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.
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.
1. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis
: a meta-analytic review. AIDS. 2006;20:2165–2174.
2. Lawal A, Engelson E, Wang J, et al.. Equivalent osteopenia in HIV
-infected individuals studied before and during the era of highly active antiretroviral therapy. AIDS. 2001;15:278–280.
3. Knobel H, Guelar A, Valecillo G, et al.. Osteopenia in HIV
-infected patients: is it the disease or is it the treatment? AIDS. 2001;15:807–808.
4. Mondy K, Tebas P. Emerging bone problems in patients infected with human immunodeficiency virus. Clin Infect Dis. 2003;36:S101–S105.
5. Tebas P, Powderly WG, Claxton S, et al.. Accelerated bone mineral loss in HIV
-infected patients receiving potent antiretroviral therapy. AIDS. 2000;14:F63–F67.
6. Madeddu G, Spanu A, Solinas P, et al.. Bone mass loss and vitamin D metabolism impairment in HIV
patients receiving highly active antiretroviral therapy. Q J Nucl Med Mol Imaging. 2004;48:39–48.
7. Bruera D, Luna N, David DO, et al.. Decreased bone mineral density
-infected patients is independent of antiretroviral therapy. AIDS. 2003;17:1917–1923.
8. Dolan SE, Huang JS, Killilea KM, et al.. Reduced bone density in HIV
-infected women. AIDS. 2004;18:475–483.
9. Bedimo R, Maalouf NM, Zhang S, et al.. Osteoporotic fracture risk associated with cumulative exposure of tenofovir and other antiretroviral agents. AIDS. 2012;26:825–831.
10. Hansen ABE, Gerstoft J, Kronborg G, et al.. Incidence of low and high-energy fractures in persons with and without HIV
infection: a Danish population-based cohort study. AIDS. 2012;26:285–293.
11. Mundy LM, Youk AO, McComsey GA, et al.. Overall benefit of antiretroviral treatment on the risk of fracture in HIV
: nested case–control analysis in a health-insured population. AIDS. 2012;26:1073–1082.
12. Sambrook P, Cooper C. Osteoporosis
. Lancet. 2006;367:2010–2018.
13. Cazanave C, Dupon M, Lavignolle-Aurillac V, et al.. Reduced bone mineral density
-infected patients: prevalence and associated factors. AIDS. 2008;22:395–402.
14. Nakchbandi IA, Van der Merwe SW. Current understanding of osteoporosis
associated with liver disease. Gastroenterol Hepatol. 2009;6:660–670.
15. World Health Organization, eds. Prevention and Management of Osteoporosis
. Report of a WHO Scientific Group. Geneva, Switzerland: WHO; 2003.
16. Hay JE, Guichelaar MMJ. Evaluation and management of osteoporosis
in liver disease. Clin Liver Dis. 2005;9:747–766.
17. Leslie WD, Bernstein CN, Leboff MS. American Gastroenterology Association technical review on osteoporosis
in hepatic disorders. Gastroenterol. 2003;125:941–966.
18. George J, Ganesh HK, Acharya S, et al.. Bone mineral density
and disorders of mineral metabolism in chronic liver disease. World J Gastroenterol. 2009;15:3516–3522.
19. Collier J. Bone disorders in chronic liver disease. Hepatology. 2007;46:1271–1278.
20. Schiefke I, Fach A, Wiedmann M, et al.. Reduced bone mineral density
and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. World J Gastroenterol. 2005;11:1843–1847.
21. Gallego Rojo FJ, Gonzalez-Calvin JL, Muños-Torres M, et al.. Bone mineral density
, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis
. Hepatology. 1998;28:695–699.
22. Collin F, Duval X, Le Moing V, et al.. Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults. AIDS. 2009;23:1021–1026.
23. Young B, Dao CN, Buchacz K, et al.. Increased rates of bone fracture among HIV
-infected persons in the HIV
outpatient study (HOPS) compared with the US general population, 2000–2006. Clin Infect Dis. 2011;52:1061–1068.
24. Lo Re V III, Guaraldi G, Leonard MB, et al.. Viral hepatitis
is associated with reduced bone mineral density
-infected women but not men. AIDS. 2009;23:2191–2198.
25. Loko MA, Salmon D, Carrieri P, et al.. The French national prospective cohort of patients co-infected with HIV
and HCV (ANRS CO13 HEPAVIH): early findings, 2006–2010. BMC Infect Dis. 2010;10: 303–313.
26. Sandrin L, Fourquet B, Hasquenoph JM, et al.. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29:1705–1713.
27. Imbert-Bismut F, Ratziu V, Pieroni L, et al.. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069–1075.
28. Fausto A, Bongiovanni M, Cicconi P, et al.. Potential predictive factors of osteoporosis
-positive subjects. Bone. 2006;38:893–897.
29. Jacobson DL, Spiegelman D, Knox TK, et al.. Evolution and predictors of change in total bone mineral density
over time in HIV
-infected men and women in the Nutrition for Healthy Living Study. J Acquir Immune Defic Syndr. 2008;49:298–308.
30. Bolland MJ, Grey AB, Gamble GD, et al.. Low body weight mediates the relationship between HIV
infection and low bone mineral density
: a meta-analysis. J Clin Endocrinol Metab. 2007;92:4522–4528.
31. McComsey GA, Kitch D, Daar ES, et al.. Bone mineral density
and fractures in antiretroviral-naive persons randomized to receive abacavir–lamivudine or tenofovir disoproxil fumarate–emtricitabine along with efavirenz or atazanavir–ritonavir: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203:1791–1801.
32. Mehsen N, Lawson-Ayayi S, Schaeverbeke T, et al.. Cardiovascular risk and osteoporosis
are associated in HIV
-infected patients, ANRS CO3 Aquitaine Cohort, France [Abstract TUPE246]. Presented at: 6th International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention; July 17-20, 2011; Roma, Italy.
33. Kerschan-Schindl K, Wendlova J, Kudlacek S, et al.. Serum levels of receptor activator of nuclear factor kappaB ligand (RANKL) in healthy women and men. Exp Clin Endocrinol Diabetes. 2008;116:491–495.
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.