Pathogenesis of Age-Related Osteoporosis: Impaired Mechano-Responsiveness of Bone Is Not the Culprit

Background: According to prevailing understanding, skeletal mechano-responsiveness declines with age and this apparent failure of the mechano-sensory feedback system has been attributed to the gradual bone loss with aging (age-related osteoporosis). The objective of this study was to evaluate whether the capacity of senescent skeleton to respond to increased loading is indeed reduced as compared to young mature skeleton. Methods and Findings: 108 male and 101 female rats were randomly assigned into Exercise and Control groups. Exercise groups were subjected to treadmill training either at peak bone mass between 47-61 weeks of age ( Mature) or at senescence between 75-102 weeks of age ( Senescent). After the training intervention, femoral necks and diaphysis were evaluated with peripheral quantitative computed tomography (pQCT) and mechanical testing; the proximal tibia was assessed with microcomputed tomography (mu CT). The mu CT analysis revealed that the senescent bone tissue was structurally deteriorated compared to the mature bone tissue, confirming the existence of age-related osteoporosis. As regards the mechano-responsiveness, the used loading resulted in only marginal increases in the bones of the mature animals, while significant exercise-induced increases were observed virtually in all bone traits among the senescent rats. Conclusion: The bones of senescent rats displayed a clear ability to respond to an exercise regimen that failed to initiate an adaptive response in mature animals. Thus, our observations suggest that the pathogenesis of age-related osteoporosis is not attributable to impaired mechano-responsiveness of aging skeleton. It also seems that strengthening of even senescent bones is possible - naturally provided that safe and efficient training methods can be developed for the oldest old.