Influence of Intrinsic Aerobic Exercise Capacity on Skeletal Health

Abstract

Low aerobic exercise capacity strongly associates with greater cardiovascular disease, increased incidence of metabolic syndrome, poor adaptation response to negative health environments, and weakened tissue repair. A greater capacity to sense, utilize, and optimize oxygen may represent a dominant factor in overall health and resistance to disease1-3. Bone cells are particularly responsive to their local oxygen environment, and therefore may demonstrate features as a reflection of aerobic capacity. PURPOSE: To determine the role of aerobic capacity on skeletal health, bone repair, and response to hormone withdrawal. METHODS: Experiments were performed using a rat model4 selectively bred for high (HCR) and low (LCR) intrinsic aerobic capacity that demonstrates a six-fold difference in treadmill running to exhaustion in the untrained condition. Bone morphology and mechanical properties were assessed in HCR (n = 10) and LCR (n = 9), and effect of exercise was tested in treadmill-trained LCR (LCR+TR; n = 11). Fracture repair, along with mesenchymal stem cell (MSC) proliferation, differentiation, and mineralization were assessed in HCR (n = 7) and LCR (n = 7) using femoral osteotomy and in vitro marrow cell assays. Response to estrogen withdrawal was evaluated to model postmenopausal osteoporosis (n = 12 HCR; n = 12 LCR). RESULTS: Exercise capacity of LCR+TR improved 36% above LCR (338 vs. 249 m; p < 0.05), but not to HCR levels (1731 m). HCR had smaller femora (p < 0.001), but elevated cortical tissue mineral density and Young's modulus (p < 0.01). Fracture callus size normalized by body mass was greater in HCR relative to LCR (p < 0.01), and improved healing corresponded with increased mineralization capacity of MSC's as measured in vitro. HCRs were protected against ovariectomy-induced bone loss at the femoral neck, but not at the proximal tibial metaphysis, reflecting site-specific bone loss. CONCLUSION: Results demonstrated that the intrinsic ability of bone cells to metabolize oxygen has a significant effect on phenotype, and suggest that aerobic capacity is an important regulator of bone health. (1) Gonzalez 2006 J Appl Physiol 101:1288. (2) Howlett 2008 J Appl Physiol 106:1819. (3) Morris 2009 Am J Nephrol 30:112. (4) Koch and Britton 2001 Physiol Genomics 5:45.