Bone mechanotransduction may require augmentation in order to strengthen the senescent skeleton

Abstract

Physical exercise is thought to hold promise as a non-invasive countermeasure against skeletal fragility arising from post-menopausal and age-related osteoporosis. Importantly, mechanical loading and exercise are capable of increasing bone size via periosteal expansion, which by far, is the most effective means of strengthening the structure of a given bone. The focus of this review was to therefore explore whether exercise has the potential to increase periosteal modeling and bone size in the senescent skeleton. A survey of exercise trials in humans suggests that exercise interventions that enhance periosteal modeling in the young skeleton fail to do the same in the elderly skeleton. Underlying this ineffectiveness, in vitro studies indicate that aging lowers basal levels of cell function and degrades bone mechanotransduction at a variety of levels from altered second messenger signaling to gene expression driving proliferation and/or differentiation. Given these age-related alterations, the ultimate efficacy of an exercise intervention may depend upon concurrent supplementation that directly address deficits in signaling and/or cell function. In this context, in vivo animal models of mechanical loading that simulate the muted periosteal adaptation in the elderly hold potential to examine the efficacy of countermeasures. Preliminary in vivo experiments suggest that pharmacologically counteracting age-related deficits in cellular function can restore exercise induced periosteal modeling in the senescent skeleton to levels observed in young animals. If the safety and efficacy of this strategy were to be confirmed for human use, it would enable the utilization of exercise as a viable countermeasure against skeletal fragility at senescence.

Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats

“…The mature HRLF rats failed to demonstrate osteogenesis (no change in osteocalcin or osteoblast numbers or activity) after task performance. This low osteogenic response in the mature HRLF rats is consistent with prior studies showing that more vigorous loading or longer loading periods may be necessary to induce an osteogenic response in aging mammals [38, 39, 74, 75]. Reports about how aging affects the osteogenic potential of mesenchymal cells are conflicting, with some studies stating that aging does not affect osteoblast recruitment, differentiation and activity [76], while others state that there is an age-related decline in the osteogenic potential of bone marrow cells [77] that can be improved by physical activity in rats [78].…”

“…In the mid-diaphyseal cortical bone of young adult HRLF rats, marrow area was decreased (indicative of growth at the endosteal surface), periosteal perimeter was the increased osteoclastic resorption (indicative of periosteal growth), cortical thickness was increased, and the cortical BMD was increased. Each are positive adaptive changes that should reduce the risk of bone fracture [39, 74]. The increased osteoblast numbers and activity and increased MAR and BFR in the young adult HRLF rats, compared to unloaded control rats, indicate an increase in bone formation in response to performance of this moderate level task for 12 weeks.…”

Age-Related Impairment of Bones' Adaptive Response to Loading in Mice Is Associated With Sex-Related Deficiencies in Osteoblasts but No Change in Osteocytes

“…Interventional exercise studies in humans suggest that bones' periosteal modeling response to exercise declines with age in both sexes,3 although elderly men appear more responsive than women 4,5. In vivo studies in female rodents also suggest impairment of the osteogenic response to a defined strain-related stimulus 6,7.…”

High impact exercise increased femoral neck bone mineral density in older men: A randomised unilateral intervention

“…Although older people are the population at most immediate risk of osteoporosis, it has been suggested that exercise may be less effective in older, than younger, people [6][7]. This may be related to the type and intensity of the exercise interventions studied, as lower neuromuscular function [8] or greater injury risk may limit exercise intensity in older people.…”