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Association between Osteoprotegerin and Charcot Neuroarthropathy: a systematic review

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Abstract

Aims

Osteoprotegerin (OPG) has been associated with Charcot Neuroarthropathy (CN); however, three studied OPG polymorphisms (1181C > G, 245A > C and 950 T > C) have yielded conflicting results. Therefore, this meta-analysis was conducted to determine the difference in serum OPG concentrations between healthy controls and diabetics with and without CN and the effect OPG polymorphisms have on CN development.

Methods

PubMed, LILAC, SCOPUS, and EBSCO databases and retrieved publications’ bibliographies were searched for studies that examined for OPG and CN. Depending on the heterogeneity, fixed or random effects were used to calculate the pooled odds ratio (OR) or standard difference in means (SDM) with 95% confidence intervals (95%CI) for 5 genetic models (heterozygous, homozygous, dominant, recessive, and allelic) and serum concentrations, respectively.

Results

Seven publications (12 studies) demonstrated that serum OPG concentrations were more elevated in subjects with CN (SDM = 0.719, 95%CI = 0.555–0.883, p < 0.001). When CN was compared to healthy controls or diabetics, the difference was more prominent for healthy controls (SDM = 1.043, 95%CI = 0.676–1.409, p < 0.001) than diabetics (SDM = 0.639, 95%CI = 0.456–0.821, p < 0.001) and the SDM difference was significant (p = 0.013). Using 6 publications (9 studies), neither the 1181C > G or the 950 T > C polymorphisms showed any significant associations for any genetic model. For the 245A > C polymorphism, only the homozygous genetic model showed a significant association between the polymorphism and CN (OR = 2.850, 95%CI: 1.051–7.729, p = 0.040).

Conclusions

Here, we determined a potential correlation between the CN and serum OPG concentrations and that only the CC genotype of the 245A > C polymorphism showed an increased risk of developing CN.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

The authors would like to express their gratitude to Mtro. Ricardo Villegas Tovar, Coordinator of Scientific Production and International Visibility, BUAP.

Funding

This study was supported by grants from the Programa para el Desarrollo Profesional Docente (to CA-160 FACMED) and the Vicerrectorıa de Investigacion, Benemerita Universidad Autonoma de Puebla, Mexico (to TORE-SAL19-G, PEFR-SAL19-G, and GOMM-SAL18-I).

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Author notes

  1. Renata Ochoa-Précoma and Blanca Teresa Pacheco-Soto have contributed equally.

Authors and Affiliations

  1. Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Calle 13 Sur 2901, Colonia Volcanes, 72420, Puebla, México

    Renata Ochoa-Précoma, Blanca T. Pacheco-Soto, Enrique Torres-Rasgado & M. Elba Gonzalez-Mejia

  2. Laboratorio de Fisiopatología en Enfermedades Crónicas, Centro de Investigación Biomédica de Oriente, IMSS. Delegación Puebla. Carretera Federal Atlixco Metepec Km, 4.5, Colonia Centro, 74360, Atlixco, Puebla, México

    Leonardo M. Porchia & Ricardo Pérez-Fuentes

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  1. Renata Ochoa-Précoma
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Correspondence to M. Elba Gonzalez-Mejia.

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Ochoa-Précoma, R., Pacheco-Soto, B.T., Porchia, L.M. et al. Association between Osteoprotegerin and Charcot Neuroarthropathy: a systematic review. Acta Diabetol 58, 475–484 (2021). https://doi.org/10.1007/s00592-020-01638-x

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