Catherine Womack

Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes.

CONTEXT Type 2 diabetes mellitus (DM) is associated with higher bone mineral density (BMD) and paradoxically with increased fracture risk. It is not known if low BMD, central to fracture prediction in older adults, identifies fracture risk in patients with DM. OBJECTIVE To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 DM. DESIGN, SETTING, AND PARTICIPANTS Data from 3 prospective observational studies with adjudicated fracture outcomes (Study of Osteoporotic Fractures [December 1998-July 2008]; Osteoporotic Fractures in Men Study [March 2000-March 2009]; and Health, Aging, and Body Composition study [April 1997-June 2007]) were analyzed in older community-dwelling adults (9449 women and 7436 men) in the United States. MAIN OUTCOME MEASURE Self-reported incident fractures, which were verified by radiology reports. RESULTS Of 770 women with DM, 84 experienced a hip fracture and 262 a nonspine fracture during a mean (SD) follow-up of 12.6 (5.3) years. Of 1199 men with DM, 32 experienced a hip fracture and 133 a nonspine fracture during a mean (SD) follow-up of 7.5 (2.0) years. Age-adjusted hazard ratios (HRs) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 (95% confidence interval [CI], 1.43-2.48) for hip fracture and 1.52 (95% CI, 1.31-1.75) for nonspine fracture, and in men with DM were 5.71 (95% CI, 3.42-9.53) for hip fracture and 2.17 (95% CI, 1.75-2.69) for nonspine fracture. The FRAX score was also associated with fracture risk in participants with DM (HRs for 1-unit increase in FRAX hip fracture score, 1.05; 95% CI, 1.03-1.07, for women with DM and 1.16; 95% CI, 1.07-1.27, for men with DM; HRs for 1-unit increase in FRAX osteoporotic fracture score, 1.04; 95% CI, 1.02-1.05, for women with DM and 1.09; 95% CI, 1.04-1.14, for men with DM). However, for a given T score and age or for a given FRAX score, participants with DM had a higher fracture risk than those without DM. For a similar fracture risk, participants with DM had a higher T score than participants without DM. For hip fracture, the estimated mean difference in T score for women was 0.59 (95% CI, 0.31-0.87) and for men was 0.38 (95% CI, 0.09-0.66). CONCLUSIONS Among older adults with type 2 DM, femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk; however, in these patients compared with participants without DM, the fracture risk was higher for a given T score and age or for a given FRAX score.

Fracture Risk in Men With Congestive Heart Failure: Risk Reduction With Spironolactone

OBJECTIVES The purpose of this study was to determine whether spironolactone use is associated with fractures in men with congestive heart failure (CHF). BACKGROUND In rats with aldosteronism, spironolactone preserves skeletal strength. However, in humans, the relationship of spironolactone to fractures is not known. METHODS The medical records of all male patients with CHF from 1999 to 2005 treated at the Veterans Affairs Medical Center, Memphis, Tennessee, were reviewed (n = 4,735). Odds ratios with 95% confidence intervals of having a fracture associated with spironolactone use were estimated using conditional logistic regression. RESULTS We identified 167 cases with a single-incident fracture and matched these by age and race to 668 control subjects without fractures. After adjustment for covariates, spironolactone use was inversely associated with total fracture (odds ratio: 0.575; 95% confidence interval: 0.346 to 0.955, p = 0.0324). CONCLUSIONS The use of spironolactone is inversely associated with fractures in men with CHF.

Association of Spinal Muscle Composition and Prevalence of Hyperkyphosis in Healthy Community-Dwelling Older Men and Women

BACKGROUND Older adults with hyperkyphosis are at increased risk of falls, fractures, and functional decline. Modifiable risk factors for hyperkyphosis have not been well studied. Our objective was to determine whether spinal muscle area and density are associated with hyperkyphosis, independent of age, race, sex, bone mineral density, and trunk fat. METHODS Using data from the Pittsburgh site of the Health, Aging, and Body Composition study, we performed a baseline cross-sectional analysis. Participants were black and white men and women 70-79 years old (N = 1172), independent in activities of daily living and able to walk ¼ mile and up 10 steps without resting. We measured Cobbs angle of kyphosis from supine lateral scout computed tomography scans, and categorized hyperkyphosis as Cobbs angle >40°. Axial images from lateral scout computed tomography scans assessed spinal extensor muscle cross-sectional area and density (proxy for fat infiltration). RESULTS In our sample, 21% had hyperkyphosis. Prevalence in black men was 11%; in white men, 17%; in black women, 26%; and in white women, 30%. In multivariate analysis, each standard deviation increase in muscle density was associated with a 29% reduction in the odds of hyperkyphosis, independent of covariates. Muscle area was not significantly associated with hyperkyphosis. CONCLUSIONS Lower spinal muscle density is associated with hyperkyphosis in healthy community-dwelling older adults. This potentially modifiable risk factor could be targeted in exercise interventions. Randomized trials are needed to determine whether an exercise program targeting spinal muscle density reduces hyperkyphosis and in turn improves health outcomes.

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

ObjectiveThe objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. MethodsThe parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women’s Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. ResultsThere was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46–mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). ConclusionsSupplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.

Preliminary Findings: 25(OH)D Levels and PTH Are Indicators of Rapid Bone Accrual in Pubertal Children

Objective: The objective of this study was to evaluate the role of serum levels of 25(OH)D and PTH on the accumulation of whole body bone mass in a cohort of children. Methods: This was a longitudinal study (1.98 ± 0.07 y) of sixty-nine children (89% Caucasian, 44% male) enrolled in a calcium supplementation trial. Bone area, bone mineral content (BMC) and density (BMD) of the whole body and radius were assessed using a QDR 2000 (Hologic, Inc) dual energy x-ray absorptiometer. Serum PTH and 25(OH)D were measured using radioimmunoassays. Results: Vitamin D stores were inversely related gain in bone area (p < 0.002), BMC (p < 0.002) BMD (p < 0.027), as well as to PTH levels (p < 0.0001). Compared to those with adequate vitamin D stores (>34 ng/ml), those who had consistently low vitamin D stores (18 ng/ml) had a 8% larger gain in bone area (p < 0.05); 11% in BMC (p < 0.05) and no differences in gain in BMD; after adjusting for baseline bone measurements, race, gender, season measured, Tanner stage, and calcium intake. Conclusions: High normal PTH with low-normal 25(OH)D stores and moderate to high calcium intake may be beneficial to accruing larger bone size and BMC during puberty.

Appendicular fractures: A significant problem among institutionalized adults with developmental disabilities

A high incidence of nontraumatic fracture in adults with developmental disabilities living in a state-run facility was described. Risk factors for fracture, including bone mineral density (BMD), were investigated to determine whether people at highest risk for fracture could be prospectively identified. There was a 7.3% incidence of fracture among 391 adults. Risk factors were examined for 23 residents with fracture and 23 age-, race-, and gender-matched controls. There was a trend for antiepileptic medication usage to be associated with fractures. Estimated BMD by heel ultrasound did not predict fracture; however, values were much lower than those for the general population. Fractures and low BMD are significant problems among institutionalized adults with severe developmental disabilities. Further studies to identify therapies to prevent fractures are warranted.

Use of and interest in mobile health for diabetes self-care in vulnerable populations.

Objective We aimed to assess use of and interest in mobile health (mHealth) technology and in-person services for diabetes self-care in vulnerable populations. Methods We delivered a self-administered cross-sectional survey. Participants were recruited at two primary care practices (P1 and P2) with P1 located in a medically underserved area and P2 in an affluent suburb. Two-sample t-tests and chi-square tests were used with p < 0.05 significant. In addition, a secondary analysis was performed to analyse differences in use and interest in mHealth by age. Results Of 75 eligible patients, 60 completed the survey (80% response rate). P1 patients had significantly higher interest in three of five categories of in-person diabetes support services, one of four categories of health-related text messages (TM), and three of eight categories of mHealth applications (p < 0.05). Smartphone users reported higher interest in TM (p = 0.004) and mHealth applications for diabetes self-care (p = 0.004). Younger patients were more likely to have a smartphone (p < 0.006), use the Internet (p < 0.0012), use smartphone applications (p < 0.0004), and to be interested in using applications to manage their diabetes (p < 0.004). Discussion This study shows substantial patient interest in TM and mHealth applications for diabetes self-care and suggests that patients in underserved areas may have particularly high interest in using mHealth solutions in primary care. Younger patients and smartphone users were more likely to be interested in using applications to manage their diabetes. As more patients use smartphones, interest in using mHealth to support patient self-care and strengthen primary care infrastructure will continue to grow.

Low-Fat Dietary Pattern and Breast Cancer Mortality in the Women’s Health Initiative Randomized Controlled Trial

Purpose Earlier Womens Health Initiative Dietary Modification trial findings suggested that a low-fat eating pattern may reduce breast cancers with greater mortality. Therefore, as a primary outcome-related analysis from a randomized prevention trial, we examined the long-term influence of this intervention on deaths as a result of and after breast cancer during 8.5 years (median) of dietary intervention and cumulatively for all breast cancers diagnosed during 16.1 years (median) of follow-up. Patients and Methods The trial randomly assigned 48,835 postmenopausal women with normal mammograms and without prior breast cancer from 1993 to 1998 at 40 US clinical centers to a dietary intervention with goals of a reduction of fat intake to 20% of energy and an increased intake of fruits, vegetables, and grains (40%; n = 19,541) or to a usual diet comparison (60%; n = 29,294). Results In the dietary group, fat intake and body weight decreased (all P < .001). During the 8.5-year dietary intervention, with 1,764 incident breast cancers, fewer deaths occurred as a result of breast cancer in the dietary group, which was not statistically significant (27 deaths [0.016% per year] v 61 deaths [0.024% per year]; hazard ratio [HR], 0.67; 95% CI, 0.43 to 1.06; P = .08). During the same period, deaths after breast cancer (n = 134) were significantly reduced (40 deaths [0.025% per year] v 94 deaths [0.038% per year]; HR, 0.65; 95% CI, 0.45 to 0.94; P = .02) by the dietary intervention. During the 16.1-year follow-up, with 3,030 incident breast cancers, deaths after breast cancer also were significantly reduced (234 deaths [0.085% per year] v 443 deaths [0.11% per year]; HR, 0.82; 95% CI, 0.70 to 0.96; P = .01) in the dietary group. Conclusion Compared with a usual diet comparison group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer.

Calcium Plus Vitamin D Supplementation and Joint Symptoms in Postmenopausal Women in the Women's Health Initiative Randomized Trial

BACKGROUND Low vitamin D intake and levels have been associated with increased joint symptoms in some observational studies but the findings are mixed and evidence from randomized trials sparse. OBJECTIVE To evaluate the influence of supplemental calcium and vitamin D on joint symptoms in the Womens Health Initiative randomized, placebo-controlled, clinical trial. DESIGN In post hoc analyses, the results of the Womens Health Initiative randomized clinical trial in which 36,282 postmenopausal women were randomized to receive calcium carbonate (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were examined in the 6% subgroup of 1,911 participants, oversampled for minorities, who had serial joint symptom assessment. Qualitative information on joint pain and joint swelling was collected by questionnaire before entry and 2 years after randomization. Logistic regression models were used to compare the occurrence and severity of joint symptoms across randomization groups. RESULTS At baseline, total calcium and vitamin D intakes from diet and supplements were similar in the two randomization groups. In addition, both joint pain (reported by 73%) and joint swelling (reported by 34%) were commonly reported and comparable in the supplement and placebo groups. Two years after randomization, no statistically significant differences between supplement and placebo groups were seen for joint pain frequency (74.6% compared with 75.1% [P=0.79] for supplement and placebo groups, respectively) or joint swelling frequency (34.6% compared with 32.4% [P=0.29], respectively) or in severity scores for either outcome. Subgroup analyses suggested study participants also using nonprotocol calcium supplements at study entry may have less joint pain with supplement group randomization (interaction P=0.02). CONCLUSIONS Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg calcium carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms.

Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative.

Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Womens Health Initiative Observational Study (WHI‐OS) and Clinical Trial (WHI‐CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50–79 years between 1993 and 1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)‐min/week: none <100 (reference), low 100 to <500, medium 500 to <1,200, high 1,200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow‐up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared with no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p = 0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76–0.96); medium, HR: 0.82 (0.73–0.93); and high, HR: 0.90 (0.79–1.03)], and mortality [p < 0.0001; low, HR: 0.80 (0.69–0.92); medium, HR: 0.68 (0.59–0.80); and high, HR: 0.78 (0.66–0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p = 0.01), with a stronger association in women with BMI < 30 kg/m2. Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non‐obese women.