The effect of loading context on bone’s deficient adaptive response to mechanical loading in old mice

  • Peter Delisser

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Normal bone maintains its ability to resist failure by adapting to the strain environment experienced by habitual activity. This adaptive process begins failing with advancing age, and subsequently bone loss occurs despite ongoing activity. This thesis reports experiments designed to investigate the effect of altering the context within which mechanical loading is applied on the adaptive loading response in old mice. These contextual changes include treatment with pharmaceuticals and changes in the level of background activity.
Although there is evidence that RANKL produced by osteocytes is essential for the bone loss associated with disuse, we were unable to identify any changes in the level of expression of RANKL in cortical bone osteocytes, using either qPCR or immunohistochemistry following either increased mechanical loading, or disuse.
Studies exploring the effect of altered context within which loading is applied found that preceding loading with a short period of disuse was sufficient to “rescue” the adaptive response to loading in old (19-months) female mice. Administration of the anti-resorptive risedronate (RIS) did not impair the loading response in old female mice, suggesting that loading, like in young mice is primarily mediated through bone modelling. Furthermore, the disuse-associated “rescue” was not affected by the concurrent administration of risedronate, suggesting that the mechanism involved is probably related to alterations in the strain environment, rather than being associated with any enhancement of bone remodelling following disuse.
Finally, the potent anabolic treatment, parathyroid hormone (PTH) was able to promote a strong anabolic response in very old (22-months) mice, which was not impaired by concurrent treatment with RIS, and resulted in additive gains in bone mass compared to vehicle treated mice. The loading response in 22-month-old mice was further impaired when compared to 19-month-old mice. This loading response was essentially unaffected by concurrent treatment with PTH and/or RIS.
Date of Award23 Jan 2019
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorJoanna Price (Supervisor) & John F Tarlton (Supervisor)

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