icon-    folder.gif   Conference Reports for NATAP  
 
  18th CROI
Conference on Retroviruses
and Opportunistic Infections
Boston, MA
February 27 - March 2, 2011
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The Effect of Bimonthly Supplementation with Oral Cholecalciferol and Calcium on 2 Year Bone Mass Accrual in HIV-infected Children and Adolescents
 
 
  Reported by Jules Levin
CROI 2011 Boston Msrch 2
 
Stephen Arpadi1246, Donald McMahon3, Elaine J. Abrams45, Marukh Bamji7, Murli Purswani8, Ellen S. Engelson36, Mary Horlick9, Elizabeth Shane3 College of Physicians & Surgeons, Columbia University -- 1G.H. Sergievsky Center, 2Department of Pediatrics, 3Department of Medicine, New York, NY, US ~ 4Mailman School of Public Health, Columbia University, New York, NY, US ~ 5Harlem Hospital Center, New York, NY, US ~ 6Center for Comprehensive Care, St. Luke's-Roosevelt Hospital Center, New York, NY, US ~ 7Metropolitan Hospital Center, New York, NY, US ~ 8Bronx-Lebanon Hospital Center, Bronx, NY, US ~ 9National Institutes of Health - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, US
 
"Vitamin D (100,000 IU every two months) and calcium (1000 mg/day) supplementation of a group of HIV-infected children and adolescents with baseline serum [25(OH)D] <30 ng/ml was associated with an increase in mean serum [25(OH)D] levels into an optimal bone health range (>30 ng/ml). At baseline. Although the VD+/Ca+ supplement achieved a mean serum concentration of 25-OH D above 30 ng/ml, 75% in this arm had at least one monthly 25-OH D concentration below 30 ng/ml. Thus, a possible explanation for our findings is a failure to maintain concentrations of 25-OH D above 30ng/ml. Poor adherence to daily calcium supplements might also have contributed to the lack of improvement. Serum 25-OHD (ng/ml) mean vitamin d and clcium were 24.1 9.1 in the patients receiving vitamin d and calcium supplementation and 23.6 10.2 in the placebo group..... On average, study participants randomized to VD+/Ca+ weighed less and had lower weight-for-age than the double placebo group, and were not as advanced with respect to level of sexual maturation though none of these differences were statistically significant."
 
AUTHOR CONCLUSIONS

 
Vitamin D (100,000 IU every two months) and calcium (1000 mg/day) supplementation of a group of HIV-infected children and adolescents with baseline serum [25(OH)D] <30 ng/ml was associated with an increase in mean serum [25(OH)D] levels into an optimal bone health range (>30 ng/ml).
 
Despite the increase of serum 25(OH)D we did not detect a significant effect on either whole body or spine bone mass accrual.
 
In subjects with rapid pubertal advancement, there was a larger increase in TBBMC and SBMC in those randomized to VD+/Ca+; however, the difference was not significant.
 
Total body bone mineral content and densit (TBBMC and TBBMD) and spine bone mineral content and density (SBMC and SBMD)
 
Our small study sample size imposes limitations with respect to power to detect differences in bone mass accrual between the intervention and control goups. The sample is inadequate for discerning the complex interaction of age, sexual maturation and bone mass accrual in children and adolescents undergoing sexual maturation.
 
Future studies of vitamin D and calcium should consider greater frequency of vitamin D dosing to achieve more sustained concentrations of 25(OH)D.
 
Future study designs should also account for variability of bone mass acquisition related to sexual maturation.
 
Mean concentration of 25(OH)D among subjects receiving VD+/Ca+ and those receiving VD-/Ca- by month of study.
 
· The mean [25(OH)D] were significantly different between the two groups at 1 and 2 years.
 
· Fewer subjects in the VD+/Ca+ group had a [25(OH)D] ≤20 ng/mL (inadequate), 30 vs 75%, p=.0004.
 
· More subjects in the VD+/Ca+ group achieved [25(OH)D] >30 ng/mL (adequate), 69 vs 42%, p=.06.
 

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INTRODUCTION
 
· Skeletal abnormalities, including decreased bone mineral content (BMC) and bone mineral density (BMD), are among the morbidities recognized in HIV-infected youth.
 
· While anti-retroviral medications are implicated, vitamin D deficiency, which is highly prevalent, may also contribute to altered bone metabolism.
 
· Although repletion of vitamin D has the potential to improve bone mass acquisition in children or adolescents with HIV, it has not been evaluated.
 
· We recently reported that bimonthly supplementation with 100,000 IU of cholecalciferol results in significant increases in serum 25(OH)D levels in HIV-infected youth over 1 year (Arpadi S et al. The effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents. Pediatrics. 2009;123:e121).
 
· The aim of this study is to determine whether supplementation with vitamin D and calcium for 2 years results in increased bone mass accrual.
 
· Our hypothesis was that bone accrual would be enhanced by supplementation with vitamin D and calcium.
 
ABSTRACT
 
Background: Decreased bone mineral content and bone mineral density are reported in HIV- infected children and adolescents. While the etiology is not well understood, vitamin D deficiency, a highly prevalent condition in children and adolescents with HIV may be involved. Objective: To evaluate the effect of oral cholecalciferol, 100,000 IU every 2 months with 1 gram daily of calcium on 2 year bone mass accrual in HIV infected children and adolescents.
 
Design: Perinatally HIV-infected children and adolescents, aged 6-16 years were randomized to receive vitamin D (100,000 IU bi-monthly) and calcium (1 g daily) (VD+/Ca+; n=30) or double placebo (VD-/Ca-; n=29) for 2 years. Total body (TBBMC) and spine bone mineral content (SBMC) by DXA and Tanner stage were assessed at baseline and 2 annual follow-up visits. 25-OHD concentrations were measured bimonthly.
 
Results: At enrollment the VD+/Ca+ and VD-/Ca- groups did not differ with respect to age, gender, dietary intake of vitamin D and calcium, baseline 25-OH D, or TBBMC,TBBMC z- score, TBBMD, TBBMD z-score SBMC, SBMC z-score or SBMD. The mean 25-OH D were significantly different between the VD+/Ca+ and VD-/Ca- groups at 1 and 2 years, 34.9 (8.9) vs 22.4 (9.8) ng/mL, p<0.001 and 38.6 (10.6) vs 26.2 (11.9) ng/mL, p<0.001, respectively. Significant increases in TBBMC, TBMD, SBMMC, and SBMD at 1 and 2 year were observed in both groups; however no differences between groups were seen at any time point. No differences between the 1 or 2 year changes in any of the bone mass parameters were observed between the intervention and control groups when analyses adjusting for weight, height, stage of sexual maturation were performed by linear mixed model analysis.
 
Conclusions: Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100,000 IU every 2 months, together with one gram daily of calcium, did not result in differential improvement in bone mass accrual. Although the VD+/Ca+ supplement achieved a mean serum concentration of 25-OH D above 30 ng/ml, 75% in this arm had at least one monthly 25-OH D concentration below 30 ng/ml. Thus, a possible explanation for our findings is a failure to maintain concentrations of 25-OH D above 30ng/ml. Poor adherence to daily calcium supplements might also have contributed to the lack of improvement.
 

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Characteristics of subjects receiving VD+/Ca+ and those receiving VD-/Ca-at time of enrollment.
 
On average, study participants randomized to VD+/Ca+ weighed less and had lower weight-for-age than the double placebo group, and were not as advanced with respect to level of sexual maturation though none of these differences were statistically significant.

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