Relationship between osteoporosis and benign paroxysmal positional vertigo based on evidence-based medicine and bioinformatics

Abstract

It has been reported that osteoporosis is a possible risk factor of benign paroxysmal positional vertigo (BPPV).

Purpose: We analyzed the correlation between osteoporosis and BPPV and the possible mechanism by performing evidence-based medicine meta-analysis and bioinformatics analysis.

Methods: Initially, English articles related to osteoporosis and BPPV were obtained through PubMed and EMBASE databases. Stata12.0 software was used for meta-analysis to calculate the odd ratio (OR) and 95% confidence interval (CI) of outcome indicators, and the heterogeneity was evaluated by subgroup analysis, publication bias evaluation, and sensitivity analysis. In addition, microarray datasets related to BPPV and osteoporosis were obtained from gene expression omnibus (GEO) database to screen differentially expressed genes. At last, a mouse model of osteoporosis was established by bilateral oophorectomy for validation. RT-qPCR and Western blot analysis were performed to determine expression of related factors in mouse tissues.

Results: Osteoporosis was suggested as an important risk factor for BPPV through meta-analysis of these 12 articles. It was found that PPP2CA was upregulated in BPPV and low bone mineral density (BMD) samples. Moreover, PPP2CA induced dephosphorylation of BCL2, which may be involved in BPPV through regulation of BMD. Through this mechanism, silencing of PPP2CA could elevate the incidence of BPPV by promoting bone remodeling and reducing the density of otoconia around the macula.

Conclusions: PPP2CA reduces BMD expression by inducing dephosphorylation of BCL2, which may be one of the mechanisms responsible for the onset of BPPV in osteoporosis.

Keywords: BCL2; Benign paroxysmal positional vertigo; Dephosphorylation; Evidence-based medicine; Meta-analysis; Osteoporosis; PPP2CA.