Methadone Maintenance Treatment, Sex Hormones, and Bone Mineral Density in Persons Who Inject Drugs.

Context: Methadone maintenance treatment (MMT) has been used to treat opioid use disorder, but is associated with bone loss. Sex hormones may mediate this relationship, though studies are limited. Objective: This work aimed to assess the relationships among bone mineral density (BMD) T-score, sex hormones, and MMT among individuals who inject drugs. Methods: We included study participants from the AIDS Linked to the Intravenous Experience (ALIVE) cohort. We performed multivariable linear regression to assess the association of MMT with BMD T-scores (lumbar spine, total hip, and femoral neck) in men and women. We further assessed whether sex hormones estradiol (E2) and free testosterone (free T) influenced the association between MMT and BMD in men and women. We controlled for age, sex, body mass index, smoking and heavy alcohol use (≥3 times per week), HIV status and/or hepatitis C virus viremia, vitamin D level, and heroin use. Results: Among 245 participants (153 men; 92 women), 107 were receiving MMT. Men undergoing MMT were more likely to have a low free T level compared to men not receiving MMT (odds ratio, 3.99; 95% CI, 1.40-11.39; P = .010). No significant differences in the odds of menopause in women by MMT status were observed. Individuals on MMT had significantly lower lumbar spine T-scores (β: -.55; 95% CI, -1.06 to -.05), independent of covariates. After adjusting for E2 and/or free T, the association between MMT and BMD was not significant, suggesting potential mediation. Conclusion: Among men who inject drugs, MMT may contribute to decreased BMD, potentially through decreased levels of free T and total E2.