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Concept: Bone fracture

481

To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures.

Concepts: Osteoporosis, Bone, Bone fracture, Fracture, Calcium

174

Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F-actin) bundles, appears to be important in human bone health, on the basis of pathogenic variants in PLS3 in five families with X-linked osteoporosis and osteoporotic fractures that we report here. The bone-regulatory properties of PLS3 were supported by in vivo analyses in zebrafish. Furthermore, in an additional five families (described in less detail) referred for diagnosis or ruling out of osteogenesis imperfecta type I, a rare variant (rs140121121) in PLS3 was found. This variant was also associated with a risk of fracture among elderly heterozygous women that was two times as high as that among noncarriers, which indicates that genetic variation in PLS3 is a novel etiologic factor involved in common, multifactorial osteoporosis.

Concepts: Osteoporosis, Bone, Genetics, Natural selection, Bone fracture, Fracture, Actin, Osteogenesis imperfecta

171

BACKGROUND: Children’s fractures have been enlisted among orthopaedics complaints of childhood obesity. Unhealthy lifestyle behaviours may contribute to increased risk. This study described the prevalence of overweight/obesity in children and adolescents reporting a recent fracture in relation to gender, dynamic of trauma, and site of fracture. METHODS: Four-hundred-forty-nine children and adolescents with fracture and 130 fracture-free controls were recruited from a large children’s hospital. The interaction between overweight and gender, dynamic of trauma, site of fracture was explored. Sports participation, television viewing, and calcium intake were also investigated. RESULTS: Overweight/obesity rate was increased in girls with fracture either at the upper or the lower limb (p= 0.004), while it was increased only in boys with fracture at the lower limb (p <0.02). Overweight/obesity rate did not differ between groups with low or moderate trauma. TV viewing [greater than or equal to] 2 hrs was more frequent in children with fractures than controls (61.5% vs 34.5%, p =0.015) in the overweight/obese group. CONCLUSIONS: The increased prevalence of overweight/obesity in children with fractures is related to gender and site of fracture. Higher levels of sedentary behaviours characterize overweight children reporting fractures.

Concepts: Bone, Epidemiology, Nutrition, Bone fracture, Obesity, Childhood, Orthopedic surgery, Case-control study

170

BACKGROUND: The most common mechanical failure in the internal fixation of trochanteric hip fractures is the cut-out of the sliding screw through the femoral head. Several factors that influence this complication have been suggested, but there is no consensus as to the relative importance of each factor.The purpose of this study was to analyse the cut-out complication with respect to the following variables: patients` age, fracture type, fracture reduction, implant positioning and implant design. METHODS: 3066 consecutive patients were treated for trochanteric fractures with Gamma Nails between 1990 and 2002 at the Centre de Traumatologie et de l`Orthopedie (CTO), Strasbourg, France. Cut-out complications were identified by reviewing all available case notes and radiographs. Subsequently, the data were analysed by a single reviewer (AJB) with focus on the studied factors. RESULTS: Seventy-one cut-out complications were found (2.3%) of the 3066 trochanteric fractures. Cut-out failure associated with avascular head necrosis, pathologic fracture, deep infection or secondary to prior failure of other implants were excluded from the study (14 cases). The remaining 57 cases (1.85 %, median age 82.6, 79% females) were believed to have a biomechanical explanation for the cut-out failure. 41 patients had a basicervical or complex fracture type. A majority of cut-outs (43 hips, 75%) had a combination of the critical factors studied; non-anatomical reduction, non-optimal lag screw position and the characteristic fracture pattern found. CONCLUSIONS: The primary cut-out rate of 1.85% was low compared with the literature. A typical cut-out complication in our study is represented by an unstable fracture involving the trochanteric and cervical regions or the combination of both, non-anatomical reduction and non-optimal screw position. Surgeons confronted with proximal femoral fractures should carefully scrutinize preoperative radiographs to assess the primary fracture geometry and fracture classification. To reduce the risk of a cut-out it is important to achieve both anatomical reduction and optimal lag screw position as these are the only two factors that can be controlled by the surgeon.

Concepts: Osteoporosis, Bone fracture, Hip fracture, Hip replacement, Orthopedic surgery, Avascular necrosis, Cultural studies, Bone fractures

169

To assess the relationship between surgical delay and mortality in elderly patients with hip fracture. Systematic review and meta-analysis of retrospective and prospective studies published from 1948 to 2011. Medline (from 1948), Embase (from 1974) and CINAHL (from 1982), and the Cochrane Library. Odds ratios (OR) and 95% confidence intervals for each study were extracted and pooled with a random effects model. Heterogeneity, publication bias, Bayesian analysis, and meta-regression analyses were done. Criteria for inclusion were retro- and prospective elderly population studies, patients with operated hip fractures, indication of timing of surgery and survival status.

Concepts: Osteoporosis, Bone fracture, Hip fracture, Evidence-based medicine, Systematic review, Cochrane Library, MEDLINE, Statistical inference

168

Background: The purpose of this study was to compare the biomechanical properties of locked versus nonlocked lateral fibular bridge plating of comminuted, unstable ankle fractures in a mode of catastrophic failure. Methods: We created comminuted Weber C fractures in 8 paired limbs from fresh cadavers. Fractures were plated with either standard or locked one-third tubular bridge plating techniques. Specimens were biomechanically evaluated by external rotation to failure while subjected to a compressive load approximating body weight. We measured the angle to failure, torque to failure, energy to failure and construct stiffness. Results: There was no significant difference in construct stiffness or other biomechanical properties between locked and standard one-third tubular plating techniques. Conclusion: We found no difference in biomechanical properties between locked and standard bridge plating of a comminuted Weber C fibular fracture in a model of catastrophic failure. It is likely that augmentation of fixation with K-wires or transtibial screws provides a construct superior to locked bridge plating alone. Further biomechanical and clinical analysis is required to improve understanding of the role of locked plating in ankle fractures and in osteoporotic bone.

Concepts: Osteoporosis, Bone, Bone fracture, Fracture, Elasticity, Forensic engineering, Plating, Fibula

167

BACKGROUND: Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OH)D3 (Vitamin D) as well as PTH (Parathyroid Hormone) the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. METHODS: In the presented study, we analyse the time course of 25(OH)D3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OH)D3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value <= 0.05 was considered significant. RESULTS: Serum levels of 25(OH)D3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. CONCLUSIONS: The time course of 25(OH)D3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for therapy and the monitoring of fracture healing.

Concepts: Osteoporosis, Bone, Vitamin D, Calcitonin, Bone fracture, Parathyroid hormone, Calcium, Hyperparathyroidism

150

Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from ‘within.’ Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay in vivo. The challenges still to be met are to determine whether measurement of porosity identifies persons at risk for fracture, whether this approach is compliments information obtained using bone densitometry, and whether changes in cortical porosity and other microstructural traits have the sensitivity to serve as surrogates of treatment success or failure.

Concepts: Osteoporosis, Bone, Bone fracture, Fracture, Skeletal system, Osseous tissue, Cortical bone, Cancellous bone

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Background The management of open fractures requires wound irrigation and d├ębridement to remove contaminants, but the effectiveness of various pressures and solutions for irrigation remains controversial. We investigated the effects of castile soap versus normal saline irrigation delivered by means of high, low, or very low irrigation pressure. Methods In this study with a 2-by-3 factorial design, conducted at 41 clinical centers, we randomly assigned patients who had an open fracture of an extremity to undergo irrigation with one of three irrigation pressures (high pressure [>20 psi], low pressure [5 to 10 psi], or very low pressure [1 to 2 psi]) and one of two irrigation solutions (castile soap or normal saline). The primary end point was reoperation within 12 months after the index surgery for promotion of wound or bone healing or treatment of a wound infection. Results A total of 2551 patients underwent randomization, of whom 2447 were deemed eligible and included in the final analyses. Reoperation occurred in 109 of 826 patients (13.2%) in the high-pressure group, 103 of 809 (12.7%) in the low-pressure group, and 111 of 812 (13.7%) in the very-low-pressure group. Hazard ratios for the three pairwise comparisons were as follows: for low versus high pressure, 0.92 (95% confidence interval [CI], 0.70 to 1.20; P=0.53), for high versus very low pressure, 1.02 (95% CI, 0.78 to 1.33; P=0.89), and for low versus very low pressure, 0.93 (95% CI, 0.71 to 1.23; P=0.62). Reoperation occurred in 182 of 1229 patients (14.8%) in the soap group and in 141 of 1218 (11.6%) in the saline group (hazard ratio, 1.32, 95% CI, 1.06 to 1.66; P=0.01). Conclusions The rates of reoperation were similar regardless of irrigation pressure, a finding that indicates that very low pressure is an acceptable, low-cost alternative for the irrigation of open fractures. The reoperation rate was higher in the soap group than in the saline group. (Funded by the Canadian Institutes of Health Research and others; FLOW ClinicalTrials.gov number, NCT00788398 .).

Concepts: Bone fracture, Infection, Wound, Lactated Ringer's solution, Soap, Nasal irrigation, Weather map, Castile soap

67

Background Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. Methods We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. Results At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P=0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. Conclusions In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834 .).

Concepts: Osteoporosis, Pharmacology, Bone, Clinical trial, Bone fracture, Hip fracture, Fracture, Placebo