Antipsychotic-induced bone loss: the role of dopamine, serotonin and adrenergic receptor signalling

D Kavindi Weerasinghe; Jason M Hodge; Julie A Pasco; Rasika M Samarasinghe; Behnaz Azimi Manavi; Lana J Williams

doi:10.3389/fcell.2023.1184550

Antipsychotic-induced bone loss: the role of dopamine, serotonin and adrenergic receptor signalling

Front Cell Dev Biol. 2023 May 25:11:1184550. doi: 10.3389/fcell.2023.1184550. eCollection 2023.

Authors

D Kavindi Weerasinghe¹, Jason M Hodge^{1

2}, Julie A Pasco^{1

2

3}, Rasika M Samarasinghe¹, Behnaz Azimi Manavi¹, Lana J Williams^{1

2}

Affiliations

¹ IMPACT-The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia.
² Barwon Health, Geelong, VIC, Australia.
³ Department of Medicine-Western Health, The University of Melbourne, Melbourne, VIC, Australia.

Abstract

Antipsychotics are commonly used in treating psychiatric disorders. These medications primarily target dopamine the serotonin receptors, they have some affinity to adrenergic, histamine, glutamate and muscarinic receptors. There is clinical evidence that antipsychotic use decreases BMD and increases fracture risk, with dopamine, serotonin and adrenergic receptor-signalling becoming an increasing area of focus where the presence of these receptors in osteoclasts and osteoblasts have been demonstrated. Osteoclasts and osteoblasts are the most important cells in the bone remodelling and the bone regeneration process where the activity of these cells determine the bone resorption and formation process in order to maintain healthy bone. However, an imbalance in osteoclast and osteoblast activity can lead to decreased BMD and increased fracture risk, which is also believed to be exacerbated by antipsychotics use. Therefore, the aim of this review is to provide an overview of the mechanisms of action of first, second and third generation antipsychotics and the expression profiles of dopamine, serotonin and adrenergic receptors during osteoclastogenesis and osteoblastogenesis.

Keywords: antipsychotics; bone mineral density; dopamine; noradrenaline; osteoblast; osteoclast; schizophrenia; serotonin.

Publication types

Review

Grants and funding

This work was supported by the National Health and Medical Research Council (NHMRC), Australia (Grant Nos 1162867). DKW and BAM were supported by the Deakin University Postgraduate Research Scholarship (DUPRS) and LW by the NHMRC Emerging Leadership Fellowship (Grant No. 1174060).