Judith Shary

The effects of muscle-building exercise on bone mineral density of the radius, spine, and hip in young men

SummaryWe previously demonstrated that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)2D, and urinary cyclic AMP. These studies were interpreted to mean that this form of exercise increases bone formation and modifies the vitamin D-endocrine system to provide more calcium for bone. The present investigation was carried out in normal young adult white men to determine the effects of exercise on bone mineral density at weight-bearing and nonweight-bearing sites. Twelve men who had regularly engaged in muscle-building exercises (use of weights, exercise machines, or both) for at least 1 year and 50 age-matched controls (aged 19–40 years) were studied. The body weights of the two groups were not different from each other (78±2 vs. 74±1 kg, NS). Bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry, and BMD of the midradius was measured by single-photon absorptiometry. It was found that muscle-building exercise was associated with increased BMD at the lumbar spine (1.35±0.03 vs. 1.22±0.02 g/cm2,P<0.01), trochanter (0.99±0.04 vs. 0.86±0.02 g/cm2,P<0.01), and femoral neck (1.18 ±0.03 vs. 1.02±0.02 g/cm2,P<0.001) but not at the midradius (0.77±0.02 vs. 0.77±0.01 g/cm2, NS). These studies provide additional evidence that muscle-building exercise is associated with increases in BMD at weight-bearing sites but not at nonweight-bearing sites.

Demonstration that bone mineral density of the lumbar spine, trochanter, and femoral neck is higher in black than in white young men

The incidence of osteoporosis and fractures of the hip and spine is lower in black than in white subjects. To determine whether bone mass is increased in black men and to assess the influence of body weight and age, bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry in 59 normal white men and 40 black men between the ages of 20 and 50 years. Body weight and age were not different from each other in the two groups. BMD of the midradius was measured by single-photon absorptiometry. Multivariate regression was used for independent analysis of each group and for analysis of the two groups together. After adjusting for body weight, age was inversely related to BMD of the femoral neck in both blacks and whites and of the trochanter in blacks. When body weight was analyzed independently of age, it was a positive predictor for BMD of the midradius of black men and of the femoral neck in white men. Despite the racial differences in age and weight on BMD, there were no significant interactions between race and age or race and weight when the data from black and white men were combined. Race had a highly significant effect on BMD of the lumbar spine, trochanter, and femoral neck midradius, and BMD was higher in blacks than in whites at these sites. There were significant declines in BMD with age at the midradius and femoral neck and significant increases in BMD with body weight at the trochanter and femoral neck. Thus, bone mass is higher in black than in white men and the difference in bone mass may contribute to the lower incidence of osteoporosis and fractures in blacks.

Diclofenac sodium inhibits bone resorption in postmenopausal women

BACKGROUND The results of experimental studies with animals indicated that prostaglandins stimulate bone resorption, that skeletal production of prostaglandin E2 is enhanced by ovariectomy and is diminished by 17 beta-estradiol, and that the nonsteroidal anti-inflammatory drug (NSAID) naproxyn prevents bone loss after ovariectomy. Studies were carried out to investigate the effects of the NSAID diclofenac sodium on bone and mineral metabolism in premenopausal women and to compare the effects of diclofenac sodium and conjugated estrogens on bone and mineral metabolism in postmenopausal women. PATIENTS AND METHODS Ten healthy premenopausal women and 17 healthy postmenopausal women were studied while not being treated and again after 4 weeks of treatment with diclofenac sodium, 150 mg per day in divided doses (both groups), and conjugated estrogens, 0.625 mg per day (postmenopausal women). Cross-linked N-telopeptides of type I collagen were measured in the urine as an index of bone resorption. The postmenopausal women were separated into two groups, responders and nonresponders, based on their response to conjugated estrogens as assessed by linear discriminant analysis for groups. Conjugated estrogens lowered urinary N-telopeptides of type I collagen in responders, but not in nonresponders. RESULTS Urinary cross-linked N-telopeptides were higher in the eight postmenopausal women responders than in the nine postmenopausal nonresponders or in the premenopausal women, and were not altered by diclofenac sodium in premenopausal women. In the eight postmenopausal women with higher rates of bone resorption, diclofenac sodium and conjugated estrogens significantly lowered both urinary calcium concentration and urinary cross-linked N-telopeptides. The effects of the two drugs were comparable. CONCLUSION The preliminary results demonstrate that, at the dose used, diclofenac sodium is almost as effective as conjugated estrogens for decreasing bone loss in postmenopausal women. Further studies will be needed to determine whether diclofenac sodium can prevent postmenopausal bone loss.

Circulating Cathelicidin Concentrations in a Cohort of Healthy Children: Influence of Age, Body Composition, Gender and Vitamin D Status

Cathelicidin is an antimicrobial peptide whose circulating levels are related to vitamin D status in adults. This study sought to determine if circulating cathelicidin concentrations in healthy children are related to the age of the child, body composition and vitamin D status at birth and at the time of the study visit. Blood samples were obtained during yearly visits from 133 children, ages 2–7, whose mothers had participated in a pregnancy vitamin D supplementation RCT. Radioimmunoassay and ELISA were performed to analyze 25(OH)D and cathelicidin, respectively. Statistical analyses compared cathelicidin concentrations with concentrations of 25(OH)D at various time points (maternal levels throughout pregnancy, at birth, and child’s current level); and with race/ethnicity, age, gender, BMI, percent fat, and frequency of infections using Student’s t-test, χ2, Wilcoxon ranked-sum analysis, and multivariate regression. The cohort’s median cathelicidin concentration was 28.1 ng/mL (range: 5.6–3368.6) and did not correlate with 25(OH)D, but was positively correlated with advancing age (ρ = 0.236 & p = 0.005, respectively). Forty patients evaluated at two visits showed an increase of 24.0 ng/mL in cathelicidin from the first visit to the next (p<0.0001). Increased age and male gender were correlated with increased cathelicidin when controlling for race/ethnicity, percent fat, and child’s current 25(OH)D concentration (p = 0.028 & p = 0.047, respectively). This study demonstrated that as children age, the concentration of cathelicidin increases. Furthermore, male gender was significantly associated with increased cathelicidin concentrations. The lack of association between vitamin D status and cathelicidin in this study may be due to the narrow range in observed 25(OH)D values and warrants additional studies for further observation.

Analysis of the NICHD Vitamin D Pregnancy Cohort on a Per-Protocol vs. Intent-to-Treat Basis: The Effect of Adherence on Trial Results

Objective: To perform per-protocol analysis of data obtained from the NICHD vitamin D pregnancy study published by Hollis et al., which found via intent-to-treat analysis that 4000IU/day vitamin D supplementation is safe and effective in achieving sufficiency in women and neonates. This study hypothesizes that differential adherence as examined by per-protocol analysis will affect the magnitude of differences in maternal and neonatal vitamin D status between treatment groups.Study design: A double-blind, RCT of vitamin D supplementation (400, 2000 or 4000IU/day) in 350 Caucasian, African American and Hispanic women with singleton pregnancies was conducted. This study defines adherence as 75% and 85% of pills taken between visits and examines the effect of adherence on vitamin D status across treatment groups. The primary outcome, measured by radioimmunoassay, is maternal serum 25(OH)D throughout pregnancy, one month prior to delivery (PTD) and neonatal serum 25(OH)D at delivery.Results: No statistically significant difference in maternal 25(OH)D throughout pregnancy, 1-month PTD, or neonatal 25(OH)D were found between 75% adherent participants and nonadherent participants regardless of supplementation. At 85% adherence, maternal 25(OH)D throughout pregnancy, one month PTD, and neonatal 25(OH)D were significantly higher in the 4000IU group compared to nonadherent participants (p=0.0002, p=0.0074, p=0.0068, respectively). No significant differences were found with 400 or 2000IU supplementation regardless of adherence.Conclusions: Participants 85% adherent to protocol and receiving 4000IU vitamin D were the only group that demonstrated significantly higher vitamin D status for each outcome: maternal 25(OH)D throughout pregnancy, 1-month PTD and neonatal 25(OH)D. Compared to intent-to-treat, this powerful per-protocol analysis demonstrates the impact that nonadherence can have on study results and has implications for how clinical trial data are analyzed and presented.

Bone mineral density during pregnancy in women participating in a randomized controlled trial of vitamin D supplementation

Background: Little is known about bone mineral density (BMD) during pregnancy. Advances in technology with lower radiation emissions by dual-energy X-ray absorptiometry instruments now permit the safe measurement of BMD during pregnancy.Objective: We evaluated maternal BMD during pregnancy as a function of vitamin D status in women of diverse racial/ethnic backgrounds.Design: A total of 301 women who underwent BMD measurements at 12-20 wk of gestation and again at 0-14 wk postpartum were included in this analysis. Women were a subset of subjects who were recruited for a randomized, controlled, double-blind trial of vitamin D supplementation in pregnancy (400, 2000, or 4000 IU/d).Results: Treatment had no significant effect on changes in BMD that occurred between 12-20 wk of gestation and 0-14 wk postpartum. Similarly, changes in spine and femoral neck bone mineral contents (BMCs) were not significantly different in the treatment groups. In addition, vitamin D inadequacy (serum 25-hydroxyvitamin D concentration, averaged across pregnancy, <50 nmol/L) was not associated with changes in BMD or BMC. There were significant racial/ethnic differences in spine BMD. African Americans lost more spine BMD than did Caucasians (-0.04 ± 0.04 compared with -0.02 ± 0.04 g/cm2; P = 0.033). In addition, baseline obesity was associated with a greater loss of femoral neck BMD. The means ± SDs of femoral neck BMD loss were -0.02 ± 0.05 and 0.0 ± 0.03 g/cm2 for groups with baseline body mass index (BMI; in kg/m2) ≥30 and <30, respectively.Conclusion: These findings do not support a dose effect of vitamin D supplementation on bone health and suggest that race/ethnicity and BMI play an important role in pregnancy bone health. This trial was registered at clinicaltrials.gov as NCT00292591.