Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be
      expected for HIV-uninfected people of similar age, weight and race. As the majority of
      perinatally HIV-infected U.S. children are entering or in adolescence, the potential for
      HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular
      concern. The primary purpose of this study was to compare changes from pre-treatment levels
      of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in
      HIV-infected children and adolescents.
    

Detailed description: 
      Puberty is a time when the foundation is laid for healthy bone mass. Over the course of
      puberty, 26% of bone mass is established in the 4-year period of peak height velocity and up
      to 60% of adult peak bone mass is established. Factors that affect normal bone mineralization
      include calcium intake, vitamin D status, degree of physical and weight bearing activities,
      hormones, genetics, body weight, and general health and nutrition status. HIV-infected
      children, youth, and adults have lower bone mineral density (BMD) than would be expected for
      healthy people of similar age, weight, and race. As the majority of perinatally HIV-infected
      U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD
      during the adolescent peak of bone mass acquisition is of particular concern. The purpose of
      this study was to compare changes in BMD of the lumbar spine from pre-treatment levels to 24
      and 48 weeks after alendronate treatment or placebo in HIV-infected children and adolescents.

      Participants were randomized equally into one of three groups: Group 1A received alendronate
      for 96 weeks; Group 1B received alendronate for 48 weeks followed by placebo for 48 weeks;
      Group 2 received placebo for 48 weeks followed by alendronate for 48 weeks. All three groups
      were followed off treatment for an additional 48 weeks. Participants also received vitamin
      D/calcium for the duration of the study and were asked to perform 60 minutes of
      weight-bearing exercise each day.

      Clinic visits were scheduled every 12 weeks after entry, with telephone contact visits one,
      four, and 28 weeks after entry and the week 48 visit. A physical exam and dental assessment
      was conducted at each clinic visit, and a history of adverse events collected. Dual Energy
      X-ray absorptiometry (DXA), hematology and chemistry panels were conducted at entry and weeks
      24, 48, 72, 96 and 144. Lumbar spine and whole body (with head) BMD was measured using
      Hologic DXA scanners (QDR4500A, QDR4500W or Delphi A models).

      The primary analysis compared changes from entry to 24 and 48 weeks in lumbar spine BMD
      between Groups 1A and 1B combined (both on alendronate for initial 48 weeks) vs. Group 2 (on
      placebo for 48 weeks). Study participants were unblinded after 96 weeks of follow-up (the
      primary completion date) but remained on study, off study treatment, for an additional 48
      weeks.

      Secondary laboratory outcomes listed in the protocol (bone marker turnover and Receptor
      Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio) and central fat
      content, which required application for additional funding for laboratory testing, will not
      be performed and no results will be available.
    

Intervention name(s): Alendronate; Placebo; Calcium carbonate/vitamin D
Intervention type(s): Drug; Drug; Dietary Supplement
Intervention description(s): Oral tablet taken once weekly: 70 mg if participant greater than 30 kg or 35 mg if participant less than or equal to 30 kg; Oral tablet taken once weekly; Tablet taken once or twice daily: calcium carbonate (600 mg) and vitamin D (400 IU) once daily for participants with 25-OH-vitamin D levels greater than or equal to 20 ng/mL or twice daily for those with 25-OH-vitamin D levels less than 20 ng/mL
Other intervention name(s): Fosamax
Intervention MeSH terms: Vitamin D; Alendronate; Calcium Carbonate; Calcium
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Bone mineral density