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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
  • Any age; greatest risk in months after initiation of associated ARV
  • 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).


  • 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

Osteopenia and Osteoporosis

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  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
  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
  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
  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

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