ORIGINAL PAPER Molecular Bases of Osteoporosis in HIV: The Role of the Virus and Antiretroviral Therapy D. Gibellini • M. Borderi • E. Vanino • A. Clo ` • S. Morini • L. Calza • M. C. Re • Pl. Viale Published online: 25 April 2012 Ó Springer Science+Business Media, LLC 2012 Abstract In addition to immune system, HIV infection can determine the onset of functional dysfunctions of several organs and tissues such as central nervous system, cardiovascular system, kidney, and bone. It is noteworthy that HIV-infected individuals show an increased risk of bone mass loss with subsequent osteopenia and osteopo- rosis development. Interestingly, antiretroviral therapy is not able to tackle the bone derangement but, on the con- trary, it can induce a progressive bone mass loss, especially when specific antiretroviral drugs are used. In this report, we summarized the HIV and antiretroviral-related mecha- nisms involved in the osteopenia and osteoporosis induction. Keywords HIV Á Bone Á Osteopenia/osteoporosis Á Virus Á Antiretrovirals Introduction The antiretroviral therapy (ART) advent has determined a dramatic change in the therapy and management of HIV disease. This treatment has transformed a lethal disease into a chronic disease, and it is now common to consider the life expectancy of these patients over 35 years from the time of diagnosis [1]. This improvement has determined that, in addition to immune system and viral load moni- toring, the physicians must also focus their efforts on the management and treatment of progressive lesions in central nervous system, kidney, heart, and bone [2]. In particular, HIV-infected individuals show several bone lesions that are especially correlated with the development of osteopenia and osteoporosis [3] and with a higher risk of fractures, which represents a negative index for life expectancy [4]. In this review, we will discuss the principal studies per- formed on viral and/or antiretroviral-related mechanisms that have been related to osteopenia and osteoporosis in HIV-positive individuals. Bone Structure, Osteopenia, and Osteoporosis The bone is a dynamic tissue formed by a continuous process of bone modeling and resorption, which involves the osteoblasts and osteoclasts [5]. The osteoblasts regulate the bone building phase through the production and deposition of bone matrix and its mineralization. The osteoclasts, on the contrary, regulate the bone resorption. Once formed, the adult bone is continuously remodeled throughout life to assure its homeostasis [6]. The bone remodeling cycle is mainly activated by microcracks and loss of mechanical loading of bone structure and consists in specific different stages where the early phases are char- acterized by a rapid activation of osteoclast-dependent bone resorption followed by osteoblast-mediated bone rebuilding [5]. It is noteworthy that the osteoblastic bone formation, which lasts about 3 months in humans, is a much slower process than osteoclastic bone resorption. The modulation of bone is also regulated by several factors such as hormones, vitamins, and cytokines [7] that modu- late the osteoblast/osteoclast cross-talk, adding complexity D. Gibellini Á A. Clo ` Á S. Morini Á M. C. Re Department of Haematology and Oncological Sciences, Microbiology Section, University of Bologna, Bologna, Italy M. Borderi (&) Á E. Vanino Á L. Calza Á Pl. Viale Department of Internal Medicine, Aging and Nephrology, Infectious Diseases Section, University of Bologna, Bologna, Italy e-mail: marco.borderi@aosp.bo.it 123 Clinic Rev Bone Miner Metab (2012) 10:236–245 DOI 10.1007/s12018-012-9133-y