Effect of HIV Infection and Highly Active Antiretroviral Treatment (HAART) on Bone Homeostasis (OPG-2)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01020045 |
Recruitment Status
:
Completed
First Posted
: November 25, 2009
Last Update Posted
: October 19, 2015
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
Observational Model: | Cohort |
Time Perspective: | Cross-Sectional |
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 |
Group/Cohort |
---|
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 ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- Healthy (sero-negative) volunteers and otherwise healthy treatment naïve HIV-1 sero-positive patient.
- Age >30<50 years and segregated into age and gender ranges as described above in section 3.2 (15 subjects per stratification based on Power Test).
- Ability and willingness of subject or legal guardian/representative to give written informed consent.
- Antiretroviral naivety.
- No CD4 T-cell counts requirement.
-
Absence of non-HIV related active immunological or bone disorders such as;
- Bone marrow or organ transplantation
- Inflammatory bowel disease (ulcerative colitis, crohn's disease)
- Multiple Myeloma
- Osteogenesis imperfect
- Osteomalacia
- Osteosarcoma
- Paget's disease
- Postmenopausal osteoporosis
- Rheumatoid arthritis
- Systemic lupus erythematosus
-
Laboratory values obtained within 90 days prior to study entry:
- Hemoglobin >9.4 g/dl
- Creatinine < 2 mg/dl
- AST (SGOT) < 2 x ULN
- ALT (SGPT) < 2 x ULN
Exclusion Criteria:
- Physical or biochemical evidence or a medical history of malignancy.
- Currently (within the past 8 weeks) taking any medication with known influence on the immune or skeletal system (e.g. immune modulation therapy, glucocorticoids, steroid hormones, bisphosphonates).
- The patient is not fully ambulatory.
- Pregnancy or breast feeding.
Exclusion criteria are primarily centered on immunological aspects with bone related aspects secondary. This is because in our model immunological function is proximal to bone function. Consequently, use of vitamin D or calcium supplementation will not be exclusion criteria, but will be added as covariates in our analysis.

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 |
Additional Information:
Publications of Results:
Responsible Party: | Ighovwerha Ofotokun, Associate Professor of Medicine, Emory University |
ClinicalTrials.gov Identifier: | NCT01020045 History of Changes |
Other Study ID Numbers: |
IRB00027210 R01AR059364-01 ( U.S. NIH Grant/Contract ) |
First Posted: | November 25, 2009 Key Record Dates |
Last Update Posted: | October 19, 2015 |
Last Verified: | October 2015 |
Keywords provided by Ighovwerha Ofotokun, Emory University:
HIV Osteopenia Osteoporosis |
Additional relevant MeSH terms:
Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome Osteoporosis Bone Diseases, Metabolic Lentivirus Infections Retroviridae Infections RNA Virus Infections |
Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Bone Diseases Musculoskeletal Diseases Metabolic Diseases |