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Osteoporosis International

, Volume 28, Issue 1, pp 201–209 | Cite as

Effect of high-dose cholecalciferol (vitamin D3) on bone and body composition in children and young adults with HIV infection: a randomized, double-blind, placebo-controlled trial

  • A. J. Rovner
  • V. A. Stallings
  • R. Rutstein
  • J. I. Schall
  • M. B. Leonard
  • B. S. ZemelEmail author
Original Article

Abstract

Summary

It is unknown whether vitamin D supplementation positively impacts body composition and bone outcomes in children and young adults with HIV. This RCT found that despite increasing 25(OH)D concentrations, high dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection.

Introduction

The objective of this paper was to determine the impact of high-dose daily cholecalciferol (vitamin D3) supplementation on body composition and bone density, structure, and strength in children and young adults with perinatally acquired (PHIV) or behaviorally acquired (BHIV) HIV infection.

Methods

Participants were randomized to receive vitamin D3 supplementation (7000 IU/day) or placebo for 12 months. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, dual energy X-ray absorptiometry (DXA) of the whole body and lumbar spine, and peripheral quantitative computed tomography (pQCT) of tibia sites were acquired at 0, 6, and 12 months. DXA and pQCT outcomes were expressed as sex- and population-ancestry specific Z-scores relative to age and adjusted for height or tibia length, as appropriate.

Results

Fifty-eight participants (5.0 to 24.9 years) received vitamin D3 supplements (n = 30) or placebo (n = 28). At enrollment, groups were similar in age, sex, population ancestry, growth status, serum 25(OH)D concentrations, body composition, and size-adjusted bone measures. Median 25(OH)D concentrations were similar (17.3 ng/mL in the vitamin D3 supplementation group vs 15.6 ng/mL in the placebo group), and both groups had mild bone deficits. At 12 months, 25(OH)D rose significantly in the vitamin D supplementation group but not in the placebo group (26.4 vs 14.8 ng/mL, respectively, p < 0.008). After adjusting for population ancestry, sex, antiretroviral therapy use, and season, there were no significant treatment group differences in bone or body composition outcomes.

Conclusions

Despite increasing 25(OH)D concentrations, 12 months of high-dose vitamin D3 supplementation did not impact bone or body composition in children and young adults with HIV infection.

Keywords

Cholecalciferol Dual energy X-ray absorptiometry HIV Peripheral quantitative computed tomography 

Notes

Acknowledgements

We are grateful to the study participants and their families. We would like to thank Julia L. Samuel and Savannah Knell, as the lead study staff members. In addition, we would like to acknowledge the Clinical Translational Research Center, the Special Immunology Family Care Clinic, Adolescent Initiative Program at CHOP, Jonathan Lax Treatment Center, Cooper University Hospital, Alfred I. duPont Hospital for Children, Hospital of the University of Pennsylvania, Temple University Hospital, and Drexel University Hospital.

Funding

This work was supported by the NIH/National Center for Complementary and Alternative Medicine, Grant R01AT005531, the National Center for Research Resources, Grant UL1RR024134, and is now at the National Center for Advancing Translational Sciences, Grant UL1TR000003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This publication was made possible through core services and support from the University of Pennsylvania Center for AIDS Research, an NIH-funded program (P30AI045008). Additional support was from the Jean A. Cortner Endowed Chair, Nutrition Center and the Research Institute at the Children’s Hospital of Philadelphia. Life Extension (Ft. Lauderdale, FL) and J.R. Carlson Laboratories, Inc. (Arlington Heights, IL) donated the vitamin D3 supplements and placebo capsules and drops, respectively.

Compliance with ethical standards

Conflicts of interest

None.

References

  1. 1.
    Puthanakit T, Silberry GK (2013) Bone health in children and adolescents with perinatal HIV infection. J Int AIDS Soc 16:18575CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Arpadi SM, Horlick MN, Wang J, Cuff P, Bamji M, Kotler DP (1998) Body composition in prepubertal children with human immunodeficiency virus type 1 infection. Arch Pediatr Adolescent Med 152(7):688–693CrossRefGoogle Scholar
  3. 3.
    Miller TL, Evans SJ, Orav EJ, Morris V, McIntosh K, Winter HS (1993) Growth and body composition in children infected with the human immunodeficiency virus-1. Am J Clin Nutr 57(4):588–592PubMedGoogle Scholar
  4. 4.
    Guaraldi G, Stentarelli C, Zona S, Santoro A (2013) HIV-associated lipodystrophy: impact of antiretroviral therapy. Drugs 73:1431–1450CrossRefPubMedGoogle Scholar
  5. 5.
    Loomba-Albrecht LA, Bregman T, Chantry CJ (2014) Endocrinopathies in children infected with human immunodeficiency virus. Endocrinol Metab Clin N Am 43(3):807–828CrossRefGoogle Scholar
  6. 6.
    O’Brien KO, Henderson RA, Caballero B, Ellis KJ (2001) Bone mineral content in girls perinatally infected with HIV. Am J Clin Nutr 73(4):821–826PubMedGoogle Scholar
  7. 7.
    Stephensen CB, Marguis GS, Kruzich LA, Douglas SD, Aldrovandi GM, Wilson CM (2006) Vitamin D status in adolescents and young adults with HIV infection. Am J Clin Nutr 83(5):1135–1141PubMedGoogle Scholar
  8. 8.
    Villamore E (2006) A potential role for vitamin D on HIV infection? Nutr Rev 64(5 Pt 1):226–233CrossRefGoogle Scholar
  9. 9.
    Eckard AR, Tangpricha V, Seydafkan S, O'Riordan MA, Storer N, Labbato D, McComsey GA (2013) The relationship between vitamin D status and HIV-related complications in HIV-infected children and young adults. Pediatr Infect Dis J 32(11):1224–1229CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chao D, Rutstein RM, Steenhoff AP, Shanbhag M, Andolaro K, Zaoutis T (2003) Two cases of hypocalcemia secondary to vitamin D deficiency in an urban HIV-positive pediatric populuation. AIDS 17(16):2401–2403CrossRefPubMedGoogle Scholar
  11. 11.
    Arpadi SM, McMahon D, Abrams EJ, Bamji M, Purswani M, Engelson ES, Horlick M, Shane E (2009) Effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents. Pediatrics 123(1):e121–e126CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rutstein R, Downes A, Zemel B, Schall J, Stallings V (2011) Vitamin D status in children and young adults with perinatally acquired HIV infection. Clin Nutr 30(5):624–628CrossRefPubMedGoogle Scholar
  13. 13.
    Mateo L, Holgado S, Marinoso ML, Perez-Andres R, Bonjoch A, Romeu J, Oilve A (2014) Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients. Clin Rheumatol. Epub ahead of printGoogle Scholar
  14. 14.
    Lucey JM, Hsu P, Ziegler JB (2013) Tenofovir-related Fanconi's syndrome and osteomalacia in a teenager with HIV. BMJ Case Report.;9Google Scholar
  15. 15.
    Jacobson DL, Spiegelman D, Duggan C, Weinberg GA, Bechard L, Furuta L, Nicchitta J, Gorbach SL, Miller TL (2005) Predictors of bone mineral density in human immunodeficiency virus-1 infected children. J Pediatr Gastroenterol Nutr 41(3):339–346CrossRefPubMedGoogle Scholar
  16. 16.
    Sentongo TA, Rutstein R, Stettler N, Stallings VA, Rudy B, Mulberg AE (2001) Association between steatorrhea, growth and immunological status in children with perinatally acquired HIV infection. Arch Pediatr Adol Med 155:149–153CrossRefGoogle Scholar
  17. 17.
    Aurpibul L, Puthanakit T (2014) Review of tenofovir use in HIV-infected children. Pediatr Infect Dis J 22Google Scholar
  18. 18.
    World Health Organization (2012) Use of Tenofovir in HIV-Infected Children and Adolescents: A Public Health Perspective. Geneva, SwitzerlandGoogle Scholar
  19. 19.
    Arpadi SM, Horlick M, Thornton J, Cuff PA, Wang J, Kotler DP (2002) Bone mineral content is lower in prepubertal HIV-infected children. J Acquir Immune Defic Syndr 29(5):450–454CrossRefPubMedGoogle Scholar
  20. 20.
    DiMeglio LA, Wang J, Siberry GK, Miller TL, Geffner ME, Hazra R, Borkowsky W, Chen JS, Dooley L, Patel K, van Dyke RB, Fielding RA, Gurmu Y, Jacobson DL, Pediatric HIVAIDS Cohort Study (PHACS) (2013) Bone mineral density in children and adolescents with perinatal HIV infection. AIDS 27(2):211–220CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mora S, Zamproni I, Beccio S, Bianchi R, Giacomet V, Viganò A (2004) Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children. J Clin Endocrinol Metab 89(1):24–28CrossRefPubMedGoogle Scholar
  22. 22.
    Stallings VA, Schall J, Hediger ML, Zemel BS, Tuluc F, Dougherty KA, Samuel JL, Rutstein RM (2015) High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial. Pediatr Infect Dis J 34(2):e32–40Google Scholar
  23. 23.
    Havens PL, Mulligan K, Hazra R, Flynn P, Rutledge B, Van Loan MD, Lujan-Zilbermann J, Kapogiannis BG, Wilson CM, Stephensen CB (2012) Adolescent medicine trials network for HIV/AIDS interventions (ATN) 063 study team. Serum 25-hydroxyvitamin D response to vitamin D3 supplementation 50,000 IU monthly in youth with HIV-1 infection. J Clin Endocrinol Metab 97(11):4004–4013CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Arpadi SM, McMahon D, Abrams EJ, Bamji M, Purswani M, Engelson ES, Horlick M, Shane E (2012) Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrural in HIV-infected children and adolescents: a randomized clinical trial. Am J Clin Nutr 95:678–685CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dougherty K, Schall J, Zemel B, Tuluc F, Hou X, Rutstein R, Stallings V (2014) Safety and efficacy of high dose daily vitamin D3 supplementation in children and young adults infected with HIV. J Pediatr Infect Dis Soc 3(4):294–303CrossRefGoogle Scholar
  26. 26.
    (2016) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretorviral Agents in Pediatric HIV Infection. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Accessed June 5, 2016 [pages 38–39, Table 12j. Antiretroviral-Therapy-Associated Adverse Effects and Management Recommendations—Osteopenia and Osteoporosis]
  27. 27.
    Caldwell MB, Oxtoby M, Simonds RJ, Lindegren ML, Rogers MF (1994) Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Recommendations and Reports, AtlantaGoogle Scholar
  28. 28.
    Castro KG, Ward J, Slutsker L, Buehler JW, Jaffe HW, Berkelman RL et al (1992) Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recommendations and Reports, AtlantaGoogle Scholar
  29. 29.
    Lohman TG, Roche A, Martorell R (1988) Anthropometric standardization reference manual. Human Kinetics Publishes Inc, ChampaignGoogle Scholar
  30. 30.
    Morris NM, Udry J (1980) Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adol 9:271–280CrossRefGoogle Scholar
  31. 31.
    Ferretti JL, Capozza R, Zanchetta JR (1996) Mechanical validation of a tomographic (pQCT) index for noninvasive estimation of rat femur bending strength. Bone 18(2):97–102CrossRefPubMedGoogle Scholar
  32. 32.
    Sievanen H, Koskue V, Rauhio A, Kannus P, Heinonen A, Vuori I (1998) Peripheral quantitative computed tomography in human long bones: evaluation of in vitro and in vivo precision. J Bone Miner Res 13(5):871–882CrossRefPubMedGoogle Scholar
  33. 33.
    Braun MJ, Meta M, Schneider P, Reiners C (1998) Clinical evaluation of a high-resolution new peripheral quantitative computerized tomography (pQCT) scanner for the bone densitometry at the lower limbs. Phys Med Biol 43(8):2279–2294CrossRefPubMedGoogle Scholar
  34. 34.
    Ogden CL, Kuczmarski R, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL (2002) Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109:45–60CrossRefPubMedGoogle Scholar
  35. 35.
    Weber DR, Moore R, Leonard MB, Zemel BS (2013) Fat and lean BMI reference curves in children and adolescents and their utility in identifying excess adiposity compared with BMI and percentage body fat. Am J Clin Nutr 98(1):49–56CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Zemel BS, Leonard M, Kelly A, Lappe JM, Gilsanz V, Oberfield S, Mahboubi S, Shepherd JA, Hangartner TN, Frederick MM, Winer KK, Kalkwarf HJ (2010) Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 95(3):1265–1273CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    (2002) LMS program version 1.16 compiled 15 April 2002 [computer program]. Version 1.162002.Google Scholar
  38. 38.
    Cole TJ, Green PJ (1992) Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 11(10):1305–1319CrossRefPubMedGoogle Scholar
  39. 39.
    Leonard MB, Elmi A, Mostoufi-Moab S, Schults J, Burnham JM, Thayu M, Kibe L, Wetzsteon RJ, Zemel BS (2010) Effects of sex, race, and puberty on cortical bone and the functional muscle bone unit in children, adolescents, and young adults. J Clin Endocrinol Metab 95(4):2009–2013CrossRefGoogle Scholar
  40. 40.
    Kumar J, Munther P, Kaskei FJ, Hailern SM, Melamed ML (2009) Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics 124(3):e362–e370CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Crabtree N, Arabi A, Bacharch LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH et al (2013) Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD pediatric official positions. J Clin Densitom 17(2):225–242CrossRefGoogle Scholar
  42. 42.
    Williams PL, Abzug M, Jacobson DL, Wang J, Van Dyke RB, Hazra R, Patel K, Dimeglio LA, McFarland EJ, Silio M, Borkowsky W, Seage GR 3rd, Oleske JM, Geffner ME (2013) International maternal pediatric and adolescent AIDS clinical trials P219219C study and the Peidatric HIV/AIDS cohort study. Pubertal onset in children with perinatal HIV infection in the era of combination antiretorival treatment. AIDS 27(12):1959–1970CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Institute of Medicine (2010) Dietary Reference Intakes for Calcium and Vitamin D. Washington, DCGoogle Scholar
  44. 44.
    Golden NH, Abrams S (2014) And committee on nutrition. Optimizing bone health in children and adolescents. Pediatrics 134(4):e1229–e1243CrossRefPubMedGoogle Scholar
  45. 45.
    Zuccotti G, Vigano A, Gabiano C, Giacomet V, Mignone F, Stucchi S, Manfredi V, Marinacci F, Mora S (2010) Antiretroviral therapy and bone mineral measurements in HIV-infected youths. Bone 46:1633–1638CrossRefPubMedGoogle Scholar
  46. 46.
    Kelly TL, Wilson KE, Heymsfield SB (2009) Dual energy X-ray absorptiometry body composition reference values from NHANES. PLoS One 4(9):e7038CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  • A. J. Rovner
    • 1
  • V. A. Stallings
    • 1
  • R. Rutstein
    • 2
  • J. I. Schall
    • 1
  • M. B. Leonard
    • 3
  • B. S. Zemel
    • 1
    Email author
  1. 1.Division of Gastroenterology, Hepatology and NutritionThe Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  2. 2.General Pediatrics, Department of PediatricsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of NephrologyStanford UniversityStanfordUSA

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