Effect of HIV Infection and Highly Active Antiretroviral Treatment (HAART) on Bone Homeostasis (OPG-2)
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|ClinicalTrials.gov Identifier: NCT01020045|
Recruitment Status : Completed
First Posted : November 25, 2009
Last Update Posted : October 19, 2015
Advances in HAART have been a huge success story in the management of HIV infection. However, serious metabolic complications including osteoporosis and bone fractures are increasingly been seen with HAART, and the responsible mechanisms remain poorly elucidated.
The skeleton continually regenerates through homeostatic bone remodeling. Osteoclasts the cells responsible for bone resorption form under the influence of the key osteoclastogenic cytokine Receptor- Activator of NF-KB (RANKL). The osteoclastogenic and pro-resorptive activities of RANKL are moderated by its physiological decoy receptor osteoprotegerin (OPG). Increase in the ratio of RANKL to OPG accelerates the rate of osteoclastic bone resorption leading to osteoporosis.
The investigators' preliminary studies have now demonstrated that in an animal model of HIV/AIDS, the HIV-1 Transgenic rat, the development of osteoporosis is recapitulated as observed in human patients. Furthermore, the investigators found that B cell expression of OPG is significantly downregulated, concurrent with a significant upregulation in production of RANKL.
|Condition or disease|
|HIV Infection Osteopenia Osteoporosis|
The investigators hypothesize that "immunological disruption of B cell number and/or function, may play a key causal role in the bone loss associated with HIV/AIDS, by driving a "switch" from OPG production to overproduction of RANKL". The investigators propose to determine the role of perturbations in B and T cells on OPG and RANKL production and on bone turnover.
This is a cross-sectional analysis of changes in BMD (DXA), and B cell and T cell function in HIV seronegative/seropositive subjects matched by known risk factors for osteoporosis. Serum will be collected for quantitation of total OPG and RANKL, and for biochemical markers of bone turnover (CTx, and TRAP5b), specific and sensitive markers of osteoclast activity, and for osteocalcin and P1NP, specific and sensitive markers of bone formation by commercial ELISAs. Peripheral blood mononuclear cells (PBMC) will be isolated and total and percentage frequency and absolute number (/mL) of B cells (CD19+) and T cells (CD3) and their subsets (CD4 and CD8). B cells (CD19) and T cells (CD3 and CD4 and CD8) will be immunomagnetically purified and OPG and RANKL mRNA and protein production quantitated by RT-PCR and ELISA respectively. As a secondary endpoint, B cells will be fractionated into subsets based on differential expression of the markers CD10, CD21 and CD27 and OPG and RANKL production quantitated by in each subset by intracellular staining and FACS analysis.
|Study Type :||Observational|
|Actual Enrollment :||120 participants|
|Official Title:||Effect of HIV Infection and HAART on Bone Homeostasis|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||October 2015|
HIV-seropositive, HIV seronegative
No intervention - biologic samples were collected from both HIV positive and HIV negative subjects
Treatment naive subjects
HIV-seropositive subjects naive to antiretroviral therapy. HIV-seronegative subjects otherwise healthy.
- To correlate serum and B cell and T cell OPG and/or RANKL production in treatment-naïve HIV-infected patients, with indices of bone turnover and structure and with viral load. [ Time Frame: During entry visit ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01020045
|United States, Georgia|
|Grady Infectious Diseases Program Clinic|
|Atlanta, Georgia, United States, 30308|
|Principal Investigator:||Ighovwerha Ofotokun, MD, MSc||Emory University|