The Histological Appearance of Stress Fractures

Mori, Satoshi; Li, Jiliang; Kawaguchi, Yoji

doi:10.1201/9781420042191.ch10

Cited by 17 publications

(26 citation statements)

References 17 publications

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“…Bone fatigue can lead to stress fractures, which are common in athletes and military recruits [1,24]. Histologically, stress fractures are associated with localized intracortical remodeling and periosteal woven bone formation [16,20], findings that are also observed in the rat ulna after a bout of damaging fatigue loading [2,15,25].…”

Section: Introductionmentioning

confidence: 80%

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

Lynch

Silva

2008

Bone

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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.

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Section: Introductionmentioning

confidence: 80%

“…Rats were assigned to eight sub-fracture displacement groups (20,30,40, 50, 60, 70, 80 and 90%; n = 7-11 per group). Right forelimbs were loaded until the displacement reached the prescribed stopping displacement (X% of the average displacement to fracture).…”

Section: Loading-induced Damagementioning

confidence: 99%

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

Lynch

Silva

2008

Bone

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“…Periosteal callus formation is a common radiological finding associated with a healing stress fracture, 3 and histological evidence from clinical subjects indicates that the callus is comprised of woven bone. [4][5][6] Based on our findings in rats, we hypothesize that this woven bone, short-term ''repair'' of the stress fracture not only corrects any whole-bone strength deficit associated with the stress fracture, but reduces the chances that another stress fracture will develop at that site. This structural repair should enable the patient to return to normal activities even while the intracortical damage associated with the stress fracture undergoes repair by osteonal remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…Periosteal callus formation (i.e., a localized thickening of the cortex) is a common radiological finding associated with a healing stress fracture. 3 Histological evidence from clinical subjects [4][5][6] and animal models [7][8][9] indicates that the callus is comprised of woven bone. (Woven bone, also referred to as ''immature bone,'' is commonly seen during development, fracture healing, and pathological conditions of high bone turnover.…”

Section: Introductionmentioning

confidence: 99%

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

Silva¹,

Touhey²

2006

Journal Orthopaedic Research

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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

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“…MRI evidence for excessive resorption at the site of atypical fractures also has been reported in a BP-treated patient, (12) and the same phenomenon has been seen in young athletes with early tibial stress injuries. (147,148) Somford and colleagues (11) also took the opportunity to assess the mineralization density of the bone tissue at the fracture site because some have suggested that prolonged BP treatment may lead to hypermineralized and, therefore, brittle bone matrix. There was no evidence of hypermineralization and no change in hydroxyapatite crystal size, although the crystals were more mature than in control subjects, consistent with the known effects of alendronate on bone turnover and secondary mineralization.…”

Section: Atypical Subtrochanteric and Femoral Shaft Fractures: Clinicmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

986

679

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Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

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The Histological Appearance of Stress Fractures

Cited by 17 publications

References 17 publications

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

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

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

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

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