Long-term consequences of HIV infection and its treatment appear to place the growing number of older HIV- infected adults at premature risk for disturbances of bone metabolism. HIV-infected adults are 3-4 times more likely to develop osteoporosis than their HIV-uninfected counterparts, and reported fracture rates are 30%-70% higher among HIV-infected persons. Body composition is an important factor in bone health, and body composition may be particularly affected in the setting of HIV infection as a result of the virus itself, specific antiretroviral drugs and restoration to health. HIV infection has been shown to differentially affect subcutaneous adipose tissue with greater decreases in the lower limbs. How this might affect bone health is unclear. Alterations in adipocyte differentiation in th lower limbs in the setting of HIV may affect bone metabolism. Some studies in HIV-uninfected persons suggest that fatty infiltration in the bone marrow (due to preferential differentiation fro a common marrow progenitor cell to adipocytes rather than osteoblasts) may lead to reduced bone formation, resulting in osteoporosis. While there is evidence that increased marrow fat, like low bone mineral density (BMD), predicts vertebral fracture in the elderly, and data suggest a relationship between increased marrow adiposity and bone loss, this area of investigation has been virtually unexplored in HIV- infected populations. Despite the high prevalence of disorders of bone and fat metabolism in HIV-infected individuals, little is known about how changes in regional body composition affect bone metabolism in this population. We propose: (1) To determine the relationship between regional fat changes and BMD among HIV- infected women compared with uninfected women;(2) To examine the relationship between adipokines and BMD in HIV-infected women;and (3) To conduct an exploratory investigation of the relationship between intravertebral marrow fat and BMD in HIV-infected women.
Aims 1 and 2 of the proposed study will leverage the existing and ongoing data collected as part of the largest cohort study of HIV-infected women in the United States, the Women's Interagency HIV Study (WIHS), and specifically HIV-infected and uninfected women participants of the WIHS Metabolic Substudy (WIHS MS), a prospective study which performs rigorous metabolic testing including DXA scans to quantify regional fat and bone density measurements.
Aim 3 will involve the collection of primary data in an exploratory investigation into bone marrow fat using magnetic resonance spectroscopy in a subset of WIHS MS women. The proposed study will allow the candidate to conduct high quality research in a timely and cost-effective manner, and examine the mechanism by which HIV-associated fat changes might affect bone loss in HIV-infected women.

Public Health Relevance

Long-term consequences of HIV infection and its treatment, particularly disturbances of bone metabolism, are emerging concerns given the growing numbers of older adults living with HIV. The proposed study examines how body fat alterations due to HIV infection and its treatment affect bone metabolism and explores the novel role of fatty infiltration of bone marrow in bone disease development. Identification of the mechanisms underlying these associations may have important implications for bone density screening and preventive interventions for reduced BMD in HIV-infected women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23AR061993-01A1
Application #
8410164
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Chen, Faye H
Project Start
2012-09-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
1
Fiscal Year
2012
Total Cost
$149,666
Indirect Cost
$11,086
Name
Suny Downstate Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
040796328
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Sharma, Anjali; Ma, Yifei; Scherzer, Rebecca et al. (2016) Brief Report: Association of Adipokines With Bone Mineral Density in HIV-Infected and HIV-Uninfected Women. J Acquir Immune Defic Syndr 73:433-437
Sharma, Anjali; Hoover, Donald R; Shi, Qiuhu et al. (2016) Falls among middle-aged women in the Women's Interagency HIV Study. Antivir Ther :
Scherzer, Rebecca; Lin, Haiqun; Abraham, Alison et al. (2016) Use of urine biomarker-derived clusters to predict the risk of chronic kidney disease and all-cause mortality in HIV-infected women. Nephrol Dial Transplant 31:1478-85
Baxi, Sanjiv M; Scherzer, Rebecca; Greenblatt, Ruth M et al. (2016) Higher tenofovir exposure is associated with longitudinal declines in kidney function in women living with HIV. AIDS 30:609-18
Weitzmann, M Neale; Ofotokun, Ighovwerha; Titanji, Kehmia et al. (2016) Bone Loss Among Women Living With HIV. Curr HIV/AIDS Rep 13:367-373
Sharma, Anjali; Flom, Peter L; Rosen, Clifford J et al. (2015) Racial differences in bone loss and relation to menopause among HIV-infected and uninfected women. Bone 77:24-30
Sharma, Anjali; Hoover, Donald R; Shi, Qiuhu et al. (2015) Relationship between Body Mass Index and Mortality in HIV-Infected HAART Users in the Women's Interagency HIV Study. PLoS One 10:e0143740
Sharma, Anjali; Shi, Qiuhu; Hoover, Donald R et al. (2015) Increased Fracture Incidence in Middle-Aged HIV-Infected and HIV-Uninfected Women: Updated Results From the Women's Interagency HIV Study. J Acquir Immune Defic Syndr 70:54-61
Jotwani, Vasantha; Scherzer, Rebecca; Abraham, Alison et al. (2015) Association of urine α1-microglobulin with kidney function decline and mortality in HIV-infected women. Clin J Am Soc Nephrol 10:63-73
Lang, Joshua; Scherzer, Rebecca; Tien, Phyllis C et al. (2014) Serum albumin and kidney function decline in HIV-infected women. Am J Kidney Dis 64:584-91

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