Additive benefit of higher testosterone levels and vitamin D plus calcium supplementation in regard to fall risk reduction among older men and women

Summary: Higher physiologic testosterone levels among community dwelling older men and women may protect against falls, and this benefit may be further increased among those taking additional vitamin D plus calcium. Introduction: The aim of this study is to investigate sex hormone levels and fall risk in older men and women. Methods: One hundred and ninety-nine men and 246 women age 65+ living at home were followed for 3years after baseline assessment of sex hormones. Analyses controlled for several covariates, including baseline 25-hydroxyvitamin D, sex hormone binding globulin, and vitamin D plus calcium treatment (vitD+cal). Results: Compared to the lowest quartile, men and women in the highest quartile of total testosterone had a decreased odds of falling (men: OR = 0.22; 95% CI [0.07,0.72]/ women: OR = 0.34; 95% CI [0.14,0.83]); if those individuals also took vitD+cal, the fall reduction was enhanced (men: OR = 0.16; 95% CI [0.03,0.90] / women: OR = 0.15; 95% CI [0.04,0.57]). Similarly, women in the top quartile of dihydroepiandrosterone sulfate (DHEA-S) had a lower risk of falling (OR = 0.39; 95% CI [0.16,0.93]). Other sex hormones and SHBG did not predict falling in men or women. Conclusions: Higher testosterone levels in both genders and higher DHEA-S levels in women predicted a more than 60% lower risk of falling. With vitD+cal, the anti-fall benefit of higher physiologic testosterone levels is enhanced from 78% to 84% among men and from 66% to 85% among wome

Benefit-risk assessment of vitamin D supplementation

Summary: Current intake recommendations of 200 to 600IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. Introduction: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. Methods and results: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000IU vitamin D per day or mean 25(OH)D between 75 and 110nmol/l (30-44ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000IU per day or achieved 25(OH)D up to 643nmol/l. Mean levels of 75 to 110nmol/l were reached in most RCTs with 1,800 to 4,000IU vitamin D per day without risk. Conclusion: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the populatio

Effect of body composition methodology on heritability estimation of body fatness

Heritability estimates of human body fatness vary widely and the contribution of body composition methodology to this variability is unknown. The effect of body composition methodology on estimations of genetic and environmental contributions to body fatness variation was examined in 78 adult male and female monozygotic twin pairs reared apart or together. Body composition was assessed by six methods - body mass index (BMI), dual energy x-ray absorptiometry (DXA), underwater weighing (UWW), total body water (TBW), bioelectric impedance (BIA), and skinfold thickness. Body fatness was expressed as percent body fat, fat mass, and fat mass/height2 to assess the effect of body fatness expression on heritability estimates. Model-fitting multivariate analyses were used to assess the genetic and environmental components of variance. Mean BMI was 24.5 kg/m2 (range of 17.8-43.4 kg/m2). There was a significant effect of body composition methodology (p<0.001) on heritability estimates, with UWW giving the highest estimate (69%) and BIA giving the lowest estimate (47%) for fat mass/height2. Expression of body fatness as percent body fat resulted in significantly higher heritability estimates (on average 10.3% higher) compared to expression as fat mass/height2 (p=0.015). DXA and TBW methods expressing body fatness as fat mass/height2 gave the least biased heritability assessments, based on the small contribution of specific genetic factors to their genetic variance. A model combining DXA and TBW methods resulted in a relatively low FM/ht2 heritability estimate of 60%, and significant contributions of common and unique environmental factors (22% and 18%, respectively). The body fatness heritability estimate of 60% indicates a smaller contribution of genetic variance to total variance than many previous studies using less powerful research designs have indicated. The results also highlight the importance of environmental factors and possibly genotype by environmental interactions in the etiology of weight gain and the obesity epidemic.R01 AR046124 - NIAMS NIH HHS; R01 MH065322 - NIMH NIH HHS; T32 HL069772 - NHLBI NIH HHS; R21 DK078867 - NIDDK NIH HHS; R37 DA018673 - NIDA NIH HHS; R01 DK076092 - NIDDK NIH HHS; R01 DK079003 - NIDDK NIH HHS; F32 DK009747 - NIDDK NIH HHS; R01 DA018673 - NIDA NIH HH

Interstate Variation in the Burden of Fragility Fractures

Demographic differences may produce interstate variation in the burden of osteoporosis. We estimated the burden of fragility fractures by race/ethnicity, age, sex, and service site across five diverse and populous states. State inpatient databases for 2000 were used to describe hospital fracture admissions, and a Markov decision model was used to estimate annual fracture incidence and cost for populations ≥50 yr of age for 2005–2025 in Arizona (AZ), California (CA), Florida (FL), Massachusetts (MA), and New York (NY). In 2000, mean hospital charges for incident fractures varied 1.7-fold across states. For hip fracture, mean charges ranged from $16,700 (MA) to$29,500 (CA), length of stay from 5.3 (AZ) to 8.9 days (NY), and discharge rate to long-term care from 43% (NY) to 71% (CA). In 2005, projected fracture incidence rates ranged from 199 (CA) to 266 (MA) per 10,000. Total cost ranged from $270 million (AZ) to$1,434 million (CA). Men accounted for 26–30% of costs. Across states, hip fractures constituted on average 77% of costs; “other” fractures (e.g., leg, arm), 10%; pelvic, 6%; vertebral, 5%; and wrist, 2%. By 2025, Hispanics are projected to represent 20% of fractures in AZ and CA and Asian/Other populations to represent 27% of fractures in NY. In conclusion, state initiatives to prevent fractures should include nonwhite populations and men, as well as white women, and should address fractures at all skeletal sites. Interstate variation in service utilization merits further evaluation to determine efficient and effective disease management strategies

Plasma 25-Hydroxyvitamin D Concentration and Risk of Incident Type 2 Diabetes in Women

OBJECTIVE — To determine the association between 25-hydroxyvitamin D (25-OHD) con-centration and risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS — In a nested case-control study conducted among 608 women with newly diagnosed type 2 diabetes and 559 control subjects in the Nurses’ Health Study, we measured the association between baseline plasma 25-OHD concentration and risk of incident diabetes. RESULTS — After adjusting for matching factors and diabetes risk factors, including BMI, higher levels of plasma 25-OHD were associated with a lower risk for type 2 diabetes. The odds ratio for incident type 2 diabetes in the top (median 25-OHD, 33.4 ng/ml) versus the bottom (median 25-OHD, 14.4 ng/ml) quartile was 0.52 (95 % CI 0.33–0.83). The associations were consistent across subgroups of baseline BMI, age, and calcium intake. CONCLUSIONS — Plasma 25-OHD concentration was associated with lower risk of inci-dent type 2 diabetes in women. Diabetes Care 33:2021–2023, 2010 G rowing evidence indicates that sub-optimal vitamin D status may play arole in the development of type 2 diabetes (1). Results from longitudinal observational studies support the hypoth-esis that low vitamin D status is associated with development of type 2 diabetes; however, only one study has examined the association between blood 25-hydroxyvitamin D (25-OHD) concentra-tion and incident type 2 diabetes, and there was no significant association among women (2,3). We examined pro-spectively the association between plasma 25-OHD concentration and risk of inci-dent type 2 diabetes among women in a case-control study nested within th

Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes

OBJECTIVE To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. RESEARCH DESIGN AND METHODS Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying “lagged” covariates, as the mean of the previous and current visits at which diabetes status was assessed. RESULTS After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56–0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52–0.94) versus lifestyle arm (0.80; 0.54–1.17). CONCLUSIONS Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies

Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents

Summary: The effect of equivalent oral doses of vitamin D3 600 IU/day, 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a randomized clinical trial in nursing home residents. A daily dose was more effective than a weekly dose, and a monthly dose was the least effective. Introduction: It is assumed that equivalent daily, weekly or monthly doses of vitamin D3 equally influence vitamin D status. This was investigated in a randomized clinical trial in nursing home residents. Methods: The study was performed in ten nursing homes including 338 subjects (76 male and 262 female), with a mean age of 84 (± SD 6.3 years). They received oral vitamin D3 either 600 IU/day, or 4200 IU/week, or 18,000 IU/month or placebo. After 4 months, calcium was added during 2 weeks, 320 mg/day or 640 mg/day or placebo. Outcome: serum levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone turnover markers. Statistical approach: linear multilevel analysis. Results: At baseline, mean serum 25(OH)D was 25.0 nmol/L (SD 10.9), and in 98%, it was lower than 50 nmol/L. After 4 months, mean serum 25(OH)D levels increased to 62.5 nmol/L (after daily vitamin D3 69.9 nmol/L, weekly 67.2 nmol/L and monthly 53.1 nmol/L, P<0.001 between groups). Median serum PTH levels decreased by 23% (p<0.001). Bone turnover markers did not decrease. Calcium supplementation had no effect on serum PTH and bone turnover. Conclusion: Daily vitamin D was more effective than weekly, and monthly administration was the least effective. © 2007 International Osteoporosis Foundation and National Osteoporosis Foundation

Updated fracture incidence rates for the US version of FRAX®

# The Author(s) 2009. This article is published with open access at Springerlink.com Summary On the basis of updated fracture and mortality data, we recommend that the base population values used in the US version of FRAX ® be revised. The impact of suggested changes is likely to be a lowering of 10-year fracture probabilities. Introduction Evaluation of results produced by the US version of FRAX ® indicates that this tool overestimates the likelihood of major osteoporotic fracture. In an attempt to correct this, we updated underlying fracture and mortality rates for the model. Methods We used US hospital discharge data from 2006 t

Calcifediol versus vitamin D3 effects on gait speed and trunk sway in young postmenopausal women: a double-blind randomized controlled trial

UNLABELLED In this double-blind RCT, 4-month treatment with calcifediol compared with vitamin D3 improved gait speed by 18 % among young postmenopausal women. Consistently, change in 25(OH)D blood levels over time were significantly correlated with improvement in gait speed in these women. No effect could be demonstrated for trunk sway. INTRODUCTION The aim of this study is to test the effect of calcifediol compared with vitamin D3 on gait speed and trunk sway. METHODS Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ng/ml (SD = ±3.9) and a mean age of 61.5 years (SD = ±7.2) were randomized to either 20 μg of calcifediol or 20 μg (800 IU) of vitamin D3 per day in a double-blind manner. At baseline and at 4 months of follow-up, the same physiotherapist blinded to treatment allocation tested 8-m gait speed and a body sway test battery (Sway star pitch and roll angle plus velocity while walking 8 m, and standing on both legs on a hard and soft surface). All analyses adjusted for baseline measurement, age, and body mass index. RESULTS Mean 25(OH)D levels increased to 69.3 ng/ml (SD = ±9.5) in the calcifediol group and to 30.5 ng/ml (SD = ±5.0) in the vitamin D3 group (p < 0.0001). Women receiving calcifediol compared with vitamin D3 had an 18 % greater improvement in gait speed at 4-month follow-up (p = 0.046) adjusting for baseline gait speed, age, and body mass index. Also, change in gait speed was significantly correlated with change in serum 25(OH)D concentrations (r = 0.5; p = 0.04). Across three tests of trunk sway, there were no consistent differences between groups and no significant correlation between change in 25(OH)D serum concentrations and change in trunk sway. CONCLUSIONS Calcifediol improved gait speed in early postmenopausal women compared with vitamin D3 and change in 25(OH)D level was moderately correlated with improvement in gait speed. A benefit on trunk sway could not be demonstrated

Assessment of the performance of the SarQoL questionnaire in screening for sarcopenia in older people

Background: Because of its low prevalence and the need for physical tests to establish a diagnosis, recruiting sarcopenic people for clinical studies can be a resource-intensive process. Aims: We investigated whether the SarQoL®, a 55-item questionnaire designed to measure quality of life in sarcopenia, could be used to identify older people with a high likelihood of being sarcopenic, and to compare its performance to the SARC-F tool. Methods: We performed a secondary analysis of data from older, community-dwelling participants of the SarcoPhAge study, evaluated for sarcopenia according to the EWGSOP2 criteria, and who completed the SarQoL® and SARC-F questionnaires. We determined the optimal threshold to distinguish between sarcopenic and non-sarcopenic people with the Youden index. Screening performance was evaluated with the area under the curve (AUC) and by calculating sensitivity and specificity. Results: The analysis of 309 participants provided an optimal threshold value of ≤ 52.4 points for identifying people with sarcopenia with the SarQoL® questionnaire, which resulted in a sensitivity of 64.7% (41.1–84.2%), a specificity of 80.5% (75.7–84.7%) and an AUC of 0.771 (0.652–0.889). Compared to the SARC-F, the SarQoL® has greater sensitivity (64.7% vs 52.39%), but slightly lower specificity (80.5% vs. 86.6%). Discussion: The SarQoL® questionnaire showed acceptable screening accuracy, on par with the SARC-F. The optimal threshold of ≤ 52.4 points should be confirmed in other cohorts of older people. Conclusions: This exploratory study showed that the SarQoL® could potentially be applied in a screening strategy, with the added benefit of providing a measure of QoL at the same time