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

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.

Third-Generation Antipsychotics and Lurasidone in the Treatment of Substance-Induced Psychoses: A Narrative Review

“…This high D 3 affinity is significant, considering that most antipsychotics have a lower affinity for this receptor, leading to inadequate D 3 receptor occupancy in the brain. This unique affinity is crucial for cariprazine's clinical efficacy, as indicated by PET studies on schizophrenic patients, demonstrating a stronger effect on the D 3 receptor compared to the D 2 receptor [41][42][43][44][45][46][47] (see Table S6).…”

Bone Health in Mood Disorders: A Narrative Review about Clinical and Biological Connections

“…This may happen through dopamine, serotonin, and adrenergic receptor signaling since these receptors were found on osteoclasts and osteoblasts [115]. The recent review conducted by Weerasinghe and colleagues provided an overview of first-, second-, and third-generation antipsychotics' effects on bone formation and resorption, influencing the expression profiles of dopamine, serotonin, and adrenergic receptors through intracellular pathways [116]. The study by Raffin and colleagues highlighted that, when exposed to iatrogenic hyperprolactinemia caused by second-generation APs, young psychiatric patients may face a cumulative risk of osteoporosis, suggesting that the secretion and activity of prolactin, as well as its balance with vitamin D, are also involved in the complex interplay of factors connecting mood disorders and bone health and may become clinical indicators [117].…”

Biofabrication of functional bone tissue: defining tissue-engineered scaffolds from nature

“…The bone mass can be affected by a variety of conditions, including osteogenesis imperfecta, hyperprolactinaemia, hyperparathyroidism, rheumatoid arthritis, liver disease, myeloma, osteosarcoma, as well as the use of medications such as glucocorticoids, immunosuppressant, chemotherapy, anticoagulants, and antipsychotics ( Oderda et al, 2012 ; Kenkre and Bassett, 2018 ; Azimi Manavi et al, 2023 ; Weerasinghe et al, 2023 ). Diseases such as osteoarthritis and osteosarcoma are leading causes of disability and have a major effect on the socioeconomic burden globally.…”