Managing Musculoskeletal and Kidney Aging: A Call for Holistic Insights

Abstract

Aging represents a major concern, with a two-fold increase in individuals >65 years old by 2040. Older patients experience multiple declines in condition, with overlapping concerns. Fractures, frailty and falls remain underestimated events in routine practice. They are shared by numerous conditions and diseases, such as osteoporosis, sarcopenia and undernutrition, which mostly feature low evolution and are silent. In this review, we focused on musculoskeletal decline in older individuals who also have chronic kidney disease (CKD), which promotes fractures and falls. We aimed to highlight the need for a global approach for musculoskeletal and kidney aging. Although strategies limiting falls remain controversial, the need for an early diagnosis can limit these declines and allow for specific treatment of bone fragility in addition to non-pharmacological approaches. The emergence of senolytic agents offers new hope for preventing musculoskeletal disorders. This scoping review describes these overlapping silent diseases, provides evidence for their global understanding and management, and sheds light on new therapeutic directions.

Keywords: kidney disease; older individuals; osteoporosis; sarcopenia; senolytics.

Figure 1

Examples of dual energy X-ray absorptiometry scans illustrating the limitations of the measurement at the lumbar spine. These examples illustrate frequent limitations encountered in the assessment of dual energy X-ray absorptiometry scans in older patients. Yellow arrows point out osteophytes and bone calcification in the blue squared lumbar spine picture. (A) Blue frame: The blue table related to the blue frame picture underline the impact in overestimation of BMD with osteoarthritis at lumbar spine. (B) Green frame: These figure point out the important aortic calcification in vertebral assessment picture, leading to conclude to normal BMD shown in the green frame table. (C) Red squared pictures emphasize the presence of an unseen vertebral fracture at the first lumbar vertebra (Genant II-stage). In the associated dual energy X-ray absorptiometry scan, this fracture was not suspected, so BMD was overestimated in L1 compared to L2.

Figure 2

Interactions between musculoskeletal settings in older patients with chronic kidney disease. Plain frame represents diseases, and the other frames are parameters clinically assessed. This figure represents connections and interactions between phenotypes, diseases whatever the severity of each condition, in order to emphasize the key feature that fracture is, and therefore that falls and frailty must be prevented with an integrative management of all these diseases.

Figure 3

Current approaches in research on senolytics. This figure illustrates different pathways currently known as involved in cellular senescence. Modified metabolism in senescent cells can be identified with the SASP production. Senosuppressors mostly target the SASP secretion, whereas senomorphics limit cell cycle deregulation and oxidative stress. Senolytics also target the apoptosis resistance dysregulation.