Elucidating the Mechanism(s) Underlying Antipsychotic- and Antidepressant-Mediated Fractures

Abstract

Mood spectrum disorders and medications used to treat these disorders, such as atypical antipsychotic drugs (AA), are associated with metabolic and endocrine side effects including obesity, dyslipidemia, hyperglycemia and increased risk of fractures. Antidepressant medications, including selective serotonin reuptake inhibitors (SSRI), have also been reported to increase fracture risk in some patients. The pharmacology underlying the increased risk of fractures is currently unknown. Possible mechanisms include alternations in dopaminergic and/or serotonergic signaling pathways. As these medications distribute to the bone marrow as well as to the brain, it is possible that drug-induced fractures are due to both centrally mediated effects as well as direct effects on bone turnover. Given the growing patient population that is prescribed these medications for both on- and off-label indications, understanding the level of risk and the mechanisms underlying drug-induced fractures is important for informing both prescribing and patient monitoring practices.

Antipsychotic therapies and bone health

“…Moreover, they are often used in children and older people. Antipsychotic therapies have been associated with increased risk of obesity, dyslipidemia and type 2 diabetes mellitus, while there is emerging clinical evidence that these medications can increase the risk of osteoporosis and fractures [1,2].…”

“…Many patients receiving antipsychotics have risk factors for osteoporosis, such as smoking, very low or very high body mass index (BMI), poor nutrition, low levels of physical activity, high levels of alcohol consumption, or vitamin D deficiency [3]. Furthermore, genetic predisposition, low-grade inflammation and elevated cytokines concentrations in patients with schizophrenia may additionally affect bone strength and quality [2].…”

“…Possible pathophysiological mechanisms of bone health problems after antipsychotic use include alterations in dopaminergic and/or serotonergic signaling pathways. As these medications are distributed to the bone marrow as well as to the brain, it is possible that drug-induced fractures are due to both centrally mediated effects and direct effects on bone turnover [2]. A popular hypothesis is that antipsychotics affect BMD and increase fracture risk due to hyperprolactinemia.…”

“…A popular hypothesis is that antipsychotics affect BMD and increase fracture risk due to hyperprolactinemia. Indeed, antipsychotic medications have caused hyperprolactinemia in women, men and children [2,9]. It is well known that the subsequent hypogonadism leads to bone loss.…”

“…Furthermore, dopamine is present in bone marrow, inhibiting osteoclastogenesis and osteoblastogenesis. The effects of dopamine antagonists in such molecular procedures may be responsible for the increased risk of osteoporosis in patients receiving these medications [2,13].…”