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Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.

ABSTRACT: We developed a fatigue loading protocol in mice to produce a non-displaced ulnar fracture in vivo, and characterized the early healing response. Using adult (5 month) C57Bl/6 mice, we first determined that cyclic compression of the forelimb under load-control leads to increasing applied displacement and, eventually, complete fracture. We then subjected the right forelimbs of 80 mice to cyclic loading (2 Hz; peak force approximately 4N) and limited the displacement increase to 0.75 mm (60% of the average displacement increase at complete fracture). This fatigue protocol created a partial, non-displaced fracture through the medial cortex near the ulnar mid-shaft, and reduced ulnar strength and stiffness by >50%. Within 1 day, there was significant upregulation of genes related to hypoxia (Hif1a) and osteogenesis (Bmp2, Bsp) in loaded ulnae compared to non-loaded, contralateral controls. The gene expression response peaked in magnitude near day 7 (e.g., Osx upregulated 8-fold), and included upregulation of FGF-family genes (e.g., Fgfr3 up 6-fold). Histologically, a localized periosteal response was seen at the site of the fracture; by day 7 there was abundant periosteal woven bone surrounding a region of cartilage. From days 7 to 14, the woven bone became denser but did not increase in area. By day 14, the woven-bone response resulted in complete recovery of ulnar strength and stiffness, restoring mechanical properties to normal levels. In the future, the fatigue loading approach can be used create non-displaced bone fractures in transgenic and knockout mice to study the mechanisms by which the skeleton rapidly repairs damage.

SUBMITTER: Martinez MD

PROVIDER: S-EPMC2875275 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.

Martinez Mario D MD Schmid Gregory J GJ McKenzie Jennifer A JA Ornitz David M DM Silva Matthew J MJ

Bone 20100306 6

We developed a fatigue loading protocol in mice to produce a non-displaced ulnar fracture in vivo, and characterized the early healing response. Using adult (5 month) C57Bl/6 mice, we first determined that cyclic compression of the forelimb under load-control leads to increasing applied displacement and, eventually, complete fracture. We then subjected the right forelimbs of 80 mice to cyclic loading (2 Hz; peak force approximately 4N) and limited the displacement increase to 0.75 mm (60% of the ...[more]

PMID: 20215063

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Project description:Woven bone is formed in response to fatigue-induced stress fractures and is associated with increased local angiogenesis. The molecular mechanisms that regulate this woven bone formation are unknown. Our objective was to measure the temporal and spatial expression of osteo- and angiogenic genes in woven bone formation in response to increasing levels of fatigue-induced damage. We used the rat forelimb compression model to produce four discrete levels of fatigue damage in the right ulna of 115 male Fischer rats. Rats were killed at 0 (1 h), 1, 3 and 7 days after loading. Using qRT-PCR, we quantified gene expression associated with osteogenesis (BMP2, Msx2, Runx2, Osx, BSP, Osc), cell proliferation (Hist4), and angiogenesis (VEGF, PECAM-1) from the central half of the ulna. The spatial distribution of BMP2, BSP and PCNA was assessed by immunohistochemistry or in situ hybridization in transverse histological sections 1, 4, and 7 mm distal to the ulnar mid-diaphysis. One hour after loading, BMP2 was significantly upregulated in neurovascular structures in the medial ulnar periosteum. Expression of angiogenic markers (VEGF, PECAM-1) increased significantly between Day 0 and 1 and, as with BMP2 expression, remained upregulated through Day 7. While Osx and BSP were upregulated on Day 1, the other osteogenic genes (Msx2, Runx2, Osx, BSP and Osc) were induced on Day 3 in association with the initiation of periosteal woven bone formation and continued through Day 7. The magnitude of osteogenic gene expression, particularly matrix genes (BSP, Osc) was significantly proportional the level of fatigue damage. The woven bone response to fatigue injury is remarkably similar to the "intramembranous" portion of fracture repair - rapid formation of periosteal woven bone characterized by early BMP2 expression, cell proliferation, and upregulation of osteogenic genes. We speculate that woven bone repair of fatigue damage may be an abbreviated fracture response without the requirement for endochondral repair. We conclude that bone fatigue repair is a process similar to intramembranous fracture repair characterized by increases in the expression of genes associated with angiogenesis, cell proliferation and osteoblastogenesis, and that the response from the local vasculature precedes the osteogenic response to fatigue loading.

Project description:IntroductionGiven the absence of a satisfying plate system to deal with multifragmentary or subcapital distal ulnar fractures, the Distal Ulna Locking Plate (DUL, I.T.S. GmbH, Graz, Austria) could become a useful treatment option. This study aimed to evaluate the results of this anatomically pre-contoured plate regarding patients with unstable or displaced distal ulnar fractures.MethodsIn a prospective clinical trial, 20 patients (18 female, two male; mean age 70 years (24-91 years)) with unstable or displaced distal ulna fractures between December 2010 and August 2015 were analyzed. All patients were treated with open reduction and internal fixation using the DUL. They were evaluated at three follow-up appointments at 3, 6 and 12 months postoperatively regarding their bone healing, ulnar variance (UV), range of motion (ROM) and grip strength. Patient related outcomes were measured using the Disability of the Arm, Shoulder and Hand (DASH), the Patient Rated Wrist Evaluation (PRWE) questionnaires, and the Visual Analogue Scale (VAS). The results after one year were compared to the outcome of the healthy contralateral side.ResultsAll fractures treated with open reduction and internal fixation using the Distal Ulna Locking Plate healed within 6 months and showed stable ulnar variances after surgery. ROM (rotational plane 81.1 ± 9.0°, sagittal plane 55.1 ± 14.6°, frontal plane 33.0 ± 9.4°) and grip strength (18.7 ± 7.1 N) at the follow-up after 12 month had similar values compared with the uninjured side. The mean DASH score (36.4 ± 29.0), the PRWE-score (14.5 ± 27.0), and the VAS (at rest 0.5 ± 1.1, during activity 1.2 ± 2.4) after one year had no significant difference to the uninjured side. The surgeon's overall satisfaction rate regarding plate handling reached 81.8%.ConclusionStabilization of unstable distal ulna fractures using the DUL restores nearly normal anatomy and function. Its pre-countered design, volar placement, and enhanced stability present a satisfying plate system.Trial registration The trial was retrospectively Registered at www.Clinicaltrialsgov on 16 December 2021 (Trial Registration Number: NCT05329012).

Project description:BACKGROUND:Isolated fractures of the shaft of the ulna, which are often sustained when the forearm is raised to shield against a blow, are generally treated on an outpatient basis. This is an update of a Cochrane review first published in 1998 and last updated in 2009. OBJECTIVES:To assess the effects of various forms of treatment for isolated fractures of the ulnar shaft in adults. SEARCH METHODS:We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (April 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 3), MEDLINE (1966 to April week 1 2012), EMBASE (1981 to week 15 2012), CINAHL (1982 to 16 April 2012), various trial registers, various conference proceedings and bibliographies of relevant articles. SELECTION CRITERIA:Randomised or quasi-randomised trials of conservative and surgical treatment of isolated fractures of the ulnar shaft in adults. Excluded were fractures of the proximal ulna and Monteggia fracture dislocations. DATA COLLECTION AND ANALYSIS:We performed independent assessment of risk of bias and data extraction. We contacted trialists for more information. There was no pooling of data. MAIN RESULTS:The updated search resulted in the identification of one ongoing trial comparing surgery versus conservative treatment.Four trials, involving a total of 237 participants, were included. All four trials were methodologically flawed and potentially biased.Three trials tested conservative treatment interventions. One trial, which compared short arm (below elbow) pre-fabricated functional braces with long arm (elbow included) plaster casts, found there was no significant difference in the time it took for fracture union. Patient satisfaction and return to work during treatment were significantly better in the brace group. The other two trials, both quasi-randomised, had three treatment groups. One trial compared Ace Wrap elastic bandage versus short arm plaster cast versus long arm plaster cast. The large loss to follow-up in this trial makes any data analysis tentative. However, the need for replacement of the Ace wrap by other methods due to pain indicates the potential for a serious problem with this intervention. The other trial, which compared immediate mobilisation versus short arm plaster cast versus long arm plaster cast for minimally displaced fractures, found no significant differences in outcome between these three interventions.The fourth trial, which compared two types of plates for surgical fixation, found no significant differences in functional or anatomical outcomes nor complications between the two groups. AUTHORS' CONCLUSIONS:There is insufficient evidence from randomised trials to determine which method of treatment is the most appropriate for isolated fractures of the ulnar shaft in adults. Well designed and reported randomised trials of current forms of conservative treatment are recommended.

Project description:BackgroundSurgery for fixation of olecranon fractures is associated with reoperation, mostly for implant removal. A study of a large cohort of patients treated by many different surgeons allows us to determine if specific techniques or implants are associated with a higher rate of reoperation.Questions/purposesAfter open reduction and internal fixation of isolated olecranon fractures, what factors are associated with (1) reoperation and (2) implant removal?MethodsThree hundred ninety-two adult patients who had operative treatment of a displaced olecranon fracture not associated with other fractures, dislocation, or subluxation at two area hospitals between January 2002 and May 2014 were analyzed to determine factors associated with reoperation. One hundred thirty-eight (35%) patients had plate and screw fixation and 254 (65%) tension band wiring. Nearly 100% of patients with displaced olecranon fractures are currently treated operatively at our hospitals. All patients were followed for at least four months. Two hundred three of the 392 (52%) patients were followed for one year or more. Ninety-nine patients (25%) had a second operation, 92 (93%) at least in part for implant removal (12 for wire migration [3% of all fractures, 12% of reoperations]). We considered patient-related, fracture-related, and implant-related endpoints as possible factors associated with reoperation. With a total sample size of 99 reoperations, an ? of 0.05, and an effect size of 0.3, we had 87% power.ResultsReoperation was less common in men (36 [36%], women: 63 [64%]; adjusted odds ratio, 0.32; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). Similarly, request for implant removal was less in men (33 [36%], women: 59 [64%], adjusted odds ratio, 0.31; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001).ConclusionsPatients who have operative fixation of a fracture of the olecranon can be counseled that most patients keep their implants, that only 3% experience implant migration, and that technical factors such as the type or configuration of an implant seem less important than personal factors in determining who requests a second surgery for implant removal.Level of evidenceLevel III, prognostic study.

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Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.

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Healing of non-displaced fractures produced by fatigue loading of the mouse ulna.

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