Perspectives of personalized approach to prevention and treatment of anticonvulsant-induced osteoporosis via action on vitamin D exchange and VDR expression

Abstract

Anticonvulsant-induced osteoporosis (AIO) and associated pain syndromes and patient disabilities are an important interdisciplinary medical problem generated by various molecular, genetic and pathophysiological mechanisms. AIO are the most important pathological processes associated with chronic pain in adults with epilepsy. Standard approaches to their prevention and treatment do not always solve the problem of the progression of the pathological process and chronicity of AIO. This is the reason for the search for new personalized strategies for the prevention and treatment of AIO. Vitamin D metabolism, expression and specificity of vitamin D receptors (VDRs) may play a key role in the development of AIO and chronic back pain in patients with epilepsy. The aim of the study was to review publications on changes in the vitamin D system in patients with AIO. We searched for articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar. The search was carried out by key-words and their combinations. The role of vitamin D and VDR in the development of AIO and the chronicity of back pain has been demonstrated mainly in animal models and humans. Associative genetic studies have shown that single nucleotide variants (SNVs) of the VDR gene encoding VDR may be associated with the development of osteoporosis of the spine (including those associated with the intake of an anticonvulsants). The prospects for the use of vitamin D preparations for modulating the effect of anticonvulsants used to treat epilepsy are discussed. Genetic association studies of VDR gene SNVs are important for understanding the genetic predictors of AIO and chronic back pain in patients with epilepsy, as well as for developing new personalized pharmacotherapy strategies.

Pathophysiological Mechanisms of Antipsychotic-Induced Parkinsonism

“…The vitamin D3 receptor (VDR) is a widespread steroid receptor, mainly localized in the pigmented nigrostriatal tract and motor cortex [ 87 , 88 ], providing melanin synthesis, cytoskeletal stability, and calcium in the motor area [ 89 ]. Indirectly, the control of calcium during the inhibition of NMDA receptors (NMDAR) in the elimination of excitotoxicity in vitro and in vivo has been described [ 90 , 91 ]. In addition, NMDAR enhancement is involved in glutamate excitotoxicity, degeneration in the nigrostriatal tract and motor cortex by increasing inward calcium flow, thereby increasing the level of calcium in the brain [ 92 ].…”

“…This accumulation of calcium leads to microtubule collapse and excessive phosphorylation of the microtubule-associated protein tau, which is involved in the stabilization of the structure of axons and dendrites [ 103 , 104 ]. Recent studies have established an interaction between elevated calcium levels, autophagy, and synaptic denervation in the pathogenesis of AIP [ 90 , 91 , 105 ]. Elevated calcium and glutamate concentrations, combined with low serum vitamin D3 levels, are associated with the risk of developing parkinsonism and other neurodegenerative diseases [ 106 , 107 , 108 ].…”