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The Bone Biomarker Response to an Acute Bout of Exercise: A Systematic Review with Meta-Analysis

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Abstract

Background

Circulating biomarkers are often used to investigate the bone response to an acute bout of exercise, but heterogeneity in factors such as study design, quality, selected biomarkers, and exercise and participant characteristics render it difficult to synthesize and evaluate available evidence.

Objective

The aim of this study was to quantify the effects of an acute exercise bout on bone biomarkers, along with the influence of potential moderators such as participant, exercise, and design characteristics, using a systematic review and meta-analytic approach.

Methods

The protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines and prospectively published. Seven databases were systematically searched in accordance with predefined eligibility criteria. Bayesian three-level hierarchical meta-analysis models were used to explore the main effects of acute exercise on bone biomarkers, as well as potential moderating factors. Modelled effect sizes were interpreted according to three metrics, namely (1) evidence of an effect (defined by whether, or how much of, the credible interval [CrI] included zero); (b) the size of that effect (threshold values of 0.01, 0.2, 0.5 and 0.8 were used to describe effect sizes as very small, small, medium and large, respectively); and (c) the level of certainty in the estimated effect (defined using the GRADE framework).

Results

Pooling of outcomes across all designs and categories indicated that an acute bout of exercise increased bone resorption (ES0.5 0.10, 95% CrI 0.00–0.20) and formation (ES0.5 0.05, 95% CrI 0.01–0.08) markers but the effects were very small and highly variable. Furthermore, moderator analyses revealed the source of some of this variability and indicated that exercise type and impact loading influenced the bone resorptive response. A moderate increase in C-terminal telopeptide of type 1 collagen (CTX-1) was observed in response to cycling (ES0.5 0.65, 95% CrI 0.20–0.99), with greater durations and more work leading to larger CTX-1 increases. CTX-1 response peaked within 15 min and 2 h after the exercise bout. Other exercise types did not influence CTX-1. Changes to all bone formation markers were very small and transient, with the very small increases returning to baseline within 15 min of exercise cessation. No major trends for bone formation markers were identified across any of the moderating categories investigated. Certainty of evidence in most outcomes was deemed to be low or very low.

Conclusion

The large influence of an acute bout of prolonged cycling on the bone resorption marker CTX-1, alongside the lack of a response of any biomarker to resistance or high-impact exercise types, indicate that these biomarkers may be more useful at investigating potentially osteolytic aspects of exercise, and raises questions about their suitability to investigate the osteogenic potential of different exercise types, at least in the short term and in response to a single exercise bout. Certainty in all outcomes was low or very low, due to factors including risk of bias, lack of non-exercise controls, inconsistency, imprecision and small-study effects.

Protocol Registration and Publication

This investigation was prospectively registered on the Open Science Framework Registry (https://osf.io/6f8dz) and the full protocol underwent peer review prior to conducting the investigation.

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Correspondence to Eimear Dolan.

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Funding

ED is financially supported by the Fundação de Ampara a Pesquisa do Estado do São Paulo (FAPESP: 2019/05616-6 and 2019/26899-6). No other sources of funding were used to assist in the preparation of this article.

Conflict of interest

Eimear Dolan, Alina Dumas, Karen M. Keane, Giulia Bestetti, Luisa Helena Mavalli Freitas, Bruno Gualano, Wendy M. Kohrt, George A. Kelley, Rosa Maria Rodrigues Pereira, Craig Sale and Paul A. Swinton declare that they have no conflicts of interest relevant to the content of this review.

Author contributions

ED and CS conceived the original idea for this article and the protocol was developed by ED, PAS, CS and GAK, with ongoing critical input from WMK, BG and RMRP. ED conducted the searches and ED, AD and KK selected the studies. Data were extracted by ED, AD, GB and LHMF. ED, AD and KK evaluated the risk of bias of each study, and PAS conducted all statistical analyses, with ongoing critical input from GEK. ED wrote the initial manuscript draft, which was then edited in accordance with ongoing critical input from all authors. All authors read and approved the final manuscript.

Data availability statement

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Dolan, E., Dumas, A., Keane, K.M. et al. The Bone Biomarker Response to an Acute Bout of Exercise: A Systematic Review with Meta-Analysis. Sports Med 52, 2889–2908 (2022). https://doi.org/10.1007/s40279-022-01718-8

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