Novel techniques to determine the effects of exercise on bone turnover

Civil i Viñallonga, R., 2022. Novel techniques to determine the effects of exercise on bone turnover. PhD, Nottingham Trent University.


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Understanding bone (re)modelling in health and disease and developing interventions (e.g., exercise) to prevent the weakening of bone tissue across the lifespan is vital to preserve or improve bone health. While changes in the mineralised compartment of bone can be determined over prolonged periods (e.g., months/years), there are a lack of robust methods to study the short-term (days-weeks) physiology of bone collagen turnover, a key aspect of bone strength. As such, there is little understanding of the bone responses to acute interventions, such as exercise.

Indirect measures of bone formation and resorption can be made from the blood by certain biomarkers, but the utility of these markers to determine responses to acute and prolonged exercise interventions is unclear. The first study of this programme of work, reported in Chapter 3, was a systematic review and individual participant data meta-analysis investigating the mean responses and inter-individual variability of reference bone (re)modelling markers (P1NP and β-CTX-1) to a prolonged, continuous running bout in healthy adult males. This study determined that, when measured by reference bone (re)modelling markers, a single running bout does not elicit short-term bone responses in adult healthy males. The utility of this approach to measure short-term changes in bone (re)modelling in response to exercise is not well established and there is a need for alternative methods for studying the dynamic physiology of human bone turnover.

One of these alternative approaches might come from directly measuring bone protein synthesis in vivo, which can be carried out using stable isotopically labelled tracers, generally regarded as the gold standard in determining protein fractional synthetic rates, and can be performed on bone if a tissue sample can be collected. As such, in the next two studies, described in Chapters 4 and 5, a bone collagen extraction method and a new deuterium oxide (D2O) tracer method able to quantify bone collagen synthesis were developed and optimised using a rodent model, showing future applicability to human investigations.

Using the D2O method, different rates of bone collagen synthesis were determined across specific loaded bone sites (femur diaphysis, proximal tibia, mid-shaft tibia, distal tibia) in a rat model. Bone collagen synthesis rates were greater at the femur diaphysis than at the tibial mid-shaft and the proximal tibia showed greater synthesis compared to the tibial mid-shaft and distal tibia. Furthermore, the following studies, reported in Chapters 6 and 7, investigated the effects of age, phenotype, sex and running training on bone collagen synthesis in young and old rats. Age comparisons determined that older rats had slower bone collagen synthesis than young rats at the proximal tibia. Phenotype, sex and running training effects differed depending upon the site of measurement, showing that running training increased bone collagen formation at the mid-shaft and distal tibia. As an exploratory study, the last study (described in Chapter 8), examined the expression of bone remodelling and collagen genes and their associations with bone collagen formation, providing evidence that the expression of osteocalcin, osteoprotegerin and transforming growth factor β genes was linked to bone formation.

Collective evidence from this thesis highlights that bone responses are site-specific and that the complex structure of bone should be carefully considered when studying bone (re)modelling responses to loading. The geometry (i.e., size and shape) and microarchitecture (i.e., trabecular and cortical internal structure) of bone is not homogenous across long bones and modelling and remodelling processes are tailored to specific areas of the bone surface to optimise bone adaptations.

Item Type: Thesis
Creators: Civil i Viñallonga, R.
Date: 2022
Rights: This work is the intellectual property of the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the owner of the Intellectual Property Rights.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 25 Apr 2023 09:02
Last Modified: 25 Apr 2023 09:02

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