Effect of escitalopram and carbidopa on bone markers in Wistar rats: a preliminary experimental study
In view of the opposite effects of gut and brain serotonin in bone, the key role of Wnt β/catenin pathway in osteoblastic proliferation and the controversial bony effects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the effects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on markers 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 affected bone as indicated by reduced bone formation and enhanced bone resorption. Further, the effects of escitalopram on bone formation were possibly mediated through gut serotonin while the mechanisms responsible for effects on resorption seem unrelated to gut serotonin. The promising effects of carbidopa on bone formation, as observed in our study, open up exciting possibilities for this drug requiring further investigations.
KeywordsEscitalopram Carbidopa Alkaline phosphatase RANKL Sclerostin
This work was carried out in UGC-SAP assisted Neurobehavioral Pharmacology Laboratory. We thank M. Raj for helping in arranging carbidopa sample from Shodhana Laboratories, Hyderabad. Special thanks to Dr. Bibhu Prasad Panda, for permission to work in Pharmaceutical Biotechnology Laboratory (Jamia Hamdard). The work was supported by fellowship from AICTE (GPAT).
Compliance with ethical standards
Conflict of interest
The authors report no conflicts of interest.
- 5.Radaei F, Gharibzadeh S (2013) The effect of carbidopa in carbidopa-levodopa combination on reducing osteoporotic symptoms in Parkinson’s disease patients. Brain Disord Ther 2:2Google Scholar
- 12.Kaiser M, Mieth M, Liebisch P, Oberländer R, Rademacher J, Jakob C, Kleeberg L, Fleissner C, Braendle E, Peters M, Stover D, Sezer O, Heider U (2008) Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol 80:490–494CrossRefGoogle Scholar
- 13.Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiore CE (2010) Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95:2248–2253CrossRefGoogle Scholar
- 14.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin Phenol reagent. J Biol Chem 193:265–275Google Scholar
- 15.Ominsky MS, Li X, Asuncion FJ, Barrero M, Warmington KS, Dwyer D, Stolina M, Geng Z, Grisanti M, Tan HL, Corbin T, McCabe J, Simonet WS, Ke HZ, Kostenuik PJ (2008) RANKL inhibition with osteoprotegerin increases bone strength by improving cortical and trabecular bone architecture in ovariectomized rats. J Bone Miner Res 23:672–682CrossRefGoogle Scholar
- 18.Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138:976–989CrossRefGoogle Scholar
- 20.Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML (2013) The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone 56:42–47CrossRefGoogle Scholar
- 21.Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P (2010) Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med 16:308–312CrossRefGoogle Scholar