A new family with epiphyseal chondrodysplasia type Miura.

Epiphyseal chondrodysplasia, Miura type (ECDM) is a skeletal dysplasia with tall stature and distinctive skeletal features caused by heterozygous NPR2 pathogenic variants. Only four families have been reported. We present a family with five affected individuals (mother, three sons, and daughter). The mother's phenotype was relatively mild: borderline tall stature and elongated halluces operated during childhood. The children were remarkably more severely affected with tall stature, scoliosis, and elongated toes and fingers leading to suspicion of Marfan syndrome. Progressive valgus deformities (at the hips, knees, and ankles) were the main complaints and necessitated orthopedic investigations and surgery. Radiographs showed coxa valga, scoliosis, multiple pseudoepiphyses of the fingers and toes with uneven elongation of the digits and ankle valgus. The two older brothers underwent osteotomies and guided growth for axial deformities and arthrodesis for elongated halluces. Genetic testing confirmed the clinical diagnosis of ECDM: all affected individuals had a heterozygous c.2647G>A (p.Val883Met) NPR2 variant in a highly conserved region in the carboxyl-terminal guanylyl cyclase domain. This two-generation family elucidates the clinical and radiological variability of the disease. These rare cases are important to gain further understanding of the fundamental processes of growth regulation.

Biallelic variants p.Arg1133Cys and p.Arg1379Cys in COL2A1: Further delineation of phenotypic spectrum of recessive Type 2 collagenopathies.

The phenotypic spectrum of Type 2 collagenopathies ranges from lethal achondrogenesis Type 2 to milder osteoarthritis with mild chondrodysplasia. All of them are monoallelic except for the two recent reports showing that biallelic variants in COL2A1 can cause spondyloepiphyseal dysplasia congenita in two children. Here we report two additional families with homozygous variants, c.4135C>T (p.Arg1379Cys) and c.3190C>T (p.Arg1133Cys) in COL2A1 resulting in two distinct skeletal dysplasia phenotypes of intermediate severity. Though all six patients from four families exhibit a spondylo-epimetaphyseal dysplasia, they demonstrate a wide variation in severity of short stature and involvement of epiphyses, metaphyses, and vertebrae. We hypothesize that the variants are likely to be hypomorphic, given the underlying mechanisms of disease causation for known heterozygous variants in COL2A1. With this report, we provide further evidence to the existence of autosomal recessive Type 2 collagenopathy.

Trevor's disease of the distal radioulnar joint in two children with achondroplasia.

Two children with achondroplasia who developed an abnormal bony outgrowth at the distal radioulnar joint (DRUJ), indistinguishable from an osteochondroma on histology, but the radiographic appearance, location, and asymmetry suggested the rare diagnosis of dysplasia epiphysealis hemimelica (DEH or "Trevor's disease"). One child experienced symptomatic relief with surgical excision and one was observed clinically due to lack of significant symptoms. These are the first presented cases of DEH in achondroplasia, both affecting the DRUJ. Due to the infrequency of DEH, more research is needed to better understand the potential connection to achondroplasia. For management, we suggest shared surgical decision making based on symptoms.

Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.

Acrodysostosis refers to a rare heterogeneous group of bone dysplasias that share skeletal features, hormone resistance, and intellectual disability. Two genes have been associated with acrodysostosis with or without hormone resistance (PRKAR1A and PDE4D). Severe intellectual disability has been reported with acrodysostosis but brain malformations and ichthyosis have not been reported in these syndromes. Here we describe a female patient with acrodysostosis, intellectual disability, cerebellar hypoplasia, and lamellar ichthyosis. The patient has an evolving distinctive facial phenotype and childhood onset ataxia. X-rays showed generalized osteopenia, shortening of middle and distal phalanges, and abnormal distal epiphysis of the ulna and radius. Brain magnetic resonance imaging showed cerebellar atrophy without other brainstem abnormalities. Genetic workup included nondiagnostic chromosomal microarray and skeletal dysplasia molecular panels. These clinical findings are different from any recognized form of acrodysostosis syndrome. Whole exome sequencing did not identify rare or predicted pathogenic variants in genes associated with known acrodysostosis, lamellar ichthyosis, and other overlapping disorders. A broader search for rare alleles absent in healthy population databases and controls identified two heterozygous truncating alleles in FBNL7 and PPM1M genes, and one missense allele in the NPEPPS gene. Identification of additional patients is required to delineate the mechanism of this unique disorder.

Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time.

Computed tomography and finite element modeling were used to assess bone structure at the knee as a function of time after spinal cord injury. Analyzed regions experienced degradation in stiffness, mineral density, and content. Changes were well described as an exponential decay over time, reaching a steady state 3.5 years after injury. INTRODUCTION: Spinal cord injury (SCI) is associated with bone fragility and an increased risk of fracture around the knee. The purpose of this study was to investigate bone stiffness and mineral content at the distal femur and proximal tibia, using finite element (FE) and computed tomography (CT) measures. A cross-sectional design was used to compare differences between non-ambulatory individuals with SCI as a function of time after injury (0-50 years). METHODS: CT scans of the knee were obtained from 101 individuals who experienced an SCI 30 days to 50 years prior to participation. Subject-specific FE models were used to estimate stiffness under axial compression and torsional loading, and CT data was analyzed to assess volumetric bone mineral density (vBMD) and bone mineral content (BMC) for integral, cortical, and trabecular compartments of the epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. RESULTS: Bone degradation was well described as an exponential decay over time (R2 = 0.33-0.83), reaching steady-state levels within 3.6 years of SCI. Individuals at a steady state had 40 to 85% lower FE-derived bone stiffness and robust decreases in CT mineral measures, compared to individuals who were recently injured (t ≤ 47 days). Temporal and spatial patterns of bone loss were similar between the distal femur and proximal tibia. CONCLUSIONS: After SCI, individuals experienced rapid and profound reductions in bone stiffness and bone mineral at the knee. FE models predicted similar reductions to axial and torsional stiffness, suggesting that both failure modes may be clinically relevant. Importantly, CT-derived measures of bone mineral alone underpredicted the impacts of SCI, compared to FE-derived measures of stiffness. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01225055, NCT02325414).

The effects of surgical treatment with chondroblastoma in children and adolescents in open epiphyseal plate of long bones.

BACKGROUND: Chondroblastoma is a rare benign cartilaginous tumor, which primarily occurs in children and adolescents. Chondroblastoma commonly originates in the epiphyseal plate of long bones. An aggressive curettage treatment is recommended to manage lesion, which may jeopardize an open epiphyseal plate and result in limb shortening and deformity as the limb grows and develops. The purpose is to observe surgical effects of chondroblastoma on open epiphyseal plate of long bones in children and adolescents and explore influences on limb growth and development. METHODS: We retrospectively reviewed 18 cases of long bone chondroblastoma with open epiphyseal growth plate during March 2004 to October 2010 in our center. Seven females and 11 males with mean age of 11.6 ± 2.0 years old (8-15 years) were included. Patients, who suffered from trauma and pathological fracture of the epiphyseal plate or congenital diseases such as poliomyelitis, congenital dementia, and cartilage malnutrition, were excluded. All patients were treated with meticulous intralesional curettage and inactivity with alcohol followed by bone grafts. All cases were followed up 8.2 ± 1.7 years (5-11.5 years). RESULTS: All had no local recurrence and distance metastasis. The length of the affected limb was short, 18.47 ± 7.22 mm (1.5-30 mm). There was no obvious relativity with tumor activity (P = 0.061). Meanwhile, there were obvious relativity with the greatest dimension of the lesion (TGD) (P = 0.003), the vertical dimension between edge of lesion and epiphyseal line (TVD) (P = 0.010), and area ratio of lesion to local epiphysis (lesion/growth plate) (P = 0.015). The MSTS93 (Revised Musculoskeletal Tumor Society Rating Scale 93) and SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey) had been significantly improved (P < 0.01). CONCLUSION: Managing of chondroblastoma located in open epiphyseal plate of a long bone with meticulous curettage, inactivity, and bone grafts can control tumor progression and recurrence effectively. Meanwhile, early detection and prompt surgical treatment intervention, which reduced significantly the tumor to influence limb growth and development, get encouraging limb function. TRIAL REGISTRATION: This is a retrospective study, which was not registered in any trial registry.

The Role of the Basement Plate in Physeal Bar Formation.

BACKGROUND: Physeal fractures and resultant physeal bars can pose significant problems in skeletal development for the injured growing child. Although now well-recognized, only a small body of experimental literature covering this problem is available. The goal of this study was to help further develop an understanding of the different regions of the physis and the way in which each region responds to injury/fracture. METHODS: This Institutional Animal Care and Use Committee (IACUC)-approved study assessed bar formation using radiologic and histologic methods and measured leg lengths of skeletally immature rats. The right tibia was used as the control to measure leg length discrepancy (LLD), and the left tibia received either a fracture only (F), an epiphyseal scrape (ES), an epiphyseal drilling procedure (ED), or metaphyseal drilling (MD). Radiographs and LLD measurements were obtained at postoperative days 0, 21, and 56. RESULTS: A significant LLD was present at day 56 in the ED group (P=0.01). Radiographic identification of bars showed significant evidence of bar formation for the ES and ED groups at 21 days and the ED group at 56 days (P<0.05). Histologic examination showed a high incidence of histologic physeal bar formation in the ES, ED, and MD groups at 21 and 56 days. CONCLUSIONS: Findings showed that the physis was able to continue to grow following an injury to the physis' hypertrophic region. MD produced little effects with few physeal bars and little LLD. By postoperative day 56, ED animals showed greater LLD than ES animals. Penetration of the basement plate was more likely to lead to bar formation/growth retardation than was ablation of the epiphyseal region of the physis (including resting cells). CLINICAL RELEVANCE: Data presented here provides insight into the importance of different regions of the physis and its repair/continued growth after physeal fracture. We suggest that a better understanding of the physiological cause of physeal arrest after physeal fracture will be important for the development of treatments to prevent physeal arrest or to treat physeal arrest after it occurs.

Restoration of Blood Flow to the Proximal Femoral Epiphysis in Unstable Slipped Capital Femoral Epiphysis by Modified Dunn Procedure: A Preliminary Angiographic and Intracranial Pressure Monitoring Study.

BACKGROUND: The major complication of unstable slipped capital femoral epiphysis (SCFE) is avascular necrosis (AVN) of the femoral head. The purpose of this study was to document by angiography the preoperative and postoperative perfusion to the proximal femoral epiphysis following an unstable SCFE. A specific aim was to determine whether blood flow could be restored. A secondary aim was to determine the efficacy of an intracranial pressure (ICP) monitor to assess blood flow within the femoral head intraoperatively. METHODS: Nine patients with an unstable SCFE underwent superselective angiogram of the medial circumflex femoral artery preoperatively, followed by operative fixation with an open reduction using a modified Dunn approach. Femoral head blood flow was evaluated with an ICP monitor. Angiography was repeated postoperatively. Patients were followed radiographically to assess for AVN. RESULTS: Follow-up averaged 22 months. Six patients did not have arterial flow to the femoral head on the preoperative angiogram. Flow was restored postoperatively on angiogram in 4 of the 6 patients. Two patients developed AVN. One had no flow to the femoral head preoperatively or postoperatively on angiogram and complete tearing of the periosteum was noted. In 1 patient, there was no ICP waveform after the initial reduction. After removing more callous and repeating reduction, the waveform returned. Of the 2 patients with AVN, 1 had an ICP waveform after reduction. CONCLUSIONS: This study documents that some patients with unstable SCFE present with reduced femoral head blood supply due to SCFE. It also demonstrates blood flow restoration in 4 patients by angiogram and 5 by ICP monitor after surgical treatment. No patient immediately lost blood flow due to surgery. ICP monitor is a safe intraoperative tool for real-time assessment of femoral head blood flow during open reduction of unstable SCFE. Presence of flow by ICP is not a guarantee that AVN will not develop, but absence of flow was predictive of AVN. LEVEL OF EVIDENCE: Therapeutic level I-prognostic. See Instructions for Authors for a complete description of levels of evidence.

Meagre effects of disuse on the human fibula are not explained by bone size or geometry.

Fibula response to disuse is unknown; we assessed fibula bone in spinal cord injury (SCI) patients and able-bodied counterparts. Group differences were smaller than in the neighbouring tibia which could not be explained by bone geometry. Differential adaptation of the shank bones may indicate previously unknown mechanoadaptive behaviours of bone. INTRODUCTION: The fibula supports only a small and highly variable proportion of shank compressive load (-8 to +19 %), and little is known about other kinds of stresses. Hence, whilst effects of habitual loading on tibia are well-known, fibula response to disuse is difficult to predict. METHODS: Therefore, we assessed fibular bone strength using peripheral quantitative computed tomography (pQCT) at 5 % increments from 5 to 90 % distal-proximal tibia length in nine participants with long-term spinal cord injury (SCI; age 39.2 ± 6.2 years, time since injury 17.8 ± 7.4 years), representing a cross-sectional model of long-term disuse and in nine able-bodied counterparts of similar age (39.6 ± 7.8 years), height and mass. RESULTS: There was no group difference in diaphyseal fibula total bone mineral content (BMC) (P = 0.22, 95 % CIs -7.4 % to -13.4 % and +10.9 % to +19.2 %). Site by group interactions (P < 0.001) revealed 27 and 22 % lower BMC in SCI at 5 and 90 % (epiphyseal) sites only. Cortical bone geometry differed at mid and distal diaphysis, with lower endocortical circumference and greater cortical thickness in SCI than able-bodied participants in this region only (interactions both P < 0.01). Tibia bone strength was also assessed; bone by group interactions showed smaller group differences in fibula than tibia for all bone parameters, with opposing effects on distal diaphysis geometry in the two bones (all Ps < 0.001). CONCLUSIONS: These results suggest that the structure of the fibula diaphysis is not heavily influenced by compressive loading, and only mid and distal diaphysis are influenced by bending and/or torsional loads. The fibula is less influenced by disuse than the tibia, which cannot satisfactorily be explained by differences in bone geometry or relative changes in habitual loading in disuse. Biomechanical study of the shank loading environment may give new information pertaining to factors influencing bone mechanoadaptation.

Surgical Techniques for Displaced Radial Neck Fractures: Predictive Factors of Functional Results.

BACKGROUND: Fractures of the radial neck represent about 1% of all childhood fractures and 5% to 10% of childhood traumatic lesions involving the elbow. Management of these fractures in children is still controversial. Intramedullary percutaneous nail reduction (Métaizeau technique) is considered the most effective surgical technique because of its excellent results and easy learning curve. Complications may arise, however, especially in Böhler technique, in which a percutaneous pin is placed over the radial head. When this technique does not provide correct reduction, open reduction must be performed. Because open reduction is traditionally associated with a high risk of complications, however, its use is restricted to severely displaced fractures and only when the percutaneous techniques have failed or their application contraindicated because of associated injuries to the distal radius. METHODS: In this retrospective study, we evaluated 51 children between the ages of 6 and 15 years who presented to our institution from 1996 to 2012 with Métaizeau-modified Judet grades 3, 4a, and 4b radial head fractures. The surgical techniques used were closed reduction and casting under general anesthesia (n=7), closed reduction and intramedullary nailing using Métaizeau technique (n=27), and Métaizeau technique and open reduction with intramedullary nailing (n=17). Functional results of the 3 surgical techniques were evaluated using the Mayo Elbow Performance Score (MEPS) and compared by modified Judet classification using χ analysis. RESULTS: No statistic significant association was found between type of surgery and final MEPS was observed (P=0.110). However, a significant association was found between initial modified Judet grade and final MEPS. CONCLUSIONS: In the present study, final functional outcome seems to be not affected by open reduction but was significantly associated with initial modified Judet grade. LEVEL OF EVIDENCE: Level III-retrospective study comparing closed and open reduction techniques, performed at the same institution.

Subchondral and epiphyseal bone remodeling following surgical transection and noninvasive rupture of the anterior cruciate ligament as models of post-traumatic osteoarthritis.

OBJECTIVE: Animal models are frequently used to study post-traumatic osteoarthritis (PTOA). A common anterior cruciate ligament (ACL) injury model is surgical transection, which may introduce confounding factors from surgery. Noninvasive models could model human injury more closely. The purpose of this study was to compare subchondral and epiphyseal trabecular bone remodeling after surgical transection and noninvasive rupture of the ACL. METHODS: Thirty-six rats were randomized to an uninjured control, surgical transection (Transection), or noninvasive rupture (Rupture). Animals were randomized to 4 or 10 week time points (n = 6 per group). Micro computed tomography (µCT) imaging was performed with an isotropic voxel size of 12 µm. Subchondral and epiphyseal bone was segmented semi-automatically, and morphometric analysis was performed. RESULTS: Transection caused a greater decrease in subchondral bone volume fraction (BV/TV) than Rupture in the femur and tibia. Rupture had greater subchondral bone tissue mineral density (TMD) at 4 and 10 weeks in the femur and tibia. Subchondral bone thickness (SCB.Th) was decreased in the femur in Transection only. Epiphyseal BV/TV was decreased in Transection only, and Rupture exhibited increased femoral epiphyseal TMD compared to both Control and Transection. Rupture exhibited greater femoral epiphyseal trabecular thickness (Tb.Th.) compared to Control and Transection at 4 weeks, and both Rupture and Transection had increased femoral epiphyseal Tb.Th. at 10 weeks. Epiphyseal trabecular number (Tb.N) was decreased in both injury groups at both time points. Femoral and tibial epiphyseal structure model index (SMI) increased in both groups. CONCLUSIONS: The two injury models cause differences in post-injury bone morphometry, and surgical transection may be introducing confounding factors that affect downstream bony remodeling.

A Structural and Mechanism-Based Perspective Toward Understanding Pediatric and Adult Sports Injuries.

OBJECTIVE: The purpose of this article is to compare the injury patterns in skeletally mature patients versus skeletally immature patients to better understand the factors that cause the specific injury appearance. The physis as the essential factor in the injury manifestation will be examined. CONCLUSION: The physis and immature chondroosseous junctions operate as the weak links in the immature skeleton and are the deciding factors in the pattern of injury, even though the injury mechanisms are identical to those in adults.

Internal Fixation With Absorbable Rods for the Treatment of Displaced Radial Neck Fractures in Children.

BACKGROUND: The treatment of radial neck fractures with complete displacement or severe displacement and an angle of >30 degrees is controversial. The currently used methods, including the Metaizeau technique, are associated with drawbacks such as imperfect reduction, epiphyseal damage, and delayed functional recovery. To overcome these drawbacks, we used absorbable rod fixation followed by early functional training for the treatment of displaced radial neck fractures in children. METHODS: In this study, 68 patients (age, 4 to 12 y; average, 8.4 y; average angle, 58 degrees; average displacement, 53%) with radial neck fractures with Salter-Harris grades II to IV underwent lateral elbow open reduction and absorbable rod fixation. At 3 weeks postoperatively, the patients' plaster casts were removed, and functional training was started. RESULTS: Anatomic reduction was achieved in all patients. We followed-up 68 patients for 6 months to 4 years (average, 41 mo). No cases of radial nerve injury, radial bone necrosis, myositis ossificans, and postoperative infection were observed. The functional recovery was "excellent" in 43 patients, "good" in 13 patients, "average" in 12 patients, and "bad" in 0 patients, according to the Morrey evaluation standard. CONCLUSION: Open reduction with absorbable rod fixation for the treatment of displaced radial neck fractures in children was feasible and was a choice in children. LEVEL OF EVIDENCE: Therapeutic II.

Influence of chronic stroke impairments on bone strength index of the tibial distal epiphysis and diaphysis.

SUMMARY: The influence of various stroke impairments on bone health is poorly understood. This study showed that muscle function and small artery compliance were more strongly associated with the bone strength index at the tibial diaphyseal and epiphyseal regions, respectively. These impairments should be targeted in promoting bone health post-stroke. INTRODUCTION: This study examined the bone structural properties of the tibial distal epiphysis and diaphysis after chronic stroke and identified the clinical correlates of the bone strength index measured at these sites. METHODS: The tibial distal epiphysis (4% site) and diaphysis (66% site) were scanned on both sides in 66 chronic stroke patients and 23 control participants using peripheral quantitative computed tomography. Dynamic knee muscle strength, balance function, spasticity, arterial compliance, and endurance were also measured in the stroke group. RESULTS: At the 4% site, multivariate analysis showed a significant side×group interaction effect (Wilk's lambda=3.977, p<0.001), with significant side-to-side differences in total volumetric bone mineral density (vBMD), trabecular vBMD, and bone strength index in the stroke group, but not in the control group. A significant side×group interaction was also found at the 66% site (Wilk's lambda=4.464, p<0.001), with significant side-to-side differences in cortical vBMD, cortical area, cortical thickness, and bone strength index in the stroke group only. Balance and endurance were independently associated with bone strength index at both tibial sites in the paretic leg (p<0.05) after adjusting for relevant factors in multivariate regression analysis. Small artery compliance and muscle strength were significantly associated with the bone strength index at the 4% site and 66% site, respectively. CONCLUSIONS: The influence of various stroke impairments on bone was region-specific. While muscle function was more strongly associated with the bone strength index in the diaphyseal region, the effect of vascular health was more apparent in the tibial epiphysis in the paretic leg.

Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases.

BACKGROUND: Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple bone dysplasia, hepatic dysfunction, and growth retardation. All clinical manifestations result from gene mutations encoding pancreatic endoplasmic reticulum eIF2 α kinase (PERK), an endoplasmic reticulum transmembrane protein that plays a role in the unfolded protein response. Histological and ultrastructural lesions of bone and pancreas have been described in animal models and WRS patients. However, histological and ultrastructural findings of other organs, especially of the liver, are lacking. METHODS: Autopsy specimens from two pediatric patients with WRS were analyzed. An immunohistochemical study was performed on the pancreas. An ultrastructural study was realized from samples of liver, pancreas, kidney, and myocardium. Our findings were compared with those of the literature and correlated with the molecular data. RESULTS: Hepatocytes and pancreatic exocrine cells exhibited very peculiar features of necrosis suggestive of secondary changes because of endoplasmic reticulum overload. Steatosis occurred in renal tubular cells, hepatocytes, and myocardial fibers. Abnormal mitochondria were noted in renal and myocardial fibers. Pancreas islets were characterized by a marked reduction in the number of insulin-secreting ß cells. CONCLUSIONS: The histological and ultrastructural features that occur in WRS are directly or indirectly linked to endoplasmic reticulum (ER) dysfunction and can explain the peculiar phenotype of this syndrome.

Survival, recurrence, and function after epiphyseal preservation and allograft reconstruction in osteosarcoma of the knee.

BACKGROUND: Bone tumor resections for limb salvage have become the standard treatment. Recently, intercalary tumor resection with epiphyseal sparing has been used as an alternative in patients with osteosarcoma. The procedure maintains normal joint function and obviates some complications associated with osteoarticular allografts or endoprostheses; however, long-term studies analyzing oncologic outcomes are scarce, and to our knowledge, the concern that a higher local recurrence rate may be an issue has not been addressed. QUESTIONS/PURPOSES: We wanted to assess (1) the overall survival in patients treated with this surgical technique; (2) the percentage of local recurrence and limb survival, specifically the incidence of recurrence in the remaining epiphysis; (3) the frequency of orthopaedic complications, and, (4) the functional outcomes in patients who have undergone intercalary tumor resection. METHODS: We analyzed all 35 patients with osteosarcomas about the knee (distal femur and proximal tibia) treated at our center between 1991 and 2008 who had resection preserving the epiphysis and reconstruction with intercalary allografts. Minimum followup was 5 years, unless death occurred earlier (mean, 9 years; range, 1-16 years), and no patients were lost to followup. During the study period, our indications for this approach included patients without metastases, with clinical and imaging response to neoadjuvant chemotherapy, that a residual epiphysis of at least 1 cm thickness could be available after a surgical margin width in bone of 10 mm was planned, and 16% of patients (35 of 223) meeting these indications were treated using this approach. Using a chart review, we ascertained overall survival of patients, oncologic complications such as local recurrence and tumor progression, limb survival, and orthopaedic complications including infection, fracture, and nonunion. Survival rates were estimated using the Kaplan-Meier method. Patient function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system. RESULTS: Overall survival rate of the patients was 86% (95% CI, 73%-99%) at 5 and 10 years. Five patients died of disease. No patient had a local recurrence in the remaining bony epiphysis, but three patients (9%; 95% CI, 0%-19%) had local recurrence in the soft tissue. The limb survival rate was 97% (95% CI, 89%-100%) at 5 and 10 years. Complications treated with additional surgical procedures were recorded for 19 patients (54%), including three local recurrences, two infections, 11 fractures, and three nonunions. In 10 of these 19 patients, the allograft was removed. Only five of the total 35 study patients (14%) lost the originally preserved epiphysis owing to complications. The mean functional score was 26 points (range, 10-30 points, with a higher score representing a better result) at final followup. CONCLUSIONS: Although the recurrence rate was high in this series, the small sample size means that even one or two fewer recurrences might have resulted in a much more favorable percentage. Because of this, future, larger studies will need to determine whether this is a safe approach, and perhaps should compare epiphyseal preservation with other possible approaches, including endoprosthetic reconstruction and/or osteoarticular allografts. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Low magnitude high frequency vibration accelerated cartilage degeneration but improved epiphyseal bone formation in anterior cruciate ligament transect induced osteoarthritis rat model.

OBJECTIVES: To evaluate the effects of low-magnitude high-frequency vibration (LMHFV) on degenerated articular cartilage and subchondral bone in anterior cruciate ligament transection (ACLT) induced osteoarthritis (OA) rat model. METHODS: 6 months old female Sprague-Dawley rats received ACLT on right knee and randomly divided into treatment and control groups. OA developed 12 weeks after surgery. LMHFV (35 Hz, 0.3 g) treatment was given 20 min/day and 5 days/week. After 6, 12 and 18 weeks, six rats of each group were sacrificed at each time point and the right knees were harvested. OA grading score, distal femur cartilage volume (CV), subchondral bone morphology, elastic modulus of cartilage and functional changes between groups were analyzed. RESULTS: Increased cartilage degradation (higher OA grading score) and worse functional results (lower duty cycle, regular index and higher limb idleness index) were observed after LMHFV treatment (P = 0.011, 0.020, 0.012 and 0.005, respectively). CV increased after LMHFV treatment (P = 0.019). Subchondral bone density increased with OA progress (P < 0.01). Increased BV/TV, Tb.N and decreased Tb.Sp were observed in distal femur epiphysis in LMHFV treatment group (P = 0.006, 0.018 and 0.011, respectively). CONCLUSION: LMHFV accelerated cartilage degeneration and caused further functional deterioration of OA affected limb in ACLT-induced OA rat model. In contrast, LMHFV promoted bone formation in OA affected distal femur epiphysis, but did not reverse OA progression.

Bone mineral and stiffness loss at the distal femur and proximal tibia in acute spinal cord injury.

SUMMARY: Computed tomography and finite element modeling were used to assess bone mineral and stiffness loss at the knee following acute spinal cord injury (SCI). Marked bone mineral loss was observed from a combination of trabecular and endocortical resorption. Reductions in stiffness were 2-fold greater than reductions in integral bone mineral. INTRODUCTION: SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. The large majority of these fractures occur around regions of the knee. Our purpose was to quantify changes to bone mineral, geometry, strength indices, and stiffness at the distal femur and proximal tibia in acute SCI. METHODS: Quantitative computed tomography (QCT) and patient-specific finite element analysis were performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range 2.6-4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. Changes in bone volumes, cross-sectional areas, strength indices and stiffness were also determined. RESULTS: Bone mineral loss was similar in magnitude at the distal femur and proximal tibia. Reductions were most pronounced at epiphyseal regions, ranging from 3.0 % to 3.6 % per month for integral BMC (p < 0.001) and from 2.8 % to 3.4 % per month (p < 0.001) for integral vBMC. Trabecular BMC decreased by 3.1-4.4 %/month (p < 0.001) and trabecular vBMD by 2.7-4.7 %/month (p < 0.001). A 3.8-5.4 %/month reduction was observed for cortical BMC (p < 0.001); the reduction in cortical vBMD was noticeably lower (0.6-0.8 %/month; p ≤ 0.01). The cortical bone loss occurred primarily through endosteal resorption, and reductions in strength indices and stiffness were some 2-fold greater than reductions in integral bone mineral. CONCLUSIONS: These findings highlight the need for therapeutic interventions targeting both trabecular and endocortical bone mineral preservation in acute SCI.

EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome.

OBJECTIVE: This study describes the clinical and genetic evaluation of permanent neonatal diabetes due to Wolcott-Rallison syndrome (WRS) in south Indian consanguineous families. We aimed to evaluate the genetic basis of the disease in eight children with WRS from five South Indian families. PATIENTS AND METHODS: We studied eight children who presented with permanent neonatal diabetes from five South Indian families. Follow up clinical evaluation revealed features (like liver disease, skeletal dysplasia, and thyroid dysfunction) suggestive of WRS. All the coding exons along with splice sites of KCNJ11, ABCC8, INS, GCK and EIF2AK3 genes were sequenced in all the probands. RESULTS: Two novel homozygous mutations (Trp658Ser, c.3150+1G>T) and one known homozygous mutation (Arg1065*, c.3193C>T) in EIF2AK3 gene were identified in children with WRS. Mutation Arg1065*was identified in four children. CONCLUSIONS: Our results in these families show that the mutations in homozygous state are likely to be causative. We suggest the screening for EIF2AK3 gene mutations as WRS is now recognized as the most frequent cause of neonatal diabetes in children with consanguineous parents. As the mode of inheritance is recessive, screening for genetic mutations becomes important to aid in risk prediction and clinical management.

Physeal arrest of the distal radius.

Fractures of the distal radius are among the most common pediatric fractures. Although most of these fractures heal without complication, some result in partial or complete physeal arrest. The risk of physeal arrest can be reduced by avoiding known risk factors during fracture management, including multiple attempts at fracture reduction. Athletes may place substantial compressive and shear forces across the distal radial physes, making them prone to growth arrest. Timely recognition of physeal arrest can allow for more predictable procedures to be performed, such as distal ulnar epiphysiodesis. In cases of partial arrest, physeal bar excision with interposition grafting can be performed. Once ulnar abutment is present, more invasive procedures may be required, including ulnar shortening osteotomy or radial lengthening.