incidences of invasive breast cancer and estrogen receptor (ER)-positive invasive breast cancer were reduced by 59% (HR = 0.41; 95% CI = 0.24 to 0.71) and 66% (HR = 0.34; 95% CI = 0.18 to 0.66), respectively, in the raloxifene group compared with the placebo group. There was no difference between the two groups in incidence of ER-negative invasive breast cancer during CORE (P = .86). Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% (HR = 0.34; 95% CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI = 0.15 to 0.40), respectively, in the raloxifene group compared with the placebo group. During the CORE trial, the relative risk of thromboembolism in the raloxifene group compared with that in the placebo group was 2.17 (95% CI = 0.83 to 5.70). This increased risk, also observed in the MORE trial, persisted over the 8 years of both trials. CONCLUSIONS: The reduction in invasive breast cancer incidence continues beyond 4 years of raloxifene treatment in postmenopausal women with osteoporosis. No new safety concerns related to raloxifene therapy were identified during CORE.

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PubMed2004

Risk factors for a first-incident radiographic vertebral fracture in women > or = 65 years of age: the study of osteoporotic fractures.

UNLABELLED: Vertebral fractures in older women signal an increased risk of additional osteoporotic fractures. To identify risk factors for first vertebral fractures, we studied 5822 women > or =65 years of age who had no fracture on baseline radiographs of the spine. Several modifiable risk factors increased an older woman's risk of developing a first vertebral fracture, and women with multiple risk factors and low BMD had the highest risk. Risk factors and low BMD should be useful to help focus efforts to prevent these fractures. INTRODUCTION: Vertebral fractures are a common cause of back pain and disability and signal an increased risk of additional osteoporotic fractures in older women. Little is known about the risk factors for the first occurrence of a vertebral fracture. MATERIALS AND METHODS: To identify risk factors for a first vertebral fracture, we studied 5822 women > or =65 years of age from the Study of Osteoporotic Fractures who had no fracture on baseline radiographs of the spine. We measured potential risk factors and BMD of the wrist and calcaneus at baseline and BMD of the spine and hip halfway through follow-up. Fractures were assessed by standard methods from spine radiographs obtained at baseline and follow-up an average of 3.7 years later. RESULTS AND CONCLUSIONS: In multivariable analyses, older age, previous nonspine fracture, low BMD at all sites, a low body mass index (BMI), current smoking, low milk consumption during pregnancy, low levels of daily physical activity, having a fall, and regular use of aluminum-containing antacids independently increased the risk of a first vertebral fracture. Women using estrogen and those who engaged in recreational physical activity had a decreased risk. The effects of low BMI, smoking, use of estrogen and antacids, and previous fracture were partially mediated by BMD. Women in the lower third of wrist BMD with five or more risk factors had a 12-fold greater risk than women in the highest third of BMD who had zero to three risk factors. The 27% of women at highest risk suffered 60% of the incident fractures. In conclusion, several modifiable risk factors and BMD independently increase an older woman's risk of developing a first vertebral fracture. The combination of risk factors and BMD should be useful for focusing efforts to prevent vertebral fractures.

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PubMed2004

Clinical utility of laboratory testing in women with osteoporosis.

Clinicians regularly order laboratory tests in women with osteoporosis to assess if an underlying medical condition is contributing to bone loss. To determine which laboratory tests are associated with osteoporosis we conducted a secondary analyses of data collected as part of the Fracture Intervention Trial (FIT), which included 15,316 postmenopausal women. Women had tests of liver and kidney function, mineral metabolism, electrolytes and complete blood count, femoral neck and total body BMD and spinal radiographs. The prevalence of abnormal tests in women with osteoporosis compared to women without was not different, except for low TSH (<0.5 IU/ml). Among women with and without osteoporosis at the femoral neck the prevalence of low TSH was 4.9% (95% CI: 4.4-5.5) and 3.7% (95% CI: 3.3-4.1), respectively, yielding a positive likelihood ratio of 1.2 (95% CI: 1.1-1.3). We observed similar results for women with vertebral fractures compared to women without vertebral fractures; positive likelihood ratio of 1.4 (95% CI: 1.3-1.6). Our data suggests that when assessing healthy women with osteoporosis ordering a routine panel of laboratory tests is not useful but measuring TSH may be informative.

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PubMed2004

Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial.

UNLABELLED: NO regulates bone remodeling in cellular and animal models. We examined the effect of administering ISMO, a NO donor, on bone turnover in 144 postmenopausal women. After 3 months, women randomized to ISMO had a greater decrease in bone resorption and a greater increase in bone formation compared with placebo. NO donors may prevent postmenopausal bone loss. INTRODUCTION: NO both stimulates bone formation and inhibits bone resorption in vitro. NO donors (nitrates) are inexpensive and widely available, but their value for postmenopausal osteoporosis has never been evaluated in a randomized trial. MATERIALS AND METHODS: We randomly assigned 144 healthy postmenopausal women with a hip BMD T score between 0 and -2.5 to 5 or 20 mg/day of isosorbide mononitrate (ISMO) or placebo for 12 weeks. We measured urine N-telopeptide (NTx), a marker of bone resorption, and serum bone-specific alkaline phosphatase (BSALP), a marker of bone formation. Markers were measured immediately before randomization and after 12 weeks of treatment. We calculated the percent change in NTx and BSALP for each of the treatment groups (placebo, 5 mg ISMO, and 20 mg ISMO). Our primary outcome was the percent change in NTx and BSALP in the 5- and 20-mg ISMO groups compared with placebo. RESULTS AND CONCLUSIONS: Compared with women randomized to placebo, women randomized to 20 mg of ISMO had a 45.4% decrease in NTx (95% CI, 25.8-64.9) and a 23.3% increase (95% CI, 8.9-37.8) in BSALP. Women randomized to 5 mg of ISMO had a 36.3% decrease in NTx (95% CI, 14.8-57.8) and a 15.9% increase in BSALP (95% CI, 1.1-30.7). ISMO decreases bone resorption and increases bone formation. These findings suggest that nitrates may be useful for the prevention of postmenopausal osteoporosis.

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PubMed2004

Association of the G-174C variant in the interleukin-6 promoter region with bone loss and fracture risk in older women.

UNLABELLED: We analyzed the association between the IL-6 G-174C polymorphism and osteoporosis phenotypes in 3376 older women. Women with the C/C genotype had a significantly slower rate of decline in hip BMD and a 33% lower risk of wrist fracture than women with the G/G genotype. Variation at the IL-6 locus may contribute to the genetic susceptibility to bone fragility. INTRODUCTION: Interleukin 6 (IL-6) promotes osteoclast formation and bone resorption. The C allele of the G-174C polymorphism in the IL-6 promoter region has been related to lower gene transcription and plasma IL-6 levels. MATERIALS AND METHODS: In this study, we evaluated the relationship between the IL-6 G-174C polymorphism and BMD, the rate of decline in BMD, and the risk of fracture in 3376 women 65 years of age and older participating in the Study of Osteoporotic Fractures. BMD was measured at the distal and proximal radius using single photon absorptiometry and at the hip using DXA. Hip BMD was measured again an average of 3.5 years later. Incident fractures over an average of 10.8 years of follow-up were confirmed by physician adjudication of radiology reports. RESULTS: Distal and proximal radius BMD was lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype (p = 0.016 and p = 0.049, respectively), although the differences between the genotypes were small. While there were no differences by genotype with initial hip BMD, women with the C/C genotype experienced a slower rate of decline in total hip and femoral neck BMD compared with women with the G/G genotype (p = 0.004 and p = 0.029, respectively). Women with the C/C genotype also had 33% lower risk of wrist fracture compared with women with the G/G genotype, independent of age, body mass index, estrogen use, and study center (RR, 0.67; 95% CI, 0.45, 1.00; p = 0.048), whereas heterozygous women had a more intermediate risk (RR, 0.85; 95% CI, 0.65, 1.12; p = 0.256). No association was found between genotype and risk of hip or all non-spine fractures. CONCLUSIONS: These results suggest that the IL-6 G-174C promoter polymorphism may be a genetic marker for bone loss and wrist fracture among older women.

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PubMed2004

Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment.

BACKGROUND: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life. OBJECTIVE: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men. METHODS: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men. The search terms included fractures, bone density, or osteoporosis plus either epidemiology, diagnosis, prevention, control, or therapy. Additional search terms included specific subtopics (eg, bisphosphonates, calcium, exercise, parathyroid hormone). The authors contributed additional relevant publications. RESULTS: Morbidity after fragility fracture is at least as high in men as in women, and the rate of fracture-related mortality 1 year hip fracture is approximately double in men compared with women. The bioavailable fraction of testosterone slowly declines into the ninth decade in men. There is evidence that the effect of estrogen on bone is greater than that of testosterone in men. Diagnosing osteoporosis in men is complicated by a lack of consensus on how it should be defined. Significant risk factors for osteoporosis or fracture include low bone mineral density, previous fragility fracture, maternal history of fracture, marked hypogonadism, smoking, heavy alcohol intake or alcoholism, low calcium intake, low body mass or body mass index, low physical activity, use of bone-resorbing medication such as glucocorticoids, and the presence of such conditions as hyperthyroidism, hyperparathyroidism, and hypercalciuria. Prevention is paramount and should begin in childhood. During adulthood, calcium (1000-1500 mg/d), vitamin D (400-800 IU/d), and adequate physical activity play crucial preventive roles. When treatment is indicated, the bisphosphonates are the first choice, whereas there is less support for the use of calcitonin or androgen therapy. Parathyroid hormone (1-34) is a promising anabolic therapy. There is also strong evidence for the use of bisphosphonates for the treatment of glucocorticoid-induced osteoporosis.

Androgens↗
PubMed2004

Effect of raloxifene on urinary incontinence: a randomized controlled trial.

OBJECTIVE: To estimate the effect of 3 years of treatment with raloxifene on urinary incontinence in postmenopausal women. METHODS: We used measures of urinary incontinence severity, frequency, and type in the Multiple Outcomes of Raloxifene trial, a multicenter randomized, controlled trial of women who were at least 2 years postmenopausal with osteoporosis. At 10 U.S. sites of this trial, 963 women randomly assigned to raloxifene or placebo completed questionnaires about incontinence at baseline and 3 years later. We analyzed the odds of worsening severity and frequency of incontinence and type of incontinence after 3 years of treatment with raloxifene. RESULTS: The mean age of our subjects was 68.3 +/- 7 years. After 3 years of treatment, there was no significant difference between raloxifene and placebo groups in urinary incontinence severity (multivariable odds ratio [OR] 1.02; 95% [CI] 0.78, 1.34). The majority of the women (60%) had no change in urinary incontinence episodes from baseline to year 3. The odds of worsening urinary incontinence severity after 3 years of raloxifene treatment were 1.05 (95% CI 0.75, 1.48). Similarly, the odds of developing new onset incontinence were 0.95 (95% CI 0.59, 1.52). Finally, raloxifene did not effect the odds of having stress (OR 1.01; 95% CI 0.71, 1.43) or urge (OR 1.20; 95% CI 0.86, 1.68) incontinence after 3 years of use. CONCLUSION: In postmenopausal women with osteoporosis, 3 years of treatment with raloxifene had no effect on urinary incontinence. LEVEL OF EVIDENCE: I

Administration, Oral↗
PubMed2004

Effects of ultralow-dose transdermal estradiol on bone mineral density: a randomized clinical trial.

OBJECTIVE: Because small increments in levels of endogenous plasma estradiol are associated with higher postmenopausal bone mineral density, we investigated the safety and effectiveness in preventing bone loss of unopposed, very-low-dose transdermal estradiol for postmenopausal women. METHODS: This was a randomized, placebo-controlled, double-blind trial with 2-year follow-up at 9 United States clinical centers. The study population comprised 417 postmenopausal women, aged 60-80 years, with intact uterus and bone mineral density z scores of -2.0 or higher, who were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). All participants received calcium and vitamin D supplementation. Lumbar spine and total hip bone mineral density change was measured by dual-energy X-ray absorptiometry; endometrial hyperplasia incidence was assessed by endometrial biopsy. RESULTS: Median plasma estradiol level in the estradiol group increased from 4.8 pg/mL at baseline to 8.5 pg/mL at 1 year (P <.001 versus baseline) and to 8.6 pg/mL at 2 years (P <.001 versus baseline) and was unchanged in the placebo group. Lumbar spine bone mineral density increased 2.6% in the estradiol group and 0.6% in the placebo group (between-group difference 2.0%, P <.001). Mean total hip bone mineral density increased 0.4% in the estradiol group and decreased 0.8% in the placebo group (between-group difference 1.2%, P <.001). Osteocalcin levels and bone-specific alkaline phosphatase were lower in the estradiol group than the placebo group (P <.001 each). Endometrial hyperplasia developed in 1 woman in the estradiol group but in none of the placebo group (difference in 2-year rates 0.5%, 95% confidence interval 0-7.3%). CONCLUSION: Postmenopausal treatment with low-dose, unopposed estradiol increased bone mineral density and decreased markers of bone turnover without causing endometrial hyperplasia.

Administration, Cutaneous↗
PubMed2004

Long-term prediction of incident hip fracture risk in elderly white women: study of osteoporotic fractures.

OBJECTIVES: To identify independent risk factors for first hip fracture over 10 years of follow-up. DESIGN: Prospective cohort study. SETTING: Four U.S. clinical centers. PARTICIPANTS: A total of 6,787 women aged 66 and older in the Study of Osteoporotic Fractures. MEASUREMENTS: Total hip bone mineral density (BMD) using dual-energy x-ray absorptiometry and a comprehensive set of potential risk factors were collected. Incident hip fractures were identified prospectively and confirmed using radiographic report. RESULTS: Six hundred two women (8.9%) had a hip fracture during a mean +/- standard deviation (SD) follow-up of 10.1 +/- 3.2 years. Older age, previous self-reported fracture after age 50, maternal history of hip fracture after age 50, greater height at age 25, impaired cognition, slower walking speed, nulliparity, type II diabetes mellitus, Parkinson's disease, and depth perception each independently predicted a 1.17- to 1.83-fold increase in hip fracture risk, whereas each SD (0.13 g/cm2) decrease in hip BMD was independently associated with a 1.84-fold increase in risk. Lower body mass index also was associated with an increased risk of hip fracture, although lower hip BMD largely explained this association. CONCLUSION: Although hip BMD is strongly related to hip fracture risk in elderly white women, other clinical risk factors also are independent predictors of long-term risk and provide additional insight into the prevention of fracture in high-risk women. Clinicians should be alert to factors other than BMD that place older women at a high risk of hip fracture.

Absorptiometry, Photon↗
PubMed2004

Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study.

The purpose of this study was to test whether low serum vitamin B-12 levels are associated with more rapid bone loss in elderly women. We archived sera and measured calcaneal bone mineral density (BMD) in community-dwelling white women, aged 65 yr and over, who participated in the Study of Osteoporotic Fractures. BMD of the hip and subregions was measured 2 yr later. Repeat measurements of calcaneal and hip BMD were obtained after 5.9 and 3.5 yr of follow-up, respectively. Serum vitamin B-12 assays were performed in 83 randomly selected participants with initial and repeat measurements of BMD who were not taking estrogen replacement therapy at baseline. After adjusting for age, weight, and clinic site, women with vitamin B-12 levels at or below 280 pg/ml (207.2 pmol/liter; lowest quintile) experienced an annual change of -1.6% (95% confidence interval, -2.4% to -0.8%) in total hip BMD, compared with -0.2% (-0.5% to 0.2%) in women with levels above 280 pg/ml (P = 0.003). Results were similar when subregions of the hip were analyzed separately. Serum vitamin B-12 levels were not significantly associated with calcaneal bone loss. We conclude that low serum vitamin B-12 levels are associated with increased rates of hip, but not calcaneal, bone loss in older women.

Aged↗
PubMed2004

Adipocytokines attenuate the association between visceral adiposity and diabetes in older adults.

OBJECTIVE: To examine whether adiponectin is independently associated with diabetes and whether adiponectin and other adipocytokines account for the relationship between fat and diabetes. RESEARCH DESIGN AND METHODS: A nested case-control study from the Health, Aging, and Body Composition (Health ABC) study. We measured four adipocytokines: adiponectin, interleukin (IL)-6, tumor necrosis factor-alpha, and plasminogen activator inhibitor 1 (PAI-1). Regional fat area was determined by computed tomography scan. The 519 case subjects had diabetes defined by fasting plasma glucose level > or =126 mg/dl or by use of diabetes medications. The 519 control subjects had normal glucose tolerance and were matched by sex, race, and study site. Sex-specific logistic models were adjusted for age, race, site, total adiposity, smoking, and physical activity. RESULTS: Higher adiponectin levels were associated with lower risk of diabetes (P < 0.001). Visceral fat was the only adiposity measure associated with diabetes after adjusting for BMI (odds ratio 3.0 [2.1-4.3] in women and 1.3 [1.0-1.6] in men, P < 0.001 between-sex comparison). Adipocytokines attenuated the association between visceral fat and diabetes for both sexes but more strongly in men (women 2.3 [1.5-3.3], men 1.1 [0.9-1.4]). In men, adiponectin, IL-6, and PAI-1 remained independently associated with diabetes after adjusting for fat depots; in women, adiponectin was the only independently associated adipocytokine. Controlling for insulin, HDL, triglycerides, and blood pressure did not change these results. CONCLUSIONS: Adiponectin is associated with lower odds of diabetes in older men and women. Whereas several adipocytokines explained the relationship between visceral adiposity and diabetes in men, only adiponectin partially mediated this association among women.

Adiponectin↗
PubMed2003

Association of nitrate use with risk of new radiographic features of hip osteoarthritis in elderly white women: the study of osteoporotic fractures.

OBJECTIVE: To examine the association between nitrate medication use and the development of new radiographic findings of hip osteoarthritis (OA) in elderly women. METHODS: Pelvic radiographs were obtained at baseline and a mean of 8.3 years later in 5,987 women, age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. Atlas-standardized individual radiographic features (IRFs) of OA were assessed and minimal joint space was measured on paired films. New radiographic findings of hip OA were defined as the development in hips free of these findings at baseline: 1) joint space narrowing (JSN), which consisted of either a MJS < or =1.5 mm or an IRF score indicating lateral JSN > or =2 or medial JSN > or =3; 2) an IRF score for osteophytes of > or =2 in any location; or 3) a summary grade of 2 or more (at least 2 IRFs present). Nitrate use was recorded by interview at years 6 and 8. Logistic and linear regression analyses were performed to determine the association of nitrate use with new radiographic findings of hip OA, adjusting for age, weight, height, bone mineral density, and estrogen. RESULTS: Compared with no reported use of nitrates, we found significant associations between use of nitrates at 1 clinic visit and new JSN (odds ratio [OR] 1.94, 95% confidence interval [95% CI] 1.18-3.17, P = 0.009), new osteophyte formation (OR 1.70, 95% CI 1.03-2.88, P = 0.04), and any new radiographic finding of hip OA or total hip arthroplasty for OA (OR 1.71, 95% CI 1.16-2.52, P = 0.007). Any nitrate use was associated with an increased risk of developing summary grade 3 or greater hip OA (OR 1.84, 95% CI 1.03-3.31, P = 0.041), but not with any other incident findings of OA. CONCLUSION: Older women using nitrates may have an increased risk of developing new radiographic findings of hip OA.

Aged↗
PubMed2003

Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial.

CONTEXT: In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures. OBJECTIVE: To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years. INTERVENTION: Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOME MEASURES: All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk. RESULTS: Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54). CONCLUSIONS: This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.

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