Osteopenic Effect of Disulfiram Therapy in Patients With Alcohol Use Disorder

Disulfiram is widely used to treat alcohol use disorder. Alcohol per se adversely affects bone health. In the experimental study, disulfiram leads to apoptosis of osteoblast and significant osteopenia in adult rats. The present study explored the possibility of the occurrence of similar osteopenic effects of disulfiram therapy in patients with alcohol use disorder.

To assess the impact of disulfiram on bone health in patients with alcohol use disorder.

The study design was longitudinal observational. Subjects included 40 males with alcohol use disorder (aged 35.7±7.1 years, body mass index: 23.4±3.8 kg/m²) who were initiated on disulfiram therapy at our tertiary care addictive disorders treatment center. They were assessed for bone mineral density at the lumbar spine, total hip, femoral neck, and forearm, at baseline and again at three time points (i.e., three-, six-, and 12-month follow-up on disulfiram therapy). Since all the patients did not come at all the above three follow-up points, the follow-up on the maximum period of disulfiram therapy at any of these three time points was considered as the final follow-up. Serum total-calcium, phosphorus, albumin, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D (25(OH)D), and bone-turnover marker (i.e., osteocalcin and β-carboxy-terminal telopeptides (β-CTx)) were measured at baseline and final follow-up. Statistical analyses were performed using Student's t-test for normally distributed and the Mann-Whitney U test for non-normally distributed data. A two-tailed p-value <0.05 was considered significant.

The median (interquartile range) duration of alcohol use and alcohol use disorder were 15.0 (10.0-20.0) and 8.0 (5.0-12.0) years, respectively. Patients had taken disulfiram for a mean period of 225±109 days, with 65% therapeutic adherence. Serum transaminases improved significantly during follow-up, indicating abstinence from alcohol intake. Despite alcohol withdrawal, lumbar spine bone mineral density decreased significantly at the final follow-up (0.942±0.105 gm/cm² vs 0.924±0.108 gm/cm², p=0.003). A decrease in lumbar-spine bone mineral density > least significant change occurred in 41.7% of patients following 12 months of disulfiram use. A reduction in bone mineral density correlated with adherence to disulfiram therapy (r=0.233, p=0.15). The median serum β-CTx/osteocalcin ratio increased after disulfiram (12.5 (9.7-17.4) vs 16.3 (11.8-19.9), p=0.033).

This study highlights a significant reduction in lumbar-spine bone mineral density and an increase in the β-CTx/osteocalcin ratio in patients with alcohol use disorder undergoing disulfiram therapy. These findings suggest that, despite the benefits of alcohol cessation facilitated by disulfiram, there is a notable risk of osteopenia that warrants careful monitoring. Clinicians should consider regular bone health assessments and proactive measures to mitigate bone density loss in this patient population.