Background
Bone is a plastic tissue that is responsive to its physical environment. As a result, exercise interventions have the potential to impact bone via a range of direct and indirect mechanisms [
1‐
3]. These include the direct impact of physical activity-induced loading cycles [
4], activity-specific metabolic signals such as alterations to calcium kinetics [
5], redox balance [
6], pH perturbations [
7], and indirect signals mediated via other tissues, primarily skeletal muscle [
8]. Substantial research and public resources are expended on investigating and implementing exercise-based interventions for populations who are susceptible to bone-related disorders. In general, activities that convey higher-impact, multi-directional, and unaccustomed loading patterns are considered to convey the greatest osteogenic stimulus, and for this reason, guidelines for the use of exercise to improve bone generally recommend that both resistance and impact-based modalities are employed [
9‐
11]. This approach has been reported to be effective in many populations, with meta-analytic data reporting a positive effect of controlled exercise interventions on bone density in a range of populations that include pre- [
12] and postmenopausal [
13] women, older adults [
14], individuals with osteoporosis [
15], and children [
16]. However, it is important to understand that several of the aforementioned meta-analyses included a number of studies that reported no effect of exercise on the bone, while some studies even suggest that the bone may be negatively impacted by very high volumes or intensities of exercise, e.g., in athletes competing in sports that emphasize leanness or those that rely upon repetitive loading cycles [
17‐
20].
Currently, there is a lack of understanding regarding the mechanistic pathways through which the bone responds to exercise. As a result, the identification of what combination of participant and exercise characteristics determine whether an osteogenic, osteoneutral, or even an osteolytic effect will be induced remains elusive. Acute exercise interventions are commonly used as an in vivo model to investigate the bone response to exercise, and these types of interventions have much to contribute to advancing the understanding of the processes through which the bone responds to exercise (and other acute stimuli). Bone remodeling is the dominant process through which mature bone responds to exercise [
21], and it comprises a sequential and synchronized process of bone activation, resorption, reversal, and formation [
3,
22]. Circulating bone biomarkers, which are widely used in the clinical setting [
23‐
25], are used to provide information on the dynamic state of bone remodeling. This is important because static indicators of bone health and function, such as bone mass measured by DXA, or microarchitecture as indicated by computed tomography or magnetic resonance imaging, are slow to respond to stimuli, with measurable changes taking months or even years to occur [
26]. As a result, bone biomarkers which are capable of providing more immediate information on the current bone state are the only viable option available to evaluate the impact of controlled, acute, exercise interventions on bone metabolism and, thus, to help identify the pathways that influence this response.
Recently, our research group published a comprehensive narrative review; the intention of which was to synthesize and evaluate our current understanding of the bone metabolic response to exercise [
21]. In that review, we observed that a single exercise session often elicits an increase in biomarkers that are indicative of bone resorption [
27‐
30], indicating an initial catabolic response of bone to exercise. In contrast, longer-term adaptations to exercise training are often characterized by an increase in bone formation markers [
31‐
39] that occur concurrently with positive changes in the bone mass or microarchitecture [
36,
40‐
42]. These observations appear plausible when considered in the context of what is suggested about the bone remodeling cycle, whereby the initial osteoclastic activation may be required to trigger a subsequent increase in osteoblastic activity [
22]. In order to further advance our understanding beyond these general observations, it is necessary to progress beyond dichotomous interpretations of increases/decreases/no changes in isolated bone biomarkers and instead consider the magnitude and context of the reported changes. However, this is challenging as considerable heterogeneity in research findings exists, most likely due to the large variation in the design, characteristics, and quality of available studies. Appropriate systematic review protocols and meta-analytic models are essential to overcome these challenges. However, to the best of our knowledge, no systematic review, with or without meta-analysis, has been conducted on this topic. Thus, the aim of this investigation is to use the systematic review and meta-analytic approach to quantify the effect of an acute bout of exercise on circulating biomarkers indicative of the bone metabolism, as well as investigate potential the factors that may moderate this response, e.g., variation in participant, exercise, and sampling characteristics.
Conclusions
A better understanding of the bone metabolic response to acute exercise has the potential to advance our understanding of the mechanisms through which this stimulus impacts bone metabolism. The comprehensiveness of the review will also allow identification of current gaps in the evidence base and subsequent recommendations to inform future research. Broadly, these recommendations will include the identification of pertinent research questions that are currently under-studied as well as the highlighting of methodological issues that were apparent across the evidence base as a whole, and which should be corrected to improve future research efforts. For example, although this analysis will consider all biomarkers that are suggested to effect bone metabolism, many of these are non-specific to the bone and/or are difficult to measure. As a result, we expect that the current analysis will provide insight as to which of these markers are most likely to effect exercise-induced changes in bone metabolism and, thus, will help to guide future research in this area. Finally, the results of this investigation will be disseminated via a presentation at relevant conferences and publications in peer-reviewed journals, serving as a contemporary foundation on which on-going research efforts in this topic can be based.
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