Bone formation after damaging in vivo fatigue loading results in recovery of whole‐bone monotonic strength and increased fatigue life

Abstract

Bone has a remarkable capacity for self-repair. We previously reported a woven bone response after damaging in vivo fatigue loading of the rat ulna that led to a rapid recovery of wholebone strength. In the current study we asked: does the bone response in the 12 days after damaging fatigue loading result in a bone that has normal fatigue properties? The right forelimbs of 52 adult rats were subjected to a single bout of in vivo fatigue loading. Nonloaded left forelimbs were used as controls. Ulnar geometric properties were assessed by peripheral quantitative computed tomography (pQCT) and ex vivo mechanical properties were assessed by three-point bending. On day 0, ulnae from loaded forelimbs had a 15-20% reduction in stiffness and ultimate force versus controls (p < 0.10), indicative of structural damage. On day 12, bone area at the midshaft was increased by 27% (p < 0.001) and microCT scans revealed periosteal woven bone at this site. This bone response led to a recovery of the monotonic properties of loaded ulnae at day 12 versus control (stiffness, p ¼ 0.73; ultimate force, p ¼ 0.96). Importantly, fatigue testing ex vivo at day 12 demonstrated significantly greater fatigue life in in vivo loaded ulnae versus controls (p < 0.001). Additionally, the slope of the fatigue-life curve was significantly less in loaded versus control ulnae (p < 0.002). We conclude that woven bone ''repair'' of a bone damaged by fatigue loading restores whole-bone strength and enhances resistance to further damage by repetitive loading. ß

Activation of bone remodeling after fatigue: Differential response to linear microcracks and diffuse damage

“…As the intracortical remodeling activated by microdamage stimulus originates principally from periosteal and endocortical surfaces, it is possible that the differential response to the microdamage types observed may also be influenced by location of the damage type. The linear microdamage observed in this study was located mostly in the compressively-loaded regions of the ulnar diaphysis (44, 69, 70) nearer to the periosteal surfaces, while the diffuse damage characteristically occurred in tensile-loaded regions of the ulnar cortex and was distributed throughout the cortex. However, in previous canine (9, 51) fatigue studies, both linear microdamage and the associated intracortical remodeling activity were observed away from bone surfaces, indicating that it is unlikely that location of microdamage plays a major role in governing the remodeling response to the overuse stimulus.…”

“…However, because of the high fatigue levels examined in their study, the ulnae possessed both damage types, making it impossible to separate completely the effects of these two damage types. In the current studies we built on the recent observations from our laboratory and others showing that small-crack-type (i.e., diffuse) damage occurs earlier in bone's fatigue loading history than linear microcracks and also in different areas from linear microcracks (3, 7, 21-23, 69, 70, 75). Diffuse damage leads to changes in local material properties.…”

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

“…32,33 In the current study, treatment with risedronate at high and low doses following stress fracture formation did not change the area or thickness of the woven bone. The woven bone in this model restores the mechanical properties of the ulna by 2 weeks after loading, 34,35 and this woven bone response was unaffected by risedronate treatment even at the high dose. Woven bone formation following rat ulnar loading was also unaffected by alendronate treatment given for 2 weeks prior to loading.…”

“…This woven bone response is able to return the ulna to its original strength within 2 weeks of stress fracture creation in the rat ulna loading model. 35,42 It is therefore possible that woven bone callus is able to protect the site of the fracture and reduce any detrimental effects of a delay in stress fracture remodeling in clinical stress fracture cases.…”

Selective and non‐selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna

“…In this model, woven bone formation restores whole-bone mechanical strength within 12 days of loading, well before SFx healing is complete. 28,29 Mechanical testing would only reflect major changes in woven bone formation that are independent of the remodeling process along the fracture line. 15,16 Mechanical testing of whole bones is therefore not usually used to evaluate crack healing and remodeling along the SFx in this model.…”