Effects of Escitalopram on Markers of Bone Turnover: A Randomized Clinical Trial

Context: Recent observational studies have suggested that the use of selective serotonin reuptake inhibitors is associated with an increased fracture risk and an accelerated bone loss, although conflicting results have been reported. Furthermore, because many of these studies have been performed in depressed women, confounding by indication may influence these findings. Objective: The objective of the study was to determine whether selective serotonin reuptake inhibitors affect bone metabolism Design: This was a randomized controlled trial. Setting: The study was conducted in four US clinical sites. Participants: Healthy peri-and postmenopausal women participated in the study. Intervention: The intervention was escitalopram (10-20 mg/d) for the treatment of vasomotor symptoms. Main Outcome Measures: Serum carboxyterminal collagen crosslinks (CTX) and serum amino-terminal propeptide of type I collagen (P1NP) were measured. Results: One hundred forty-one peri-or postmenopausal nondepressed women (mean age 53.7 y, SD 4.1) had baseline and 8-week follow-up samples available for analysis and were included in the study (69 escitalopram, 72 placebo). The groups were balanced across a broad range of baseline characteristics, including age, race, body mass index, smoking status, and mood symptoms. The between-group differences in the change in CTX and P1NP from baseline to week 8 were compared by a repeated-measures linear regression model adjusted for race, clinical center, and baseline measurement. Treatment with escitalopram reduced serum P1NP by 1.02 ng/mL on average [95% confidence interval (CI) -5.17, 3.12] compared with a reduction of 1.88 ng/mL (95% CI -4.82, 1.06) in the placebo group (P = .65). Similarly, serum CTX decreased 0.02 ng/mL on average (95% CI -0.05, 0.01) in the escitalopram group compared with 0.00 ng/mL(95% CI -0.02,0.02) in the placebo group(P = .24). The results were similar when the analysis was restricted to those women whose adherence to study medication was 70% or greater. Conclusions: Although the study was limited to 8 weeks, these results suggest that escitalopram does not significantly alter bone metabolism in the short term.