Methadone Maintenance Treatment, Sex Hormones and Low Bone Density in a Population of Injection Drug Users

Background: Methadone maintenance treatment (MMT) is associated with low bone mineral density (BMD) in those treated for opioid addiction. However, it is unclear whether observed adverse effects on the skeleton are related to a direct effect of opioids on bone metabolism or mediated by other mechanisms including MMT-induced gonadal dysfunction. We hypothesized that MMT is associated with low BMD in persons with a history of injection drug use (PWID) and that this effect is explained by differences in sex hormones. Methods: We recruited 280 participants from the AIDS Linked to the Intravenous Experience (ALIVE) study, a long-standing cohort of PWID. All participants had been exposed to hepatitis C virus (HCV antibody positive). In addition to a morning assessment of free testosterone (FT) and estradiol (E2), all participants underwent dual-energy x-ray absorptiometry (DXA) of the lumbar spine (LS) and hip (total hip (TH) and femoral neck (FN)). Multivariable linear regression was used to assess the relationship between MMT and T-score with and without inclusion of E2/FT concentrations. Models were stratified by sex and adjusted for age, BMI, HCV infection, HIV, current alcohol use, current smoking, vitamin D3 level, and current heroin use. Results: All participants were African American and 37% female. The median (Q1, Q3) age was 57 years (51, 61), median (Q1, Q3) BMI was 26 kg/m(2) (22, 30) and 107 (38%) were receiving MMT. FT and E2 were significantly lower in men receiving MMT vs not (p < 0.01 for both). In women, there were no differences in sex hormones based on MMT use. The prevalence of low BMD (defined as LS, TH, or FN T-score ≤ -1) was 25% (23% in men and 29% in women; p = 0.3); 12 (4.3%, 2 men and 8 women; p = 0.09) had osteoporosis (T-score ≤ -2.5). In men, MMT was associated with -0.7 lower LS-T score (95% CI [-1.3, -0.1], p=0.046) in adjusted models compared to those not receiving MMT. The magnitude of this association was reduced after adjusting for E2 and FT (-0.2, 95% CI [-0.8, 0.5], p=0.665)). In women, MMT was not associated with LS-T score (MD -0.3, 95% CI [-1.3, 0.4], p=0.631). There were no associations between MMT and TH or FN BMD in either men or women. Conclusion: In this study, MMT was associated with lower lumbar spine BMD in men with a history of IDU, which was potentially mediated by the effect of MMT on sex hormones. More rigorous screening for co-morbidities including hypogonadism and low BMD in men receiving MMT may be warranted.