Short-term effect of testosterone treatment on reduced bone density in boys with constitutional delay of puberty

We studied bone mineral content (BMC), bone mineral density (BMD), cortical thickness/total width (CT/TW) ratio and cortical area/total area (CA/TA) ratio in boys with constitutional delay of puberty and the effect of short-term testosterone treatment on bone mass. Seventeen boys (age 13.1-15.8 years) who met the family history and the clinical criteria of constitutional delay of puberty were selected and enrolled in the study. All subjects were eating a diet assuring an adequate intake of calories and calcium. A subset of 8 boys (group A) was treated with testosterone depot (100 mg/month x 6 months) while 9 boys (group B) were not. At inclusion, BMC and BMD were reduced in the patients according to their chronological age (BMC -4.04 +/- 1.34 standard deviation scores [SDS]; BMD -2.95 +/- 0.56 SDS), statural age (BMC -1.75 +/- 0.79 SDS; BMD -1.69 +/- 0.78 SDS), and bone age (BMC -1.80 +/- 0.65 SDS; BMD -1.86 +/- 0.68 SDS). No significant differences between the groups were found (group A: BMC 0.480 +/- 0.57 g/cm, BMD 0.488 +/- 0.037 g/cm2, CT/TW ratio 0.43 +/- 0.4, CA/TA ratio 0.68 +/- 0.04; group B: BMC 0.476 +/- 0.060, p = NS vs. group A; BMD 0.491 +/- 0.036 g/cm2, p = NS vs. group A). At 12 months of follow-up, BMC, BMD, CT/TW ratio, and CA/TA ratio significantly increased in group A (BMC 0.70 +/- 0.13 g/cm, delta +41.1 +/- 28.8%, p < 0.003 vs. 0 month; BMD 0.617 +/- 0.082 g/cm2, delta +26.2 +/- 13.6%, p < 0.005 vs. 0 month; CT/TW ratio 0.52 +/- 0.05, delta +20.59 +/- 10.65%, p < 0.001 vs. 0 month; CA/TA ratio 0.77 +/- 0.05 vs. 0 month; CT/TW ratio 13.60 +/- 6.65%, p < 0.004 vs 0 month), but not in group B (BMC: 0.48 +/- 0.05 g/cm; delta +5.1 7.8%, p = NS vs. 00 month; BMD: 0.492 +/- 0.037 g/cm2; delta +0.54 +/- 8.7%, p = NS vs. 0 month; CT/TW ratio 0.44 +/- 0.04, delta +4.04 +/- 6.75%, p = NS vs. 0 month; CA/TA ratio 0.68 +/- 0.05, delta +2.39 +/- 5.90%, p = NS vs. 0 month). We conclude that boys with constitutional delay of puberty have reduced BMC and BMD. The delay in statural and bone ages did not totally account for the decreased bone mass. Testosterone treatment for 6 months significantly increased BMC, BMD, CT/TW ratio, and CA/TA ratio in these patients, but definitive conclusions on the efficacy of the treatment in improving adult bone mass can be drawn only when our patients reach early childhood.     

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.