Vol.:(0123456789) 1 3 Journal of Bone and Mineral Metabolism https://doi.org/10.1007/s00774-018-0908-1 ORIGINAL ARTICLE Efect of escitalopram and carbidopa on bone markers in Wistar rats: a preliminary experimental study Ravisha Wadhwa 1  · Manoj Kumar 2  · Yam Nath Paudel 1  · Ramsha Iqbal 2  · Priyanka Kothari 3  · Ritu Trivedi 3  · Divya Vohora 1,2 Received: 8 March 2017 / Accepted: 16 January 2018 © The Japanese Society for Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2018 Abstract In view of the opposite efects of gut and brain serotonin in bone, the key role of Wnt β/catenin pathway in osteoblastic proliferation and the controversial bony efects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the efects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on mark- ers of bone turnover and Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0 mg/kg, p.o.) and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days following which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline phosphatase) bone formation and bone resorption markers (receptor activator of nuclear factor κB ligand, tartrate-resistant acid phosphatase 5b) were determined. Our results indicated that escitalopram adversely afected bone as indicated by reduced bone formation and enhanced bone resorption. Further, the efects of escitalopram on bone formation were possibly mediated through gut serotonin while the mechanisms responsible for efects on resorption seem unrelated to gut serotonin. The promising efects of carbidopa on bone formation, as observed in our study, open up exciting possibilities for this drug requiring further investigations. Keywords Escitalopram · Carbidopa · Alkaline phosphatase · RANKL · Sclerostin Introduction Though adverse efects of selective serotonin reuptake inhib- itors (SSRIs) on bone health have been studied since 1990, however, results were found to be controversial [1, 2]. While studies demonstrated enhanced bone resorption following SSRIs, they also provided evidence for increased bone formation [3]. It was reported recently that centrally and peripherally synthesized serotonin may have opposite efects on bone formation [4]. Despite this, whether the actions of SSRIs on bone are mediated through brain or periphery is not yet established. Peripheral decarboxylase inhibitor (car- bidopa) can inhibit synthesis of serotonin peripherally and thus can be used to study the role of central 5HT modula- tion by SSRIs on bone. Moreover, carbidopa was recently hypothesized to have protective efects on bone [5], indicat- ing the role of central serotonin in bone formation. Esci- talopram is a relatively newer SSRI and is S-enantiomer of the racemic citalopram. The drug is comparatively safe and efective in the treatment of depression. However, the preclinical data regarding its efects on bone are still not established. Recently, activation of the Wnt/β-catenin pathway has been demonstrated to play a key role in controlling prolif- eration, osteoblast diferentiation and, thus, bone formation [6]. Low-density lipoprotein receptor-related protein (LRP5) which acts as a co-receptor in the Wnt/β-catenin pathway is an inhibitor of the enzyme tyrosine hydroxylase (tph), which is the rate-limiting enzyme for serotonin synthesis. Thus, LRP5 inhibits the serotonin synthesis. Dickkopf-1 (DKK- 1) and sclerostin (SOST) are two inhibitors of Wnt pathway and can act as biomarkers for reduced bone formation [7, 8]. * Divya Vohora dvohra@jamiahamdard.ac.in; divyavohora@hotmail.com 1 Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India 2 Pharmaceutical Medicine, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India 3 Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India