Open Access Open Badges Research

Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients

Lidia Gazzola1, Giusi Maria Bellistri1, Camilla Tincati1, Valentina Ierardi1, Alessia Savoldi1, Angelo Del Sole2, Luca Tagliabue2, Antonella d’Arminio Monforte1 and Giulia Marchetti1*

Author Affiliations

1 Department of Health Sciences, Clinic of Infectious Diseases, “San Paolo” Hospital, University of Milan, Via A. Di Rudinì, 8, Milan, 20142, Italy

2 Department of Biomedical Sciences and Technologies and Center of Molecular and Cellular Imaging, “San Paolo” Hospital, University of Milan, Milan, Italy

For all author emails, please log on.

Journal of Translational Medicine 2013, 11:51  doi:10.1186/1479-5876-11-51

Published: 28 February 2013



HIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence.


Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-score < -1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with p < .05 were evaluated by multivariate logistic regression.


78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADR + CD4+ and CD8+ (p = .03 and p = .002, respectively). Interestingly, no differences in senescent CD28-CD57 + CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4 + CD28- phenotype (p = .04) at the advantage of the CD28+ pool (p = .03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.

Activated HLADR + CD4+/CD8+ and CD28 + CD4+ cells were independently associated with impaired BMD (AOR = 1.08 for each additional HLADR + CD4+ percentage higher; CI 95%,1.01-1.15; p = .02; AOR = 1.07 for each additional HLADR + CD8+ percentage higher; CI 95%,1.01-1.11; p = .01; AOR = 1.06 for each additional CD28 + CD4+ percentage higher; CI 95%,1.0-1.13; p = .05).


Heightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.

Osteopenia; Osteoporosis; Bone mineral density; T-cell activation; Immune senescence