In vivo static creep loading of the rat forelimb reduces ulnar structural properties at time-zero and induces damage-dependent woven bone formation

Abstract

Periosteal woven bone forms in response to stress fractures and pathological overload. The mechanical factors that regulate woven bone formation are poorly understood. Fatigue loading of the rat ulna triggers a woven bone response in proportion to the level of applied fatigue displacement. However, because fatigue produces damage by application of cyclic loading it is unclear if the osteogenic response is due to bone damage (injury response) or dynamic strain (adaptive response). Creep loading, in contrast to fatigue, involves application of a static force. Our objectives were to use static creep loading of the rat forelimb to produce discrete levels of ulnar damage, and subsequently to determine the bone response over time. We hypothesized that 1) increases in applied displacement during loading correspond to ulnae with increased crack number, length and extent, as well as decreased mechanical properties; and 2) in vivo creep loading stimulates a damage-dependent dose-response in periosteal woven bone formation. Creep loading of the rat forelimb to progressive levels of sub-fracture displacement led to progressive bone damage (cracks) and loss of whole-bone mechanical properties (especially stiffness) at time-zero. For example, loading to 60% of fracture displacement caused a 60% loss of ulnar stiffness and a 25% loss of strength. Survival experiments showed that woven bone formed in a dose-dependent manner, with greater amounts of woven bone in ulnae that were loaded to higher displacements. Furthermore, after 14 days the mechanical properties of the loaded limb were equal or superior to control, indicating functional repair of the initial damage. We conclude that bone damage created without dynamic strain triggers a woven bone response, and thus infer that the woven bone response reported after fatigue loading and in stress fractures is in large part a response to bone damage.

Vertebral deformity arising from an accelerated “creep” mechanism

“…We suggest that a combined aetiology is most likely, because minor vertebral injuries are naturally more likely to occur than major ones. We speculate that each minor injury would be followed by accelerated creep for a period of days or weeks, before cellmediated healing processes would (partially) restore the bone's mechanical properties [41]. Vulnerable patients should perhaps be advised to minimize the time they spend in a stooped posture, because spinal flexion concentrates loading on to the anterior vertebral body, especially when the intervertebral discs are degenerated [42].…”

Osteocyte expression of caspase-3, COX-2, IL-6 and sclerostin are spatially and temporally associated following stress fracture initiation

“…The magnitude of the woven bone response is also damage dependant 16. Its repair has been described as a process of intramembranous fracture repair, with the induction of genes associated with angiogenesis, cell proliferation and osteoblastogenesis 12.…”

Physiologic load-bearing characteristics of autografts, allografts, and polymer-based scaffolds in a critical sized segmental defect of long bone: an experimental study

“…16,17 In our study, rat femoral repairs were evaluated postoperatively with radiographs and noninvasive dynamic mechanical analysis, which simultaneously assessed the elastic and viscoelastic properties of bone under low amplitude physiologic cyclic loading. [18][19][20][21][22] Our objective was to compare cyclic load-bearing characteristics and radiographic outcomes of each repair type.…”