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. 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.Seven databases were systematically searched in accordance with pre-defined eligibility criteria. Bayesian threelevel hierarchical meta-analysis models were used to explore main effects of acute exercise on bone biomarkers, as well as potential moderating factors. Modelled effect sizes were interpreted according to three metrics namely: A) Evidence of an effect (defined by whether, or how much of, the 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.

Background Bone is a plastic tissue that is responsive to its physical environment. As a result, exercise interventions represent a potential means to influence the bone. However, little is currently known about how various exercise and participant characteristics interact to influence bone metabolism. Acute, controlled, interventions provide an in vivo model through which the acute bone response to exercise can be investigated, typically by monitoring circulating bone biomarkers. Currently, substantial heterogeneity in factors such as study design, quality, exercise, and participant characteristics render it difficult to synthesize and evaluate the available evidence. Using a systematic review and meta-analytic approach, the aim of this investigation is to quantify the effect of an acute exercise bout on circulating bone biomarkers as well as examine the potential factors that may moderate this response, e.g., variation in participant, exercise, and sampling characteristics. Methods This protocol was designed in accordance with the PRISMA-P guidelines. Seven databases (MEDLINE, Embase, Sport Discus, Cochrane CENTRAL, PEDro, LILACS, and Ibec) will be systematically searched and supplemented by a secondary screening of the reference lists of all included articles. The PICOS (Population, Intervention, Comparator, Outcomes and Study Design) approach was used to guide the determination of the eligibility criteria. Participants of any age, sex, training, or health status will be considered for inclusion. We will select studies that have measured the bone biomarker response before and after an acute exercise session. All biomarkers considered to represent the bone metabolism will be considered for inclusion, and sensitivity analyses will be conducted using reference biomarkers for the measurement of bone resorption and formation (namely β-CTX-1 and P1NP). Multi-level, meta-regression models within a Bayesian framework will be used to explore the main effect of acute exercise on bone biomarkers as well as potential moderating factors. The risk of bias for each individual study will be evaluated using a modified version of the Downs and Black checklist while certainty in resultant outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion A better understanding of the bone metabolic response to an acute bout of exercise has the potential to advance our understanding of the mechanisms through which this stimulus impacts bone metabolism, including factors that may moderate this response. Additionally, we will identify current gaps in the evidence base and provide recommendations to inform future research. Systematic review registration This protocol was prospectively registered in the Open Science Framework Registry (https://osf.io/6f8dz)

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