Zoledronate treatment duration is linked to bisphosphonate‐related osteonecrosis of the jaw prevalence in rice rats with generalized periodontitis

ObjectivesTo determine the extent that zoledronate (ZOL) dose and duration is associated with bisphosphonate‐related osteonecrosis of the jaw (BRONJ) prevalence in rice rats with generalized periodontitis (PD), characterize structural and tissue‐level features of BRONJ‐like lesions in this model, and examine the specific anti‐resorptive role of ZOL in BRONJ.Materials and MethodsRice rats (n = 228) consumed high sucrose‐casein diet to enhance generalized PD. Groups of rats received 0, 8, 20, 50 or 125 µg/kg IV ZOL/4 weeks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n = 9–16) were necropsied after 12, 18, 24 and 30 weeks of treatment. BRONJ‐like lesion prevalence and tissue‐level features were assessed grossly, histopathologically and by MicroCT. ZOL bone turnover effects were assessed by femoral peripheral quantitative computed tomography, serum bone turnover marker ELISAs and osteoclast immunolabelling.ResultsPrevalence of BRONJ‐like lesions was significantly associated with (a) ZOL treatment duration, but plateaued at the lowest oncologic dose, and (b) there was a similar dose‐related plateau in the systemic anti‐resorptive effect of ZOL. ZOL and BRONJ‐like lesions also altered the structural and tissue‐level features of the jaw.ConclusionThe relationship between BRONJ‐like lesion prevalence and ZOL dose and duration varies depending on the co‐ or pre‐existing oral risk factor. At clinically relevant doses of ZOL, BRONJ‐like lesions are associated with anti‐resorptive activity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149302/1/odi13052.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149302/2/odi13052_am.pd

Schizophrenia: a disorder of broken brain bioenergetics

A substantial and diverse body of literature suggests that the pathophysiology of schizophrenia is related to deficits of bioenergetic function. While antipsychotics are an effective therapy for the management of positive psychotic symptoms, they are not efficacious for the complete schizophrenia symptom profile, such as the negative and cognitive symptoms. In this review, we discuss the relationship between dysfunction of various metabolic pathways across different brain regions in relation to schizophrenia. We contend that several bioenergetic subprocesses are affected across the brain and such deficits are a core feature of the illness. We provide an overview of central perturbations of insulin signaling, glycolysis, pentose-phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation in schizophrenia. Importantly, we discuss pharmacologic and nonpharmacologic interventions that target these pathways and how such interventions may be exploited to improve the symptoms of schizophrenia