We documented high prevalence rates of osteoporosis, considering the average age of the HIV-infected patients recruited, but these are comparable with prevalence findings previously reported in our cohort 13 and by others.28 The frequency of osteoporosis was higher in HIV-infected patients with chronic viral hepatitis than among HIV monoinfected ones but did not differ according to cirrhotic status.
Older age and low BMI were associated with osteoporosis in both women and men. Low BMI is the only known modifiable risk factor of low BMD documented in this study as shown in a previous meta-analysis29; bone mass loss was also higher in men who have sex with men than in any other patients as previously reported.13
Most patients were clinically asymptomatic at the time of their DXA measurements and no marker of HIV disease progression was associated with osteopenia or osteoporosis in the multivariable model. Furthermore, neither infection duration nor advanced immunosuppression (CD4 count <200/μL) was associated with osteoporosis. Unlike some other reports,1,30 ART use was not found to be associated with reduced BMD in our analysis. We specifically investigated the nucleosidic and nucleotidic ART class, including lamivudine and tenofovir, as these specific drugs are known to be effective against HBV; but we could not identify any link.
The hypothesis of an epidemiological association between viral hepatitis and osteoporosis was the central aim of our study and was only confirmed in our HIV-infected female patients. Our results corroborate other findings published by Lo Re III et al24 who hypothesized that this association resulted from gender differences in the serum levels of hepatitis-associated cytokines, markers of bone resorption, or other factors that maintain bone balance [such as insulin-like growth factor-1 and osteoprotegerin (OPG)]. In healthy subjects, the increase in the serum receptor activator of nuclear factor kappa B ligand/OPG ratio leading to BMD loss was shown related to age, with gender differences.31 We previously identified in this cohort an association between decreased BMD and cardiovascular risk, which also supports common physiopathological mechanisms involving inflammatory factors.32 Our study was not designed to evaluate OPG and receptor activator of nuclear factor kappa B ligand levels.
Furthermore, our results do not match with published reports indicating an association between bone mass or mineral losses and liver fibrosis.33 Cirrhosis in HIV-infected patients with chronic viral hepatitis was not associated with BMD alteration in our series. The grading of cirrhosis severity we used did not detect a critical point of decline in liver disease progression as suggested in non HIV-infected populations.18,20,33
Our study had some limitations. The selection of coinfected patients occurred over 2 recruitment periods but was systematic in each period. Although we believed selection bias may exist, introduced by differences with the original coinfected patients, the cross-sectional study design did not allow a full causal assessment, but only independent association. Moreover, some potential confounders such as smoking, alcohol use, methadone use had not been collected at the time of the analysis, and the full multivariable model did not adjust on these variables.
Finally, the absence of markers of bone metabolism (such variables are not routinely measured) did not allow us to conclude about the underlying mechanisms of association between chronic viral hepatitis and osteoporosis in women.
In conclusion, our study strongly suggests that chronic viral hepatitis is associated with osteoporosis in HIV-infected women, but concludes that cirrhosis is not a condition significantly associated with osteoporosis in both genders. However, the contributive effects of cirrhosis and its consequences were not evaluated. Our findings have direct implications for clinical and therapeutical care of HIV-infected patients. For osteopenic or osteoporotic coinfected patients, preventive programs to reduce the BMD decline and the risk of fracture may be considered, while considering the specific needs of women, and should take into account the well-known risk factors (low BMI and older age). Attending physicians should encourage prevention and early treatment of bone loss to reduce fracture rate and ultimately improve patients' qualify of life.
Further longitudinal studies, are needed to elucidate the relationship between osteoporosis and chronic viral hepatitis, including inflammatory process accelerating bone mass loss.
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The Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA) coordinating the Aquitaine Cohort is organized as follows: Scientific committee: Prs F. Dabis (Principal Investigator), M. Dupon, P. Mercié, P. Morlat, JL. Pellegrin, and JM. Ragnaud. Epidemiology, Biostatistics: M. Bruyand, G. Chêne, F. Dabis, S. Lawson-Ayayi, R. Thiébaut. Infectious diseases, Internal Medicine: F. Bonnal, F. Bonnet, N. Bernard, O. Caubet, L. Caunègre, C. Cazanave, J. Ceccaldi, D. Chambon, I. Chossat, FA. Dauchy, C. De La Taille, S. De Witte, M. Dupon, A. Dupont, P. Duffau, H. Dutronc, S. Farbos, V. Gaborieau, MC. Gemain, Y. Gerard, C. Greib, M. Hessamfar, D. Lacoste, S. Lafarie-Castet, P. Lataste, E. Lazaro, D. Malvy, P. Mercié, E. Monlun, P. Morlat, D. Neau, A. Ochoa, JL. Pellegrin, JM. Ragnaud, MC. Receveur, S. Tchamgoué, MA. Vandenhende, JF. Viallard. Immunology: JF. Moreau, I. Pellegrin. Virology: H. Fleury, ME. Lafon, B. Masquelier, P. Trimoulet. Pharmacology: D. Breilh. Pharmacovigilance: G. Miremont-Salamé. Data collection: MJ. Blaizeau, M. Decoin, C. D’Ivernois, S. Delveaux, C. Hannapier, O. Leleux, B. Uwamaliya-Nziyumvira. Data management and Statistical analysis: S. Geffard, A. Kpozehouen, G. Palmer, D. Touchard.