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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Osteopenia and Osteoporosis

(Last updated: February 12, 2014; last reviewed: February 12, 2014)


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Table 11j. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Osteopenia and Osteoporosis
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Osteopenia and Osteoporosis cART, especially following initiation and regardless of regimen

Specific Agents of Possible Concern
  • TDF 
  • d4T
  • PIs, especially LPV/r
Onset:
  • Any age; greatest risk in months after initiation of associated ARV
Presentation
  • Most commonly asymptomatic; fracture (rare)
  • Osteoporosis diagnosis in children requires clinical evidence of bone fragility (e.g., fracture with minimal trauma) and cannot rely solely on measured low BMD.
Low BMD:
  • 7% of a U.S. cohort had a BMD z score of  ≤ –2.0 (87% treated with cART).
  • 24% to 32% of Thai and Brazilian adolescents had a BMD z score of 
    ≤ –2.0 (92% to 100% treated with cART).

Longer duration of HIV infection Greater severity of HIV disease Growth delay, pubertal delay Low BMI Lipodystrophy Non-black race Smoking Corticosteroid use Medroxy-progesterone use Prevention:
  • Ensure sufficient calcium and vitamin D intake.
  • Encourage weight-bearing exercise.
  • Minimize modifiable risk factors (e.g., smoking, low BMI, steroid use).

Monitoring:

  • Assess nutritional intake (calcium, vitamin D, and total calories).
  • Obtain serum 25-OH-vitamin D.a
  • Obtain DXA.b
Ensure sufficient calcium and vitamin D intake. Encourage weight-bearing exercise. Reduce modifiable risk factors (e.g., smoking, low BMI, use of steroids, medroxyprogesterone). Role of bisphosphonates not established in children Consider change in ARV regimen.

a Some experts would periodically measure 25-OH-vitamin D, especially in HIV-infected urban youth because, in this population, the prevalence of vitamin D insufficiency is high.
b Until more data are available about the long-term effects of TDF on bone mineral acquisition in childhood, some experts would obtain a DXA at baseline and every 6 to 12 months for prepubertal children and children in early puberty who are initiating treatment with TDF. DXA should also be obtained in children with indications not uniquely related to HIV infection (such as cerebral palsy).

Key to Acronyms: ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; cART = combination antiretroviral therapy; d4T = stavudine; DXA = dual energy x-ray absorptiometry; LPV/r = lopinavir / ritonavir; PI = protease inhibitor; TDF = tenofovir disoproxil fumarate

References
Osteopenia and Osteoporosis

  1. McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. Oct 15 2010;51(8):937-946. Available at http://www.ncbi.nlm.nih.gov/pubmed/20839968.
  2. Mora S, Zamproni I, Beccio S, Bianchi R, Giacomet V, Vigano A. Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children. J Clin Endocrinol Metab. Jan 2004;89(1):24-28. Available at http://www.ncbi.nlm.nih.gov/pubmed/14715822.
  3. Hazra R, Gafni RI, Maldarelli F, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. Dec 2005;116(6):e846-854. Available at http://www.ncbi.nlm.nih.gov/pubmed/16291735.
  4. Gafni RI, Hazra R, Reynolds JC, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics. Sep 2006;118(3):e711-718. Available at http://www.ncbi.nlm.nih.gov/pubmed/16923923.
  5. Purdy JB, Gafni RI, Reynolds JC, Zeichner S, Hazra R. Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. Apr 2008;152(4):582-584. Available at http://www.ncbi.nlm.nih.gov/pubmed/18346519.
  6. Jacobson DL, Lindsey JC, Gordon CM, et al. Total body and spinal bone mineral density across Tanner stage in perinatally HIV-infected and uninfected children and youth in PACTG 1045. AIDS. Mar 13 2010;24(5):687-696. Available at http://www.ncbi.nlm.nih.gov/pubmed/20168204.
  7. Jacobson DL, Spiegelman D, Duggan C, et al. Predictors of bone mineral density in human immunodeficiency virus-1 infected children. J Pediatr Gastroenterol Nutr. Sep 2005;41(3):339-346. Available at http://www.ncbi.nlm.nih.gov/pubmed/16131991.
  8. Kalkwarf HJ, Zemel BS, Gilsanz V, et al. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab. Jun 2007;92(6):2087-2099. Available at http://www.ncbi.nlm.nih.gov/pubmed/17311856.
  9. Bachrach LK, Sills IN, Section on E. Clinical report-bone densitometry in children and adolescents. Pediatrics. Jan 2011;127(1):189-194. Available at http://www.ncbi.nlm.nih.gov/pubmed/21187316.
  10. Lima LR, Silva RC, Giuliano Ide C, Sakuno T, Brincas SM, Carvalho AP. Bone mass in children and adolescents infected with human immunodeficiency virus. Jornal de Pediatria. Jan-Feb 2013;89(1):91-99. Available at http://www.ncbi.nlm.nih.gov/pubmed/23544816.
  11. Puthanakit T, Saksawad R, Bunupuradah T, et al. Prevalence and risk factors of low bone mineral density among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy. J Acquir Immune Defic Syndr. Dec 1 2012;61(4):477-483. Available at http://www.ncbi.nlm.nih.gov/pubmed/22918157.
  12. Siberry GK, Li H, Jacobson D, Pediatric ACTGCS. Fracture risk by HIV infection status in perinatally HIV-exposed children. AIDS Res Hum Retroviruses. Mar 2012;28(3):247-250. Available at http://www.ncbi.nlm.nih.gov/pubmed/22471877.
  13. DiMeglio LA, Wang J, Siberry GK, et al. Bone mineral density in children and adolescents with perinatal HIV infection. AIDS. Jan 14 2013;27(2):211-220. Available at http://www.ncbi.nlm.nih.gov/pubmed/23032412.
  14. Bunders MJ, Frinking O, Scherpbier HJ, et al. Bone mineral density increases in HIV-infected children treated with long-term combination antiretroviral therapy. Clin Infect Dis. Feb 2013;56(4):583-586. Available at http://www.ncbi.nlm.nih.gov/pubmed/23097583.

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