aSection of Infectious Diseases, Department of Internal Medicine, Geriatric Medicine and Nephrology, University of Bologna, Bologna, ItalybDepartment of Haematology and Oncologic Sciences, Section of Microbiology, ItalycCenter for Metabolic Bone Diseases, Gorizia Hospital, Gorizia, ItalydInteruniversity Consortium, National Institute Biostructure and Biosystem (INBB), Rome, Italy.
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IntroductionHIV mainly replicates in CD4+ T lymphocytes and monocyte/macrophages causing severe immunological impairment. In addition to the immune system, HIV infection affects tissues and organs such as kidney, liver, the central nervous system, heart and bone showing a complex pathogenesis .The advent and widespread use of highly active antiretroviral therapy (HAART) in the last two decades has led to a marked improvement in the treatment of HIV disease even though viral infection cannot be eradicated because HAART does not completely eliminate the viral reservoirs . HAART has dramatically changed the course of HIV infection from a fatal infection to a chronic and relatively manageable disease. The increased life expectancy of HIV patients and the effects of HAART have changed the management of HIV infection. Nowadays medical treatment is no longer focused solely on HIV infection, opportunistic diseases and monitoring immune derangement, but also includes the control of metabolic, cardiovascular, liver, bone and kidney complications. In particular, bone alterations have been observed in the course of HIV disease representing a pivotal clinical problem in the management of HIV patients especially for a possible development of bone fractures . The major bone lesions detectable in HIV patients are related to bone demineralization (osteopenia/osteoporosis and osteomalacia) and osteonecrosis ( for a review).This report will discuss the pathogenesis, diagnosis and treatment of major bone complications represented by bone demineralization diseases during HIV infection and HAART treatment.Osteopenia/osteoporosis in HIV-infected patientsBone alterations have been observed in the course of HIV disease since for nearly two decades (Table 1). In particular, reduced bone mineral density (BMD) is the most common bone lesion found in HIV-infected individuals [5,6]. BMD is a parameter that predicts fracture risk, which in turn correlates with a shorter life expectancy . BMD is measured by the dual X-ray absorptiometry scan (DXA). According to the WHO Classification, BMD is commonly reported in terms of DXA T-score, which represents the number of standard deviations below the mean of a young, sex-matched control population. T-score values are considered normal above the limit of −1. Values between −1 and −2.5 indicate osteopenia (low bone mass) whereas a T-score value below −2.5 signifies osteoporosis [8,9]. Osteoporosis is a systemic condition characterized by both quantitative and qualitative alterations that reduce bone strength .Several groups have used DXA to study BMD status during HIV infection. A meta-analysis of selected reports on bone loss in the whole HIV patient population (HAART treated plus naive) from 1994 to 2005 showed that these individuals had 6.4 fold increased odds of osteopenia and 3.7-fold increased odds of osteoporosis in comparison with uninfected individuals . The relation between antiretroviral treatment and osteopenia/osteoporosis has been noted in several studies [12–18] although other reports failed to find any influence of HAART on bone loss, disclosing no major differences between naive and HAART treated patients [19–23]. A recent study on 492 patients belonging to the Aquitaine Cohort reported osteopenia in 50% and osteoporosis in 30% of HIV-positive cases but multivariate analysis did not show a significant correlation to bone loss and cumulative HAART or specific drug class .In spite of these opposing findings, a meta-analysis of selected cross-sectional studies demonstrated that the odds of osteoporosis were increased 2.4 times in HAART-treated patients compared with naïve individuals . In addition, the meta-analysis by Brown and Qaqish on 12 studies disclosed that patients treated with protease inhibitors have a higher prevalence of reduced BMD and the odds of osteoporosis in protease inhibitor-treated patients are 1.