Antipsychotics are a class of psychotropic medication used to treat psychosis. Among different side effects associated with antipsychotic use, lower bone density and increased fracture risk are being recognised as a major health problem. However, their mechanism of action on human osteoclasts and osteoblasts differentiation remains unclear.
Expression of dopamine, serotonin and adrenergic receptors were assessed in human osteoclast (precursors and mature) and osteoblast (non-mineralising and mineralising) using real time qPCR. Osteoclast formation and resorption were measured in the presence of first-(haloperidol), second-(olanzapine) and third-(aripiprazole) generation antipsychotics. Osteoblasts cultured with antipsychotics were assessed for alkaline phosphatase (ALP) and bone mineralisation. Cell viability and apoptosis were determined using Annexin-V flow cytometry.
Osteoclasts expressed 5HT2B and ADRB2 and osteoblasts expressed DRD2, 5HT2B and ADRB2, respectively. All antipsychotics inhibited osteoclast formation and resorption in the following order of potency: haloperidol>aripiprazole>olanzapine. Antipsychotics did not affect ALP activity, while haloperidol and aripiprazole, but not olanzapine, inhibited bone mineralisation. Antipsychotic-induced negative effects on bone remodeling cycle was not associated with apoptosis or alterations in dopamine, serotonin or adrenergic receptor expression.
Haloperidol and aripiprazole-induced net bone loss may occur as a result of a low bone turnover state. In contrast, although olanzapine decreased osteoclast formation and function, it did not affect osteoblast mineralisation; thus identifying olanzapine as a preferred option compared to haloperidol or aripiprazole regarding off-target effects on bone. This new information, in combination with the epidemiological findings to date, will aid in clinical decision making regarding antipsychotic prescriptions to optimise health outcome during long-term care.