Decreased bone density induced by antiepileptic drugs can cause accelerated orthodontic tooth movement in male Wistar rats

Akhoundi, Mohammad Sadegh Ahmad; Sheikhzadeh, Sedigheh; Mirhashemi, Amir Hossein; Ansari, Elahe; Kheirandish, Yasaman; Allaedini, Mozhgan; Dehpour, Ahmad Reza

doi:10.1016/j.ortho.2018.01.021

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…It is noteworthy that long-term antiepileptic drug (AED) treatment can have side effects, including disorders of bone metabolism leading to bone loss. − The exact mechanism of this pathological change is not completely understood. It is commonly accepted that intact Wnt signaling is essential for proper bone formation and remodeling .…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8

et al. 2020

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Misregulation of Wnt signaling is common in human cancer. The development of small molecule inhibitors against the Wnt receptor, frizzled (FZD), may have potential in cancer therapy. During small molecule screens, we observed binding of carbamazepine to the cysteine-rich domain (CRD) of the Wnt receptor FZD8 using surface plasmon resonance (SPR). Cellular functional assays demonstrated that carbamazepine can suppress FZD8-mediated Wnt/β-catenin signaling. We determined the crystal structure of the complex at 1.7 Å resolution, which reveals that carbamazepine binds at a novel pocket on the FZD8 CRD. The unique residue Tyr52 discriminates FZD8 from the closely related FZD5 and other FZDs for carbamazepine binding. The first small molecule-bound FZD structure provides a basis for anti-FZD drug development. Furthermore, the observed carbamazepine-mediated Wnt signaling inhibition may help to explain the phenomenon of bone loss and increased adipogenesis in some patients during long-term carbamazepine treatment.

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Section: Discussionmentioning

confidence: 99%

Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8

et al. 2020

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“…The lower jaws skeletonized, sawed jaw blocks in the molar area. Bone mineral density was determined by optical densitometry, which is widely used in medicine [9,10,11,12]. For densitometric studies, radiovisiography of dental blocks was performed.…”

Section: Methodsmentioning

confidence: 99%

The State of the Optical Density of the Alveolar Process of the Jaws of Rats in Supraocclusive Relationships of Individual Teeth in the Age Aspect

2021

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The aim of the study was to conduct a comparative assessment of the optical density of bone tissue of the alveolar process of the jaws of rats in supraocclusive relationships of individual teeth in the age aspect. Materials and methods: The study was performed on 60 white laboratory rats. Rats were divided into control (30 individuals) and experimental (30 individuals) groups. According to the age of rats each group was divided into 3 subgroups (10 animals): young, mature and senile. In the experimental group, the state of supraocclusion was modeled by increasing the height of the lower right second molars placing a seal 1 mm high. Experimental animals were removed from the experiment on the 15th day through decapitation. The lower jaws were skeletonized, jaw blocks were sawn in the molar area. Bone mineral density was determined using optical densitometry. The statistical processing defined the average (M) and its error (m). The statistical significance of the difference in two independent groups was performed according to nonparametric criteria (Mann-Whitney U-test and W-Wilcoxon test). Statistical processing was conducted with the help of integrated package of statistical program AtteStat 12.0.5 for MS Excel. Differences at p≤ 0.05 were considered statistically significant. Results: Statistical discrepancy is present in rats of mature and senile age, as well as between the indicators of all rats of the control and experimental groups (≤0.05). No significant difference was observed in young rats, but the indicators of the experimental group were 3.82% worse than in the control group. In senile rats, the density of the alveolar process decreased by 26.6%, in adult rats by 17.5%. Conclusions: The presence of supraocclusive relationships of individual teeth causes a decrease in bone density of the alveolar process of the jaws in rats. The greatest loss of density among age groups in elderly rats.

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“…Previous studies have reported that VPA functions as a histone deacetylase inhibitor (HDACi), with the speci c inhibiting activity by binding to the catalytic centre of HDACs , which stimulate apoptosis and inhibit the proliferation of cancer cells [9]. Besides, VPA could cause tubular renal dysfunction and subsequent abnormal metabolism and loss of calcium and phosphorus [10]. Interestingly, clinical and animal experiments have shown the decreased bone mineral density(BMD) with VPA treatment [11,12], but some studies have failed to show such harmful effects on BMD [13,14], and even several cellular, and animal experiments have shown VPA's bene cial effects on bone health [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats

Tao

Zhou

et al. 2021

European Journal of Pharmacology

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Objective: the present work was aimed to evaluate the effect of different administration modes of sodium valproate(VPA) on bone strength, bone mass and bone mineral density in ovariectomized(OVX) rats and further investigation of the possible mechanism.Methods: 60 female SD rats were randomly divided into 4 groups: Sham group (Sham, n=15), OVX group (OVX, n=15), OVX rats received intermittent VPA treatment group(IVPA, n=15) and OVX rats received daily VPA treatment group(EVPA, n=15). After 12 weeks of treatment, the rats were sacri ced, and serum and femur samples were harvested. DEXA, Micro-CT, histology, biomechanical testing, biochemical index and western blot analysis were used to observe the therapeutic effect and explore the possible mechanism.Results: Micro-CT and DEXA analysis of bones revealed better BMD and higher BV/TV, Tb.Th, Tb.N, Conn. D and lower Tb.Sp at femoral metaphysis with evaluated in IVPA when compared with OVX and EVPA group(P 0.05). Histological, uorescent analysis and biological strength revealed more trabecular bone and higher relative mineral apposition rate, maximal load, elastic modulus and energy at break with evaluated in IVPA when compared with OVX and EVPA group(P 0.05). The levels of P1NP, estrogen, CTX, TRAP5b and RANKL of IVPA group showed a signi cant increase when compared with the OVX and EVPA group(P 0.05). We con rm adverse effects on protein expressions including Notch1, Jagged1, HEY1, Wnt 1, β-catenin and RUNX2 following daily VPA treatment in OVX female rats.Conclusions: Our current study demonstrated that intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats and these effects may be achieved by activating Notch/Wnt/β-catenin/ RUNX2 signal axis.

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Decreased bone density induced by antiepileptic drugs can cause accelerated orthodontic tooth movement in male Wistar rats

Cited by 4 publications

References 20 publications

Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8

Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8

The State of the Optical Density of the Alveolar Process of the Jaws of Rats in Supraocclusive Relationships of Individual Teeth in the Age Aspect

Intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats

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