Post-hoc comparison of vitamin D status at three timepoints during pregnancy demonstrates lower risk of preterm birth with higher vitamin D closer to delivery.

There have been observational reports that maternal vitamin D status at baseline and not closest to delivery is a better predictor of pregnancy outcomes, suggesting that a cascade of events is set into motion that is not modifiable by vitamin D supplementation during later pregnancy. To address this issue, in this exploratory post-hoc analysis using correlation and logistic regression, we sought to measure the strength of the association between serum 25(OH)D concentrations at 3 timepoints during pregnancy: baseline, 1st trimester (<16 weeks); 2nd trimester (16-26 weeks); and 3rd trimester (≥27 weeks) and preterm birth. It was hypothesized that the 25(OH)D value closest to delivery would be most significantly associated with preterm birth. To accomplish this objective, the datasets from NICHD (n=333) and Thrasher Research Fund (n=154) vitamin D supplementation pregnancy studies were combined. The results of this analysis were that 25(OH)D values closer to delivery were more strongly correlated with gestational age at delivery than earlier values: 1st trimester: r=0.11 (p=0.02); 2nd trimester: r=0.08 (p=0.09); and 3rd trimester: r=0.15 (p=0.001). When logistic regression was performed with preterm birth (<37 weeks) as the outcome and 25(OH)D quartiles as the predictor variable, adjusting for study and participant race/ethnicity, as with the correlation analysis, the measurements closer to delivery were more significantly associated and had a higher magnitude of effect. That is, at baseline, those who had serum concentrations <50nmol/L (20ng/mL) had 3.3 times of odds of a preterm birth compared to those with serum concentrations ≥100nmol/L (40ng/mL; p=0.27). At 2nd trimester, the odds were 2.0 fold (p=0.21) and at the end of pregnancy, the odds were 3.8 fold (p=0.01). The major findings from this exploratory analysis were: (1) maternal vitamin D status closest to delivery date was more significantly associated with preterm birth, suggesting that later intervention as a rescue treatment may positively impact the risk of preterm delivery, and (2) a serum concentration of 100nmol/L (40ng/mL) in the 3rd trimester was associated with a 47% reduction in preterm births. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Demonstration of a difference in urinary calcium, not calcium absorption, in black and white adolescents.

Bone mineral density (BMD) of the forearm, lumbar spine, and femoral neck is greater in black than in white children. Studies were performed to determine whether differences in intestinal absorption of calcium or urinary calcium or both account for an assumed more positive calcium balance and greater bone mass in black children. Normal black and white boys and girls were admitted to a metabolic ward and given a constant daily diet containing 1000 mg calcium, 60% as calcium carbonate, for 2 1/2 days (study I) or 3 1/2 days (study II). Fasting blood and 24 h urine collections were obtained, and in study II, unidirectional fractional absorption of calcium (alpha) was determined with stable isotopes of calcium. It was found that (1) serum 25-hydroxyvitamin D (25-OHD) and urinary calcium were lower and serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was higher in black than in white children, and (2) alpha was higher in boys than in girls with no racial difference, and (3) there were significant positive correlations between alpha and urinary calcium in the blacks and in the black and white children together. It is concluded that (1) alpha is higher in boys than in girls and (2) a lower urinary calcium, not increased intestinal absorption of calcium, is the means for a more positive calcium balance in blacks that accounts for the racial difference in BMD.