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Human Relevance of Preclinical Studies on the Skeletal Impact of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

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Abstract

Inflammatory bowel disease (IBD) is a relapsing chronic idiopathic inflammatory condition. The increased risks of fractures in the spine and decreased BMD at all weight-bearing skeletal sites have been reported in IBD patients. The understanding of the mechanisms of IBD-induced bone loss is far from complete. Appropriate animal models are a prerequisite for studying IBD-induced bone loss, which prompted us to undertake quantitative meta-analyses by pooling data from the available IBD models that assessed various bone parameters. Sufficient data for meta-analysis are obtained from chemically- but not genetically induced models. Among the chemically induced models, only the effects of dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) on bone parameters have been reported. Meta-analysis showed that both DSS (Hedge’s g = 2.124, p = 0.001) and TNBS (Hedge's g = 6.292, p = 0.000) increased inflammatory disease severity. In pooled analysis, bone volumes in femur (Hedge's g = − 3.42, p = 0.000) and tibia (Hedge's g = − 2.49, p = 0.000) showed significant losses upon DSS administration. Similarly, bone formation rate was significantly reduced upon IBD induction (Hedge’s g = − 3.495, p = 0.006). Besides, cortical thickness was reduced and trabecular microstructure deteriorated by IBD induction. Insufficient data precluded us from determining the effect of IBD on bone strength and calciotropic hormones, as well as the impact of proinflammatory cytokines on bone turnover. This meta-analysis showed that IBD induction in rodents causes significant bone loss. Impaired osteoblast function appears to be the cause of this impact.

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All data are available upon request.

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Funding

This study was supported by Central Drug Research Institute (Grant No. MLP117). Supporting grant: Council of Scientific and Industrial Research, Government of India. Swati Rajput would like to thank the Department of Biotechnology, Govt. of India for graduate fellowship (Ref No. DBT/2018/CDRI/1047). Poonam Mehta would like to thank the University Grants Commission for graduate fellowship (Ref. No. 460/CSIR-UGC NET DEC.2017). The CDRI communication number is 10182.

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  1. Swati Rajput and Poonam Mehta contributed equally to this study.

Authors and Affiliations

  1. Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India

    Swati Rajput, Poonam Mehta, Monika Mittal, Singh Rajender & Naibedya Chattopadhyay

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India

    Swati Rajput, Poonam Mehta, Singh Rajender & Naibedya Chattopadhyay

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  1. Swati Rajput
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Contributions

SR conducted literature screening and wrote the manuscript; PM performed statistical analyses of the extracted data; MM conducted literature screening and wrote the manuscript; SR conceived the idea, performed statistical analyses of data and wrote the manuscript; NC conceived the idea, conducted literature screening and wrote the manuscript.

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Correspondence to Singh Rajender or Naibedya Chattopadhyay.

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Swati Rajput, Poonam Mehta, Monika Mittal, Singh Rajender, and Naibedya Chattopadhyay declare that they have no conflict of interest.

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Rajput, S., Mehta, P., Mittal, M. et al. Human Relevance of Preclinical Studies on the Skeletal Impact of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Calcif Tissue Int 108, 708–724 (2021). https://doi.org/10.1007/s00223-021-00808-5

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