The Bone Biomarker Response to an Acute Bout of Exercise
A Systematic Review with Meta-Analysis
DOI:
https://doi.org/10.51224/SRXIV.115Keywords:
exercise, bone, loading, remodeling, resorption, formation, meta-analysis, systematic reviewAbstract
Circulating biomarkers are 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. PURPOSE: 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 PRISMA-P guidelines and prospectively published [1]. Seven databases were systematically searched in accordance with pre-defined eligibility criteria. Bayesian three-level hierarchical meta-analysis models were used to explore main effects of acute exercise on bone biomarkers, as well as potential moderating factors. Risk of bias for each individual study was evaluated using a modified version of the Downs and Black checklist, while certainty in each meta-analytic outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Modelled effect sizes were interpreted according to three metrics including: A) Evidence of an effect (defined by whether, or how much of, the CrI included zero); B) The size of that effect (defined by standard categories, namely 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: Across all designs and categories, a very small effect of exercise on markers of bone resorption (ES0.5=0.10 [95%CrI: 0.00 to 0.21] and formation (ES0.5=0.06 [95%CrI: 0.02 to 0.09] was found. Moderator analyses indicated that exercise type and impact loading influenced results, with a large effect identified for the bone resorption marker CTX-1 in response to long-duration cycling (ES0.5=0.86 [95%CrI: 0.31 to 1.4]). The largest increases in CTX-1 occurred within 2 hours of exercise cessation. Exercise duration, intensity, and total work performed were also found to influence the bone biomarker response, albeit to a smaller degree. Certainty of evidence in most outcomes was deemed to be low or very low. CONCLUSION: Markers of bone resorption were most responsive to exercise and this was strongly influenced by exercise type and duration. Long-duration cycling induced a large effect on the resorption marker CTX-1, while other exercise types did not induce a response. All effects related to bone formation markers were very small and transient, calling into question the veracity and physiological relevance of these findings. The lack of a response to resistance or high impact exercise types indicate that these biomarkers may be more useful at investigating potentially osteolytic aspects of exercise, rather than its osteogenic potential. 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. Better control and standardization of future studies is required to increase certainty in results, and thus to advance understanding of the acute influence of exercise on bone.
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Copyright (c) 2022 Eimear Dolan, Alina Dumas, Karen M. Keane, Giulia C. Bestetti, Luisa HM Freitas, Bruno Gualano, Wendy M. Kohrt, George A. Kelley, Rosa M.R. Pereira, Craig Sale, Paul A. Swinton
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