Association between African American race/ethnicity and low bone mineral density in women with systemic lupus erythematosus

OBJECTIVE: To determine the association between race/ethnicity and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE). METHODS: Women with SLE (n = 298), including 77 African Americans and 221 whites, completed this cross-sectional study conducted from 1996 to 2002. Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. Study participants completed a self-administered questionnaire and a physician completed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). BMD results were expressed as Z scores. Analyses were performed to identify factors, including race/ethnicity, associated with low BMD defined as a Z score -1.0 or less at the hip or lumbar spine. RESULTS: African Americans compared with whites were younger at study visit (mean +/- SD 39.7 +/- 8.4 years versus 42.9 +/- 11.6 years) and had higher SDI (mean +/- SD 1.8 +/- 2.0 versus 1.0 +/- 1.6), but similar proportions of women were postmenopausal (31.2% versus 38.0%). African Americans had significantly lower mean BMD Z scores at the hip (-0.49 versus -0.07; group difference -0.41; 95% confidence interval [95% CI] -0.70, -0.13) and at the lumbar spine (-1.03 versus 0.10; group difference -1.13; 95% CI -1.48, -0.78) compared with whites. African American race/ethnicity was strongly associated with low BMD at the lumbar spine (adjusted odds ratio 4.42; 95% CI 2.19, 8.91) but not at the hip, adjusting for factors associated with low BMD. CONCLUSION: African American women compared with white women with SLE had lower BMD at the hip and lumbar spine. African American race/ethnicity was associated with low BMD at the lumbar spine controlling for relevant clinical covariates.     

Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial

BACKGROUND: Many women using hormone replacement therapy (HRT) will discontinue HRT and lose its bone-protective effect. Methods to preserve bone density in these women need to be explored. This multicenter, international, randomized, blinded, 12-month study was conducted to assess the effect of alendronate sodium on bone density in women who had recently discontinued HRT. METHODS: The 144 postmenopausal women included in the study were diagnosed as having low bone mineral density (BMD) and had recently discontinued HRT. They were randomized to receive either a daily dose of 10 mg of alendronate sodium or matching placebo. The main outcome measures were spine, hip, and total body BMD; biochemical markers of bone turnover; and tolerability. RESULTS: Alendronate treatment was associated with a 2.3% mean increase (95% confidence interval [CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2% (95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and placebo. Greater hip and total body BMD preservation was also observed with alendronate use. Bone turnover decreased significantly with alendronate (bone-specific alkaline phosphatase levels decreased by 20% and urinary N-telopeptide/creatinine ratio by 47%), but increased in the placebo group (by 18% and 36%, respectively). Alendronate was well tolerated, with no increase in adverse events compared with placebo. CONCLUSIONS: A high rate of bone loss was observed in the first 12 to 15 months after discontinuation of HRT in postmenopausal women with low BMD. Treatment with alendronate increased or maintained both spine and hip BMD and prevented the increase in bone resorption seen with withdrawal of HRT in this population.     

Incidence of diabetes among postmenopausal breast cancer survivors

Aims/hypothesis

Evidence is emerging of an association between breast cancer and diabetes; however, it is uncertain whether diabetes incidence is increased in postmenopausal breast cancer survivors compared with women without breast cancer. The objective of this study was to determine whether postmenopausal women who develop breast cancer have a higher incidence of diabetes than those who do not develop breast cancer.

Methods

We used population-based data from Ontario, Canada to compare the incidence of diabetes among women with breast cancer, aged 55 years or older, from 1996 to 2008, with that of age-matched women without breast cancer. We used Cox proportional hazard models to estimate the effect of breast cancer on the cause-specific hazard of developing diabetes overall and in the subgroup of women who received adjuvant chemotherapy.

Results

Of 24,976 breast cancer survivors and 124,880 controls, 9.7% developed diabetes over a mean follow-up of 5.8 years. The risk of diabetes among breast cancer survivors compared with women without breast cancer began to increase 2 years after diagnosis (HR 1.07 [95% CI, 1.02, 1.12]), and rose to an HR of 1.21 (95% CI, 1.09, 1.35) after 10 years. Among those who received adjuvant chemotherapy (n?=?4,404), risk was highest in the first 2 years after diagnosis (HR 1.24 [95% CI 1.12, 1.38]) and then declined.

Conclusions/interpretation

We found a modest increase in the incidence of diabetes among postmenopausal breast cancer survivors that varied over time. In most women the risk began to increase 2 years after cancer diagnosis but the highest risk was in the first 2 years in those who received adjuvant therapy. Our study suggests that greater diabetes screening and prevention strategies among breast cancer survivors may be warranted.     

Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study

CONTEXT: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. OBJECTIVE: The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density. DESIGN, SETTING, AND PARTICIPANTS: Women with clinically diagnosed type 2 diabetes at baseline in the Women's Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. MAIN OUTCOME MEASURES: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured. RESULTS: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls [adjusted relative risk (RR) 1.20, 95% confidence interval (CI) 1.11-1.30]. In a subsample of women with baseline BMD scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone) among black women (RR 1.33, 95% CI 1.00-1.75) and women with increased baseline bone density (RR 1.26, 95% CI 0.96-1.66). CONCLUSION: Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).     

Effectiveness of adjuvant chemotherapy for node-positive operable breast cancer in older women

BACKGROUND: Randomized clinical trials have shown the efficacy of adjuvant chemotherapy in treating node-positive operable breast cancer in women aged < or = 69 years, but the benefit of chemotherapy in women aged > or = 70 is questionable. This study was to examine if adjuvant chemotherapy is effective for these women with breast cancer. METHODS: We studied a cohort of 5464 women diagnosed with node-positive operable breast cancer at age > or = 65 in 1992 through 1996 with last follow-up of December 31, 1999 in five states and six metropolitan areas. Hazard ratio (HR) for all-cause mortality was used for survival analysis with adjustment for patient and tumor characteristics; propensity analysis was used to control for observed factors; and sensitivity analysis was used to estimate potential effects of unmeasured confounders. RESULTS: After adjusting for propensity to receive chemotherapy, the chemotherapy-treated and untreated groups were not statistically significantly different for covariates except for age and hormone receptor status. Mortality was significantly reduced in women aged 65-69 who received adjuvant chemotherapy compared to those who did not, after adjusting for patient and tumor characteristics (HR = 0.70, 95% confidence interval [CI], 0.57-0.88) or after adjusting for propensity scores (HR = 0.76, 95% CI, 0.62-0.94). HR did not significantly differ between the treated and untreated women aged > or = 70 (HR = 0.96, 95% CI = 0.83-1.09, and HR = 0.99, 95% CI, 0.87-1.14). These results were relatively insensitive to changes in unmeasured confounders. CONCLUSIONS: Adjuvant chemotherapy is associated with improved survival in women with node-positive operable breast cancer aged 65-69 living in the community, but not in women aged > or = 70. These findings are consistent with those found in randomized controlled trials.     

Prevention of bone loss in survivors of breast cancer: A randomized, double-blind, placebo-controlled clinical trial

BACKGROUND: Few data are available on the safety and efficacy of once-weekly oral bisphosphonate therapy in breast cancer survivors. OBJECTIVE: Our objective was to determine whether risedronate, 35 mg weekly, is efficacious and safe in preventing bone loss associated with chemotherapy-induced menopause. DESIGN: The study was a randomized, double-blind, placebo-controlled clinical trial over 12 months. SETTING AND PARTICIPANTS: Participants included 87 newly postmenopausal women with status post chemotherapy, recruited from a breast cancer clinic in an academic medical center. INTERVENTION: Participants were randomly assigned to receive risedronate 35 mg/wk or placebo. MAIN OUTCOME MEASURES: The primary outcomes were the 12-month changes in spine and hip bone mineral density. Secondary outcomes included changes in markers of bone resorption (urine N-telopeptide cross-linked collagen type I) and formation (osteocalcin, N-terminal propeptide of type I procollagen, and bone-specific alkaline phosphatase). RESULTS: After 12 months, bone mineral density increased by 1.2% at the spine and 1.3% at the hip in women on risedronate vs. significant decreases for women in the placebo group of 0.9% at the spine and 0.8% at the hip (P < 0.01, difference between groups). N-telopeptide cross-linked collagen type I, a marker of bone resorption, decreased by 19.3%, and N-terminal propeptide of type I procollagen, a marker of bone formation, decreased by 26.6% in participants on active therapy compared with increases in the control group. Risedronate was well tolerated, and the retention rate was 95% at 1 yr. CONCLUSIONS: Risedronate once weekly prevented bone loss and reduced bone turnover in women with breast cancer treated with chemotherapy. Early measures to prevent bone loss should be considered in this cohort of breast cancer survivors.     

Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study

BACKGROUND: Breast cancer and its treatment may compromise bone health. We tested the hypothesis in the Women's Health Initiative Observational Study that postmenopausal survivors of breast cancer have a higher risk for fractures compared with women who have no cancer history. METHODS: A prospective cohort (5.1 years' follow-up) study design was used. Breast cancer survivors were women who reported a history of breast cancer (n = 5298). A reference group included women who had no cancer history at baseline (n = 80 848). Fracture occurrence was ascertained from annual self-reports. Hip fractures were confirmed by reviewing medical records. RESULTS: After adjustment for age, weight, ethnicity, and geographic region of enrollment, the hazard ratios (HRs) of breast cancer survivors to women in the reference group were 0.93 (95% confidence interval [CI], 0.64-1.33) for hip; 1.36 (95% CI, 1.16-1.59) for forearm or wrist; 1.31 (95% CI, 1.19-1.43) for eligible fractures other than hip, vertebral, and forearm or wrist; and 1.31 (95% CI, 1.21-1.41) for these fractures combined. The increased risk for clinical vertebral fracture was statistically significant only among survivors who had a breast cancer diagnosis before age 55 years (HR, 1.78; 95% CI, 1.28-2.46). After adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle, the increased risk for all fractures studied among survivors was reduced to 15% (HR, 1.15; 95% CI, 1.05-1.25). CONCLUSIONS: Postmenopausal survivors of breast cancer are at increased risk for clinical fractures. Preventions and therapeutic interventions are needed to reduce fracture risk in this large and growing population.     

Pamidronate in the prevention of chemotherapy-induced bone loss in premenopausal women with breast cancer: a randomized controlled trial

PURPOSE: Mortality from breast cancer has decreased in large part because of adjuvant chemotherapy. Sequelae of therapy include ovarian failure and bone loss, loss that would increase these patients' risk of fracture with aging. In this study, we assessed the efficacy of pamidronate in preventing such loss. PATIENTS AND METHODS: The study was a 1-yr randomized, double-blind, placebo-controlled trial comparing pamidronate 60 mg iv every 3 months with placebo in 40 premenopausal women with newly diagnosed breast cancer. Bone mineral density (BMD) of the spine and hip and remodeling markers were monitored over 1 yr. RESULTS: Over half of the subjects became amenorrheic, and those who did were 4 yr older than those who did not (P = 0.02). The mean difference in percent change in BMD at 12 months between the two treatment groups was 5.1% at the lumbar spine (P = 0.002) in the overall study group and 5% at the lumbar spine and 5.2% at the total hip in the amenorrheic subgroup (P < 0.03). Biochemical markers of bone remodeling did not differ between the two treatment groups, and treatment was well tolerated. CONCLUSION: Chemotherapy-induced amenorrhea is common with ensuing bone loss at the spine and hip. Pamidronate prevented bone loss at the spine and hip and was well tolerated.     

Risk of Dementia in Older Breast Cancer Survivors: A Population-Based Cohort Study of the Association with Adjuvant Chemotherapy

OBJECTIVES: To assess whether there is an association between delivery of adjuvant chemotherapy to older women with breast cancer and development of dementia over time.
DESIGN: Retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare claims data.
SETTING: Women residing in geographic areas included in the SEER registry.
PARTICIPANTS: Women aged 66 to 80 diagnosed with non-metastatic invasive breast cancer from 1992 to 1999 were included. It was determined whether patients had undergone chemotherapy within 6 months of diagnosis.
MEASUREMENTS: Whether women developed dementia over time was determined using diagnostic codes. The effect of adjuvant chemotherapy on development of dementia was evaluated, adjusting for confounders using a proportional hazards model stratified for age.
RESULTS: Twenty-one thousand three hundred sixty-two women met selection criteria; 2,913 received chemotherapy, and 18,449 did not. Women who received chemotherapy were younger than those who did not (median aged 70 vs 73; P <.001). Median follow-up time was 59 months. After controlling for other factors, it was found that chemotherapy was not associated with a greater risk of development of dementia over time for any age group (hazard ratio for dementia in women receiving chemotherapy: aged 66–70=0.83, 95% confidence interval (CI)=0.48–1.45, P =.5; aged 71–75=0.74, 95% CI=0.46–1.18, P =.2; aged 76–80=0.49, 95% CI=0.28–0.88, P =.02).
CONCLUSION: Receipt of chemotherapy in older women with breast cancer was not associated with a greater risk of dementia diagnosis over time; very elderly women who undergo chemotherapy may be at lower baseline risk. The use of a claims-based definition of dementia limited the study.     

The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women

Objective. To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids. Methods. One hundred ninety-five postmenopausal patients with RA were compared with 597 postmenopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x-ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex-users (18%). Results. Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4–10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0–13.0%) and by 7.4% at the hip (95% CI 1.2–13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex-user and never user groups. Results were confirmed in 54 patients who had whole-body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = –0.23, P < 0.01; whole-body BMD r = –0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = –0.32, P < 0.01; whole-body BMD r = –0.72, P < 0.01). Conclusion. Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low-dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.     

Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group

OBJECTIVE: To evaluate a single cycle of adjuvant chemotherapy compared with longer duration chemotherapy for premenopausal women or chemoendocrine therapy for postmenopausal women with operable breast cancer using a quality-of-life-oriented end point, Q-TWiST (quality-adjusted analysis of TWiST: Time Without Symptoms and Toxicity). DESIGN: Multicenter randomized clinical trial--International Breast Cancer Study Group (IBCSG: formerly Ludwig Group) Trial V. SETTING: IBCSG participating centers in Sweden, Switzerland, Australia, Yugoslavia, Spain, New Zealand, Italy, Germany, and South Africa. PATIENTS: Data were available for 1229 eligible patients with node-positive breast cancer who were randomized to receive one of three adjuvant treatments after at least a total mastectomy and axillary clearance. INTERVENTIONS: Patients received either a single cycle of perioperative chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and leucovorin; or six cycles (6 months) of a conventionally timed chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and prednisone for premenopausal women or this combination plus tamoxifen for postmenopausal women; or both perioperative and conventionally timed chemotherapy for a 7-month course of adjuvant therapy. RESULTS: At 5 years of median follow-up, patients who received the longer duration therapies had an improved 5-year disease-free survival percentage (53% compared with 36%; P less than 0.001) and 5-year overall survival percentage (73% compared with 63%; P = 0.001) compared with those who received the single perioperative cycle alone. By 3.5 years, the greater burden of toxic effects associated with the longer duration treatments was balanced by their superior control of disease. Within 5 years of follow-up, even after subtracting time with adjuvant treatment toxicity, patients gained an average of 2.2 months of Q-TWiST if treated with the longer duration therapies compared with the single cycle (P = 0.03). The gain for premenopausal patients was 2.8 months (P = 0.05), whereas the gain for postmenopausal women was 1.5 months (P greater than 0.2). CONCLUSIONS: Six or seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the quantity and quality of life for patients with node-positive breast cancer compared with a single short course of perioperative combination chemotherapy.     

Selective estrogen-receptor modulators

Tamoxifen is useful for adjuvant treatment of breast cancer and in some women for the prevention of breast cancer. The risk-benefit ratio in regard to the skeleton and perhaps other organ systems may very well be different for postmenopausal versus premenopausal women. In postmenopausal women, tamoxifen (20 mg/d) increased BMD in the spine and perhaps the hip; however, the effect on fracture risk is unclear. Therefore, for postmenopausal women with osteoporosis, consideration should be given to the addition of an agent that is shown to have efficacy against fractures (such as bisphosphonates), even while these women are on tamoxifen. For women at only modest or moderate risk, with bone density above the osteoporosis range (T score above -2.5) and no major fracture history, tamoxifen is probably adequate for 5 years of use. Potentially serious adverse effects include venous thromboembolism, uterine cancer, benign uterine disease, and cataracts. Raloxifene (60 mg/d) protects against vertebral fractures over 4 years in women with osteoporosis, produces small increases in bone mass of the spine, hip, and total body, and reduces bone turnover in postmenopausal women with or without osteoporosis. No significant effect has yet been demonstrated on nonvertebral fractures after 4 years of treatment. Raloxifene has the additional benefit of substantially reducing the risk of ER-positive invasive breast cancer and does not increase the risk of uterine disease. Raloxifene increases the risk of venous thromboembolic disease to the same degree as tamoxifen and estrogen. Therefore, SERMS and estrogens are generally contraindicated in women with a previous history of venous thromboembolism or those who are at significantly increased risk. Raloxifene is probably most useful in women who have osteoporosis (T score = -2.5) or who are at risk (T score less than -1.5 with clinical risk factors) in the middle menopausal period (age 55-65) or in the early menopausal period in women who have no significant hot flashes. At this stage in life, vertebral fractures are common, but hip fractures are not. Therefore, women who take raloxifene can expect a reduction in the likelihood of having a vertebral fracture, and possibly breast cancer. The lack of definitive efficacy against hip fracture is not a major deterrent to use of this agent in this age group because hip fracture risk is very low. Raloxifene might not be the treatment of choice for elderly women who are at particularly high risk of hip fracture.     

Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women

CONTEXT AND OBJECTIVE: Hip fracture is partially genetically determined. The present study was designed to examine the contributions of vitamin D receptor (VDR) and collagen I alpha1 (COLIA1) genotypes to the liability to hip fracture in postmenopausal women. DESIGN: The study was designed as a prospective population-based cohort investigation. SUBJECTS: Six hundred seventy-seven postmenopausal women of Caucasian background, aged 70 +/- 7 yr (mean +/- SD), have been followed for up to 14 yr. Sixty-nine women had sustained a hip fracture during the period. MAIN OUTCOME: Atraumatic hip fractures were prospectively identified through radiologists' reports. Bone mineral density (BMD) at the hip and lumbar spine was measured by dual-energy x-ray absorptiometry. GENOTYPES: The TaqI and SpI COLIA1 polymorphisms of the VDR and COLIA1 genes were determined. Using the Single Nucleotide Polymorphism database, VDR TT, Tt, and tt genotypes were coded as TT, TC, and CC, whereas COLIA1 SS, Ss, and ss were coded as GG, GT, and TT. RESULTS: Women with VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had an increased risk of hip fracture [odds ratio (OR) associated with CC, 2.6; 95% confidence interval (CI), 1.2-5.3; OR associated with TT, 3.8; 95% CI, 1.3-10.8] after adjustment for femoral neck BMD (OR, 3.4 per SD; 95% CI, 2.3-5.0) and age (OR, 1.4 per 5 yr; 95% CI, 1.1-1.7). Approximately 20 and 12% of the liability to hip fracture was attributable to the presence of the CC genotype and TT genotype, respectively. CONCLUSION: The VDR CC genotype and COLIA1 TT genotype were associated with increased hip fracture risk in Caucasian women, and this association was independent of BMD and age.     

Development and validation of the osteoporosis prescreening risk assessment (OPERA) tool to facilitate identification of women likely to have low bone density

Osteoporosis and its consequent increase in fracture risk is a major health concern for postmenopausal women and older men and has the potential to reach epidemic proportions. The "gold standard" for osteoporosis diagnosis is bone densitometry. However, economic issues or availability of the technology may prevent the possibility of mass screening. The goal of this study was to develop and validate a clinical scoring index designed as a prescreening tool to help clinicians identify which women are at increased risk of osteoporosis [bone mineral density (BMD) T-score -2.5 or less] and should therefore undergo further testing with bone densitometry. Records were analyzed for 1522 postmenopausal females over 50 years of age who had undergone testing with dual-energy X-ray absorptiometry (DXA). Osteoporosis risk index scores were compared to bone density T-scores. Hologic QDR 4500 technology was used to measure BMD at the femoral neck and lumbar spine (L1-L4). Participants who had a previous diagnosis of osteoporosis or were taking bone-active medication were excluded. Receiver-operating characteristic (ROC) analysis was used to identify the specific cutpoint value that would identify women at increased risk of low BMD. A simple algorithm based on age, weight, history of previous low impact fracture, early menopause, and corticosteroid therapy was developed. Validation of this five-item osteoporosis prescreening risk assessment (OPERA) index showed that the tool, at the recommended threshold (or cutoff value) of two, had a sensitivity that ranged from 88.1 [95% confidence interval (CI) for the mean: 86.2-91.9%] at the femoral neck to 90% (95% CI for the mean: 86.1-93.1%) at the lumbar spine area. Corresponding specificity values were 60.6 (95% CI for the mean: 57.9-63.3%) and 64.2% (95% CI for the mean: 61.4-66.9%), respectively. The positive predictive value (PPV) ranged from 29 at the femoral neck to 39.2% at the lumbar spine, while the corresponding negative predictive values (NPVs) reached 96.5 and 96.2%, respectively. Based on this cutoff value, the area under the ROC curve was 0.866 (95% CI for the mean: 0.847-0.882) for the lumbar spine and 0.814 (95% CI for the mean: 0.793-0.833) for the femoral neck. We conclude that the OPERA is a free and effective method for identifying Italian postmenopausal women at increased risk of osteoporosis. Its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.     

Measures of adiposity and risk of breast cancer in older postmenopausal women

OBJECTIVES: To determine whether higher adiposity is associated with greater breast cancer risk in older postmenopausal women. DESIGN: Prospective cohort study with mean follow-up of 11.3 years. SETTING: Four U.S. clinical centers. PARTICIPANTS: Seven thousand five hundred twenty-three women (mean age 73.5) enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Weight, height, and waist and hip circumference were measured at baseline. Body composition was determined using bioelectrical impedance. Risk factor information was obtained by interview and questionnaire. Bone mineral density was measured using dual energy x-ray absorptiometry. The outcome was incident invasive breast cancer, confirmed using medical records. RESULTS: After adjustment for multiple risk factors, including bone density, women in the uppermost quartiles of weight, weight gain since age 25, body mass index, waist circumference, and percentage of body fat had higher breast cancer rates than women in the first quartiles of each measure. For example, breast cancer rates were 49% higher for women in the uppermost quartile of weight (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.05-2.10), 64% higher for women in the top quartile of weight gain since age 25 (HR=1.64, 95% CI=1.15-2.34), and 58% higher for women in the top quartile of percentage of body fat (HR=1.58, 95% CI=1.11-2.23) than for women in the lowest quartile of each measure. The associations between adiposity measures and breast cancer rates were not altered when the analyses were limited to very elderly women (> or = 70). CONCLUSION: Higher adiposity is an independent risk factor for breast cancer in elderly women.     

Effect of raloxifene on bone mineral density in premenopausal women at increased risk of breast cancer

CONTEXT: Raloxifene is a promising breast cancer prevention agent in postmenopausal women at increased risk for breast cancer. The effects of raloxifene in premenopausal women are unknown. OBJECTIVE: We evaluated the effect of raloxifene in premenopausal women at increased risk for breast cancer on bone mineral density (BMD). DESIGN: This was a phase II clinical trial. SETTING: This study was conducted at an academic medical center. PARTICIPANTS: Thirty-seven premenopausal women at increased risk for breast cancer enrolled in the trial. Thirty subjects began treatment and 27 were evaluable. INTERVENTION: Raloxifene (60 mg daily) and elemental calcium (500 mg daily) were given for 2 yr. Subjects were followed up off medications for 1 yr. MAIN OUTCOME MEASURE: The primary end point was the intrasubject percent change in BMD at 1 yr measured by dual-energy x-ray absorptiometry. RESULTS: The mean baseline lumbar spine density was 1.027 g/cm(2). Lumbar spine density decreased 2.3% at 1 yr (P < 0.00001) and 3.5% at 2 yr (P < .00001). Percent change from yr 2 to 3 was +1.4%. The mean baseline total hip bone density was 0.905 g/cm(2). Total hip density decreased 0.3% at 1 yr and 1.0% at 2 yr (P = 0.033). Percent change from yr 2 to 3 was +1.7%. CONCLUSIONS: Raloxifene use is associated with a decrease in BMD in premenopausal women at increased risk for breast cancer. The clinical significance of this decrease is unknown and is attenuated with stopping raloxifene.     

Cigarette smoking, alcohol consumption, and risk of hip fracture in women

BACKGROUND: Previous studies regarding the impact of cigarette smoking on the risk of hip fracture in postmenopausal women have been inconsistent, suggesting different effects in different groups. The effect of alcohol intake on fracture risk is puzzling: moderate alcohol intake appears to increase bone density, and its association with hip fracture is not clear. METHODS: To assess the associations of cigarette smoking and alcohol consumption with hip fracture risk among postmenopausal women, we conducted an analysis of a population-based case-control study from Sweden. Cases were postmenopausal women, aged 50 to 81 years, who sustained a hip fracture after minor trauma between October 1, 1993, and February 28, 1995; controls were randomly selected from a population-based register during the same period. A mailed questionnaire requesting information on lifestyle habits and medical history was used 3 months after the hip fracture for cases and simultaneously for controls. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed by means of logistic regression. RESULTS: Of those eligible, 1328 cases (82.5%) and 3312 controls (81.6%) responded. Compared with never smokers, current smokers had an increased risk of hip fracture (age-adjusted OR, 1.66; 95% CI, 1.41-1.95). Duration of smoking-particularly postmenopausal smoking-was more important than the amount smoked. Former smokers had a small increase in risk (age-adjusted OR, 1.15; 95% CI, 0.97-1.37) that decreased with the duration of cessation. The age-adjusted OR for women consuming alcohol was 0.80 (95% CI, 0.69-0.93). CONCLUSIONS: Cigarette smoking is a risk factor for hip fracture among postmenopausal women; risk decreases after cessation. Alcohol consumption has a weak inverse association with risk.     

A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.     

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

OBJECTIVE: To determine if a missense change at codon 64 of ADRB3 (Trp64Arg), a candidate obesity gene, is associated with obesity and levels of subcutaneous or visceral fat in African-American breast cancer cases. Several observational studies have found that women, who are overweight or obese at the time of diagnosis, as well as those who gain weight after diagnosis, are at greater risk for breast cancer recurrence and death than non-overweight women. DESIGN: Prospective cohort of breast cancer cases. SUBJECTS: 219 African-American breast cancer patients participating in the Los Angeles component of the Health, Eating, Activity and Lifestyle Study. MEASURES: ADRB3 Trp64Arg genotype, measures of weight including body mass index (BMI), weight gain (weight 5 years before diagnosis compared with weight at 30 months after diagnosis), obesity (BMI> or =30 kg/m(2)), waist/hip circumference and visceral or subcutaneous fat were determined by magnetic resonance imaging. RESULTS: African-American women who were homozygous for the ADRB3 wild-type allele had significantly higher mean visceral fat levels than women who carried the variant (P=0.04), and were significantly more likely to be obese (odd ratios (OR)=2.1, 95% confidence interval (CI)=1.1-4.2). The association with obesity was most pronounced among women who were premenopausal (OR=4.8, 95% CI=1.3-18), who received chemotherapy for their breast cancer (OR=6.1, 95% CI=1.8-20), or who were not physically active (OR=3.9, 95% CI=1.5-9.7). CONCLUSION: The wild-type allele of the ADRB3 missense change was associated with measures of obesity in our sample of African-American women. The association was modified by menopausal status, history of chemotherapy and modest levels of physical activity. These results will need to be confirmed in an independent sample.     

Association between bone mineral density and cognitive decline in older women.

OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a marker of cumulative estrogen exposure, is associated with cognitive function in nondemented older women. DESIGN: A prospective cohort study. SETTING: Clinical centers in Baltimore, Maryland, Minneapolis, Minnesota, the Monongahela Valley near Pittsburgh, Pennsylvania, and Portland, Oregon. PARTICIPANTS: We evaluated 8333 older community-dwelling women enrolled in the Study of Osteoporotic Fractures who were not taking estrogen replacement. MEASUREMENTS: Calcaneal and hip BMD were measured at baseline and at follow-up (4-6 years later); vertebral fractures were ascertained radiologically at year 6. Women were administered a modified Mini-Mental State Exam, Trails B, and Digit Symbol at baseline and at follow-up. RESULTS: Compared with women with higher bone mineral density, women with low baseline BMD had up to 8% worse baseline cognitive scores (P = .001) and up to 6% worse repeat cognitive scores (P = .001), even after multivariate adjustments. For 1 SD decrease in baseline hip BMD or calcaneal BMD, women had a 32% (95% CI, 19-47%) or a 33% (95% CI, 20-48%) greater odds of cognitive deterioration (worst 10th percentile of change). Women with vertebral fractures had lower cognitive test scores and a greater odds of cognitive deterioration than those without fractures (OR = 1.29; 95% CI, 1.03-1.60). CONCLUSIONS: Women with osteoporosis, whether measured by baseline BMD, reductions in BMD, or vertebral fractures, have poorer cognitive function and greater risk of cognitive deterioration. Our findings suggest a link between two of the most common conditions affecting older women. Further understanding of this association may be important for new treatment and prevention directions.