Safety and Effectiveness of Oral Alendronate Therapy on Bone Mineral Density in HIV-infected Children and Adolescents With Low Bone Mineral Density

• Pre-treatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment versus placebo, as measured by Hologic bone densitometers [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  
• Safety of of alendronate use as measured by the incidence of new hematology or chemistry laboratory values greater than or equal to Grade 3; signs or symptoms; or new cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  

• Changes from pre-treatment levels of whole body BMD after alendronate treatment versus placebo [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  
• Changes from pre-treatment levels of whole body and lumbar spine BMD alendronate treatment versus 48 weeks of alendronate followed by 48 weeks of placebo [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  
• Effect of other known bone mineral determinants (age, gender, race/ethnicity, steroid use, Depo-Provera, tenofovir, pubertal stage, bone age, vitamin D status) and inflammatory cytokine levels on changes in BMD after alendronate treatment [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  
• Changes in BMD after completion of 48 weeks of alendronate therapy [ Time Frame: At Weeks 48 and 96 ] [ Designated as safety issue: No ]
  
• Alterations in pre-treatment bone marker turnover, receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANKL/OPG) ratio, central fat content, and determination of whether the changes in these outcomes correlate with changes in BMD [ Time Frame: At study entry and Week 48 ] [ Designated as safety issue: No ]
  
• Effect of alendronate therapy on changes in HIV status (as measured by changes in viral load, CD4% and CDC disease category) and determination whether the changes in these outcomes correlate with changes in BMD [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Duration of detectable urinary alendronate in adolescent participants who have completed 48 and 96 weeks of alendronate therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

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 is to compare changes from pretreatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in HIV-infected children and adolescents.

This study will last approximately 144 weeks. Participants will be randomized into one of three groups.

Participants in Group 1 will receive alendronate for 96 weeks. Participants in Group 2 will receive alendronate for 48 weeks and alendronate placebo for an additional 48 weeks. Participants in Group 3 will receive placebo for 48 weeks followed by alendronate for 48 weeks. All three groups will be followed off treatment for an additional 48 weeks. All participants will receive vitamin D/calcium for the duration of the study.

There will be 13 study visits for each participant. They will occur at study entry and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144. A physical exam, targeted events history, and adherence questionnaire will occur at all visits. Blood and urine collection, Tanner stage assessment, DXA scan, and radiograph will occur at most visits. Participants will also complete a questionnaire about smoking behavior at screening. Participants will be contacted by telephone 7 times throughout the study at Weeks 1, 4, 28, 49, 52, 76, and 100 to screen for adverse events, assess adherence, and reinforce study instructions.

Information provided by adolescent participants about sexual activity, pregnancy, and smoking and alcohol use will not be shared without the participants' permission.