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      Prevalence of and risk factors for low bone mineral density in Spanish treated HIV-infected patients

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          Abstract

          Objectives

          Several studies have involved antiretroviral therapy in the pathogenesis of low bone mineral density (BMD), while others have not confirmed this association. In this study we analyze the impact of HIV status, traditional risk factors and antiretroviral therapy in BMD in an HIV-infected population living in Madrid.

          Material and methods

          We performed a cross-sectional analysis of 107 individuals infected with HIV and exposed to antiretroviral treatment to estimate the prevalence of decreased BMD. Bone mineral density of lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. In a multivariate analysis variables related with HIV status, antiretroviral drugs and traditional risk factors were included.

          Results

          Low BMD was diagnosed in 63 participants (58.9%), including osteoporosis in 11 (10%). At least one cause of osteoporosis was identified in 43 patients (40%), with a deficiency of vitamin D in 86 (89%) and secondary hyperparathyroidism in 30 (28%). In multivariate analysis, increasing age, a treatment based on boosted PI and tenofovir DF, and previous exposure to tenofovir were identified as independent risk factors for a decreased BMD in both lumbar spine and femoral neck.

          Conclusions

          We have confirmed a high prevalence of reduced BMD, which is favoured by ritonavir-boosted PI and TDF. Bone safety should continue to be evaluated in clinical trials and cohort studies in order to demonstrate that the new drugs offer additional advantages regarding the impact on BMD.

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          Most cited references18

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          Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.

          To determine the ability of measurements of bone density in women to predict later fractures. Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Eleven separate study populations with about 90,000 person years of observation time and over 2000 fractures. Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density.
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            Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy.

            The use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time. We performed a cross-sectional analysis of whole-body, lumbar spine (L1-L4) and proximal femur bone mineral density in 112 male subjects (HIV-infected patients on HAART that included a protease inhibitor, HIV-infected patients not receiving a protease inhibitor and healthy seronegative adults) using dual energy x-ray absorptiometry. Men receiving protease inhibitors had a higher incidence of osteopenia and osteoporosis according to World Health Organization definitions: relative risk = 2.19 (95% confidence interval 1.13-4.23) (P = 0.02). Subjects receiving protease inhibitors had greater central: appendicular adipose tissue ratios than the other two groups (P < 0.0001). There was no relationship between the central: appendicular fat ratio and the lumbar spine or proximal femur bone mineral density t- or z- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART. Osteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution.
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              High prevalence of and progression to low bone mineral density in HIV-infected patients: a longitudinal cohort study.

              Low bone mineral density (BMD) is an emerging metabolic condition in HIV-infected patients; however, data on progression of this disease are scarce. We studied 671 patients with at least one dual-energy X-ray absorptiometry scan (391 of them ≥2 scans) to determine the prevalence and progression of BMD and establish related factors. Linear regression and logistic polytomic regression were used for the cross-sectional study and mixed effects and generalized estimating equations were used for the longitudinal study. Osteopenia and osteoporosis were diagnosed in 47.5 and 23%, respectively. Progression to bone demineralization was observed in 28% of the patients over a median of 2.5 years (12.5% progressed to osteopenia and 15.6% to osteoporosis). In the 105 patients with at least 5 years of follow-up, progression was 47% (18% to osteopenia; 29% to osteoporosis). Factors associated with bone loss and progression were age [odds ratio (OR) 1.07; 95% confidence interval (CI) 1.05-1.08; P < 0.0001], male sex (OR 2.23; 95% CI 1.77-2.8; P < 0.0001), low body mass index (OR 1.14; 95% CI 1.11-1.17; P < 0.0001), time on protease inhibitor (OR 1.18; 95% CI 1.12-1.24; P < 0.0001), time on tenofovir (OR 1.08; 95% CI 1.03-1.14; P < 0.0019), and current use of protease inhibitors (OR 1.64; 95% CI 1.35-2.04; P < 0.0001). Our results show a high prevalence of and considerable progression to osteopenia/osteoporosis in our cohort. Our findings support the importance of applying adequate strategies to prevent bone demineralization and of close monitoring of BMD in HIV-infected patients, specifically in at-risk patients who are taking antiretrovirals that affect bone mineralization.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Visualization
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Visualization
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Visualization
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 April 2018
                2018
                : 13
                : 4
                : e0196201
                Affiliations
                [1 ] Department of Internal Medicine, Severo Ochoa University Hospital, Leganés, Madrid, Spain
                [2 ] Department of Endocrinology, Severo Ochoa University Hospital, Leganés, Madrid, Spain
                [3 ] Department of Biochemistry, Severo Ochoa University Hospital, Leganés, Madrid, Spain
                [4 ] Department of Infectious Diseases, Ramón y Cajal Hospital, University of Alcalá de Henares, IRYCIS, Madrid, Spain
                Imperial College London, UNITED KINGDOM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-9387-7917
                Article
                PONE-D-17-16002
                10.1371/journal.pone.0196201
                5927434
                29709013
                b6d4c67c-415f-4e67-9f41-14a296d4d801
                © 2018 Cervero et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 April 2017
                : 9 April 2018
                Page count
                Figures: 0, Tables: 15, Pages: 18
                Funding
                Funded by: Foundation Universidad Alfonso X el Sabio
                Award ID: IX CONVOCATORIA SANTANDER / UAX.
                Award Recipient :
                Foundation Universidad Alfonso X el Sabio has provided financial support for the project leading to this publication.
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
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                Infectious diseases
                Viral diseases
                HIV infections
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                Diagnostic medicine
                HIV diagnosis and management
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                Biochemistry
                Hormones
                Parathyroid Hormone
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                Microbial Pathogens
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                Immunodeficiency Viruses
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                All relevant data are within the paper and in the Dryad Data repository at the following DOI: 10.5061/dryad.f35f51g.

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