Avascular Necrosis In Children Research Articles

Vitamin D Deficiency and Avascular Necrosis in Patients with Sickle Cell Disease: A Retrospective Cohort Study

Introduction Sickle cell disease (SCD) is an inherited hemoglobinopathy with complex systemic involvement. Avascular necrosis (AVN) is a devastating complication among patients with SCD. Vitamin D deficiency (VDD) is commonly found in SCD patients, but there is limited research on the potential role of VDD as a risk factor for AVN in SCD patients. This study aimed to assess the association between VDD and AVN and determine the patterns, risk factors, diagnosis, and treatment of AVN in SCD patients. Methods We conducted a retrospective cohort study of consecutive SCD patients diagnosed with VDD from January 2020 to December 2022 at Prince Sultan Medical Military City (PSMMC) in Riyadh, Saudi Arabia. Patients meeting the following criteria were included: (1) adults and children with confirmed SCD through hemoglobin electrophoresis and (2) tested for VDD. Patients who underwent bone marrow transplant were excluded. The main outcome measured was the occurrence of AVN. VDD was diagnosed in patients with 25-hydroxyvitamin D levels below 30 nmol/L. Magnetic resonance imaging was used to stage and confirm AVN diagnosis. Associations were assessed using the chi-square test, and logistic regression was performed to control for confounding. Results The study included 711 eligible SCD patients, with 271 (38%) being children. VDD affected 301 out of 711 patients (42.3%). Among these, 212 (70.4%) were adults (>18 years old). VDD was observed in 32.2% of children and 48.1% of adults. Of the total cohort, 127 (17.9%) patients experienced AVN, including 18 children. Among patients with VDD, 89 developed AVN, while VDD affected 212 patients without AVN. The time between VDD diagnosis and AVN presentation ranged from 3 to 12 months. Male patients accounted for 52% of AVN cases. The average age at AVN diagnosis was 30.9 ± 11 years. The most common clinical presentation of AVN was chronic joint pain in over 95% of patients. Other presentations included limping in 3.9% of patients and limited joint movement in one patient. Affected joints included the hip (86%), shoulder (16.5%), knee (4.7%), and sacroiliac joint (0.7%). Bilateral joint involvement was present in 50.4% of AVN patients. The majority of patients (76.4%) were diagnosed with advanced stage AVN (III/IV). Treatment of patients with AVN included joint replacement in 44 (34.6%) patients, while the remaining 83 patients managed with conservative therapy such as pain control and physiotherapy. Patients with a history of VDD were significantly associated with a higher risk of AVN (p < 0.001), as seen in Table 1. Multivariate logistic regression showed SCD patients with VDD had 9.79 times the odds of AVN compared to SCD patients without VDD (OR 9.79; 95% CI: 5.25-18.26). Other statistically significant risk factors for AVN included frequent vaso-occlusive crises (three or more episodes per year), older age, history of acute chest syndrome, and low hemoglobin F levels. Conclusion AVN is a significant cause of morbidity in our SCD cohort, with most patients having advanced AVN disease. VDD is an independent risk factor for AVN in patients with SCD. Well-designed randomized trials are needed to determine the effect of vitamin D supplementation in reducing AVN in children and adults with SCD.

Pathological fracture increases the risk of unsatisfactory functional results and avascular necrosis in children with proximal femur simple bone cysts

IntroductionProximal femur simple bone cysts (SBCs) are rare in children, but with a risk of pathological fractures and the associated poor outcomes. This study aimed to evaluate the functional and radiographic outcomes of children with proximal femur SBCs. Patients and Methods38 children with proximal femur SBCs treated surgically at our department, West China hospital, were enrolled in the study. Patients were divided into two groups according to whether pathological fractures presented before treatment. The non-fracture group received treatment of open curettage, cavity electrocauterization, bone grafting, and fixation (proximal femoral plate, intramedullary nail or Kirschner wire). The pathological fracture group received the same procedures of curettage, electrocauterization, grafting, and fixation. Autogenous iliac bone grafting was done in all cases, and the artificial bone was used as a supplementary based on the size of the cavity. Postoperatively, all patients underwent hip spica or similar orthosis immobilization for six weeks and received the same rehabilitation program after the removal of hip spica. Patients were evaluated by two independent observers, including the functional results based on the Ratliff's criteria, avascular necrosis, healing rate based on the Neer scoring system, coxa vara, and premature physeal arrest. We described the good outcome in Ratliff's criteria as “Satisfactory results”, and fair and poor outcomes as “Unsatisfactory results.” Grade 1 and grade 2 Neer results were termed as failures in treatment, and grades 3 and 4 were considered successes and healing. Results38 patients with 38 hips (18 on the left side and 20 on the right side) were evaluated, including 9 females and 29 males, with a mean age of 9.0±2.6 years old (range, 5 to 14 years). There was no significant difference between these two groups in the baseline data of gender, age, side, grafting, staging, and fixation methods. The rate of unsatisfactory functional results in the pathological fractures group was 56.3% (9/16), significantly higher than that in patients without fracture (22.7%, 5/22. p= 0.047). There was also a significant difference in avascular necrosis of the femoral head between the pathological fractures group (7/16) and the group without fracture (2/22, p=0.021). Thirty cases presented with healing, including 13 in the fractures group and 17 in the non-fracture group (p=1.000), and eight cases were graded as failures (2 cases of grade 1 and 6 cases of grade 2). There were also no significant differences between these two groups in premature physeal arrest (2 in fracture group and 1 in non-fracture group, P=0.562), and Coxa vara (3 in the fracture group and 0 in non-fracture group, P=0.066). ConclusionsPathological fracture significantly increases the risk of unsatisfactory functional results and avascular necrosis of the femoral head in patients with femoral neck SBCs. Prophylactic treatment and fixation of SBCs in weight bearing proximal femur region is better to manage without complications than managing with pathological fractures.

Risk factors related with avascular necrosis after internal fixation of femoral neck fractures in children: a systematic review and meta-analysis.

Less than 1% of children develop femoral neck fractures (FNF), making them uncommon. However, they may have dangerous side effects, like avascular necrosis. Even though several risk factors for postoperative avascular necrosis have been identified, there is still debate regarding them. In this investigation, a meta-analysis was performed to examine the potential causes of postoperative avascular necrosis in children with FNF. We conducted a thorough literature search to find risk factors for avascular necrosis (AVN) after internal fixation of pediatric FNF. Until December 2022, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Orthosearch, and Sinomed. Software Zotero 6.0 and Stata 17.0 were used to organise and synthesise the data. Finally, a sensitivity and publication bias test was carried out. Our study includes a total of 15 case-control studies involving 814 patients. The risk of postoperative AVN increased with age at fracture encounter (95% CI: 0.64-1.88, P = 0.0003), initial fracture displacement (95% CI: 1.87-9.54, P = 0.0005), and poor fracture reduction (95% CI:1.95-22.34, P = 0.0024) were risk factors for postoperative AVN. There was no significant relationship between gender and postoperative AVN (95% CI: 0.52-1.31, P = 0.41). Conversely, Postoperative AVN and reduction methods have no connection with each other (95% CI: 0.77-2.66, P = 0.25), procedure time (95% CI: 0.43-2.99, P = 0.16), or injury mechanism (95% CI: 0.32-2.26, P = 0.75). The incidence of post-operative AVN varies between Delbet fracture types (95% CI: 0.15-0.31, P < 0.0001), with the overall trend being that the incidence of post-operative AVN is highest for type II, lowest for type IV, and close for types I and III, but it is not clear which type of fracture is the independent risk factor. Funnel plots indicate no significant publication bias. In line with this study, About 26% of children who underwent surgery for a femoral neck fracture suffered postoperative AVN. The main risk factors for AVN were the child's age, the initial displacement of the fractures, and poorly reduced fractures. The risk of AVN did not significantly correlate with gender, the time of the procedure, reduction methods or the mechanism of injury. The overall trend in the incidence of postoperative AVN for the different Delbet types of fracture is that the incidence of postoperative AVN is highest for type II, lowest for type IV, and close for types I and III, but it is not clear which type of fracture is the independent risk factor.

The incidence of avascular necrosis in children with cerebral palsy after hip containment surgery.

To establish the rate of avascular necrosis after hip reconstruction surgery in children with cerebral palsy and to identify risk factors that influence the development of avascular necrosis in this population. An institutional review board-approved retrospective review was conducted on children with cerebral palsy who underwent hip containment surgery at a single institution. Radiographs were evaluated at three time points. The Reimer's migration percentage, neck shaft angle, epiphyseal shaft angle, acetabular index, center edge angle, and acetabular angle were measured. The presence of avascular necrosis was evaluated and graded by the Bucholz/Ogden and the Kalamchi/MacEwen classification systems. Multivariate logistic regression was performed to identify risk factors associated with the development of avascular necrosis. A total of 154 children with cerebral palsy underwent hip containment surgery on 223 hips. Twenty-nine children (18.8%) underwent both pelvic and femoral procedures; 36 children (23.4%) had only femoral procedures; 47 children (30.5%) had femoral and soft tissue; and 42 children (27.3%) had pelvic, femoral, and soft tissue procedures. Using the Bucholz and Ogden or the Kalamchi classifications, the rate of avascular necrosis was 24.7% (38/154). Of the variables evaluated, preoperative Reimers was found to be significant predictors of avascular necrosis. The rate of avascular necrosis was 26.7% for Gross Motor Functional Classification System level III, 24.1% for Gross Motor Functional Classification System level IV, and 27.3% for Gross Motor Functional Classification System level V. The overall rate of avascular necrosis in children undergoing hip containment surgery was 26.7%. Together, age at surgery, open reduction, previous surgery, preoperative Reimers, and estimated blood loss contributed to the development of postoperative avascular necrosis; however, only preoperative Reimers significantly contributed to the development of avascular necrosis in children with cerebral palsy undergoing hip containment procedures.

Prevalence of and Associations With Avascular Necrosis After Pediatric Sepsis: A Single-Center Retrospective Study.

Avascular necrosis (AVN) is a rare, but serious, complication after sepsis in adults. We sought to determine if sepsis is associated with postillness diagnosis of AVN, as well as potential-associated risk factors for AVN in children with sepsis. Retrospective observational study. Single academic children's hospital. Patients less than 18 years treated for sepsis or suspected bacterial infection from 2011 to 2017. Patients who developed AVN within 3 years after sepsis were compared with patients who developed AVN after suspected bacterial infection and with patients with sepsis who did not develop AVN. None. AVN was determined using International Classification of Diseases, 9th Edition/10th Edition codes and confirmed by chart review. The prevalence of AVN after sepsis was 0.73% (21/2,883) and after suspected bacterial infection was 0.43% (53/12,276; risk difference, 0.30; 95% CI, 0.0-0.63; p = 0.05). Compared with 43 sepsis controls without AVN, AVN in the 21 sepsis cases was associated with being older, having sickle cell disease and malignancy, higher body mass index, unknown source of infection, and low platelet count in the first 7 days of sepsis. Half of sepsis patients were treated with corticosteroids, and higher median cumulative dose of steroids was associated with AVN (23.2 vs 5.4 mg/kg; p < 0.01). Older age at infection (odds ratio [OR], 1.3; 95% CI, 1.1-1.4), malignancy (OR, 8.8; 95% CI, 2.6-32.9), unknown site of infection (OR, 12.7; 95% CI, 3.3-48.6), and minimal platelet count less than 100,000/µL in first 7 days of sepsis (OR, 5.0; 95% CI, 1.6-15.4) were identified as potential risk factors for AVN after sepsis following adjustment for multiple comparisons. Although rare, sepsis was associated with a higher risk of subsequent AVN than suspected bacterial infection in children. Older age, malignancy, unknown site of infection, and minimum platelet count were potential risk factors for AVN after sepsis.

Paediatric talus fractures: A guide to management based on a review of the literature

BackgroundTalus fractures are devastating injuries in both adults and children. Well recognised complications such as avascular necrosis (AVN), post-traumatic arthritis and non-union contribute to patient morbidity. This systematic review aimed to assess the literature on these injuries in children and their associated incidence, classification, management and outcome. MethodsA systematic review of Embase and Medline databases was carried out in accordance with PRISMA guidelines. Inclusion criteria were clinically orientated studies looking at talus fractures in paediatric patients (less than 18 years old). Exclusion criteria were conference abstracts, opinion-based reports, articles not published in English and articles published prior to 1980. Data extracted included patient demographics, fracture classification, management and outcomes. Results31 studies were included encompassing 143 patients and 167 fractures with a mean age of 11.9 years (1.2–18). The majority of fractures (43.7%, n = 73) were of the talar neck. 70.6% (n = 101) were managed operatively. The overall rate of AVN was 15.4% (n = 22), with a 96.5% union rate. Observed rates of AVN were 5.7% in Hawkin's 1, 11.8% in Hawkin's 2, 53.3% in Hawkin's 3 and 0 in Hawkin's 4 injuries. All cases of non-union occurred in children over 12 years, and seven children required arthrodesis (1x pantalar, 1x subtalar and 5x subtalar and tibiotalar) with a mean age of 14.4 years (9–17). ConclusionsTalus fractures are rare but potentially devastating injuries in children. This systematic review has shown comparable rates of AVN in children to their adult counterparts, with higher rates of non-union and arthrodesis in adolescent patients. A lower threshold for operative intervention to achieve anatomical reduction in these patients should be considered.

Effect of the Number, Size, and Location of Cannulated Screws on the Incidence of Avascular Necrosis of the Femoral Head in Pediatric Femoral Neck Fractures: A Review of 153 Cases.

The correlation between the number, size, and location of cannulated screws and the incidence of avascular necrosis (AVN) in children with femoral neck fractures treated surgically is uncertain. We retrospectively reviewed 153 children (mean age: 10.6±3.7 y) with femoral neck fractures treated by internal fixation with 2 (n=112) or 3 (n=41) cannulated screws. The severity of initial displacement was divided into incomplete (type I) and complete (type II, angulation <50 degrees; type III, angulation >50 degrees) fractures. The diameter of the screw was measured and recorded as a percentage of the femoral neck width. The distance (D) between the mid-point of each screw at the base (B) of the femoral neck and at the tip (T) of each screw and the superior and anterior cortices of the femoral neck, respectively, were measured on anteroposterior (AP) and lateral (L) radiographs. Values were expressed as the ratio between the measured distance and the width of the femoral neck (BDAP%, TDAP%, BDL%, and TDL%). The correlation between the number, size, and location of the screws and AVN was analyzed. Patients with type II of initial displacement treated with 2 cannulated screws had a lower AVN rate (21.4%) than those treated with 3 screws (44.8%) (P=0.027). Screw diameter (19%) in patients with AVN was larger than (17%) in patients without AVN (P<0.001); patients with AVN had a lower BDAP% (48.6%) than those without AVN (56.4%) (P<0.001). Screw size and BDAP% were risk factors for AVN (P<0.05). Further, screw diameter >16.5% and BDAP% <51.6% of the femoral neck width were the cutoff values for an increased AVN rate (P<0.05). Patients treated with 2 cannulated screws showed a lower rate of AVN than patients treated with 3 screws. Screws of larger size and screws closer to the piriformis fossa on AP radiographs increased the risk of AVN in children with femoral neck fractures treated surgically. Level III.

Reconstructive hip surgery in children with cerebral palsy: factors influencing risk of femoral head avascular necrosis.

Femoral head avascular necrosis (AVN) is a complication of hip reconstruction in children with cerebral palsy (CP) with uncertain incidence. The purpose of this study was to establish the rate of AVN in children undergoing hip reconstruction and to identify the factors associated with AVN. Medical records and radiographs of patients aged 1-18 with a diagnosis of CP who have undergone hip reconstruction over a 9-year period (2010-2018) with at least 1-year follow-up were reviewed. Age at time of surgery, sex, Gross Motor Function Classification System (GMFCS), procedure(s), preoperative migration percentage (MP), and signs of AVN on anterioposterior pelvis radiographs at routine follow-up visits (3 months, 6 months, and years 1-9, annually) according to the Bucholz-Ogden (BO) and Kalamchi-MacEwen (KM) classification systems were recorded. Univariate analysis was used to test for significance. Three hundred forty-nine hips in 209 patients met our inclusion criteria. Eleven hips (rate; 3%), in 11 patients, developed AVN. Classification of AVN was found to consist of: class I-4 (36%), class II-1 (9%), class III-[BO: 4 (36%)] [KM: 3 (27%)], and Class IV-[BO: 2 (18%)] [KM: 3 (27%)]. Average follow-up was of 3.5 years. The AVN cohort displayed older age (11.0 ± 2.8 vs. 8.1 ± 3.4; P = 0.005). Open reduction was associated with increased AVN, occurring in 9% of the hips (P = 0.004). No significant association was found between preoperative MP, GMFCS, or acetabular osteotomy. The method of open reduction (anterior vs. medial) was not significantly associated with AVN (P = 0.4471). In this large series, the observed rate of AVN was 3%, associated with open reductions at time of hip reconstruction. If possible, closed reduction would be preferred at time of hip reconstruction in children with CP to lower the risk of AVN. Level of evidence: III.

Comparison of salter osteotomy results in two different age groups in the treatment of developmental hip dislocation

Aim: Surgical treatment of developmental hip dislocation is highly challenging in children of walking age. The most common complications following surgery include avascular necrosis and redislocation. In this study, we aimed to compare the preoperative and postoperative acetabular index, avascular necrosis (AVN) and redislocation rates between two age groups of open reduction and Salter osteotomy in DDH (Developmental Dysplasia of the Hip). Methods: This prospective cohort study included patients who underwent open reduction and salter osteotomy for DDH between 2014 and 2017. Patients were grouped based on age as follows: Group 1: 18 -30 months old (n=44), Group 2: 31-48 months old (n=41). Preoperative, postoperative, and final acetabular indexes, AVN and redislocation rates were compared. Results: Among 85 patients included in the study, 20 were male and 65 were female. The mean ages of Groups 1 and 2 were 21.6 months and 38.5 months, respectively. Following surgery, Group 1 mean acetabular index reduced to 25.9 degrees from 35.1 degrees, while that of Group 2 decreased to 22.1 degrees from 33 degrees. AVN was present in 10 patients (22.72%) in Group 1 and 4 patients (9.75%) in Group 2. Conclusion: The acetabular index was adequately corrected in both groups. AVN was more frequent in children who had early interventions. We believe that the higher rate of avascular necrosis in children who underwent early intervention is due to surgical technique and using tighter sutures in the hip joint capsule.

Vaso-occlusive crisis as a predictor of symptomatic avascular necrosis in children with sickle cell disease.

Avascular necrosis (AVN) is a chronic bone complication of sickle cell disease (SCD) resulting in significant morbidity. Understanding associated risk factors can facilitate risk-based screening, earlier identification, and prompt intervention. Between 1998 and 2014, 26 symptomatic cases with imaging evidence of AVN were compared 1:5 with age- and SCD genotype-matched controls (n=128). Patients with 1-5 vaso-occlusive crisis (VOC) (OR 11.9, 95% CI, 1.4-99.9; P=0.02) and more than 5 VOC (OR 53.6, 95% CI, 5.5-520.2; P=0.0006) in a 5-year period were more likely to have AVN. Symptomatic patients with more than five VOC in 5 years may benefit from radiologic screening for AVN.

Prereduction traction for the prevention of avascular necrosis before closed reduction for developmental dysplasia of the hip: a meta-analysis.

Background and purposeAvascular necrosis (AVN) is one of the common complications after closed reduction and hip spica cast for developmental dysplasia of the hip (DDH). Prereduction traction has been used to reduce a dislocated hip or decrease the risk of AVN, but there are conflicting results in prevention effects on AVN. The purpose of this study was to systematically review the current literature and evaluate the effect of prereduction traction in preventing AVN in children with DDH treated by closed reduction through a meta-analysis.Materials and methodsA systematic review of the literature was performed using PubMed and EMBASE with variations of three major terms: 1) hip dislocation; 2) closed reduction; and 3) avascular necrosis. Seven studies that could compare the incidence of AVN between the traction and no-traction group were included. Methodological quality was assessed, a heterogeneity test was done (p=0.008), and the pooled risk ratios were estimated.ResultsThe association between traction and AVN was assessed, using data on 683 hips treated by closed reduction. The incidence of AVN in the traction and no-traction groups ranged from 5% to 47.7% and from 0% to 72.7%, respectively. A meta-analysis with a random effects model indicated no significant difference in the incidence of AVN between traction and no-traction groups (p=0.536).ConclusionThere was insufficient evidence to decide the efficacy of prereduction traction before closed reduction in reducing the risk of AVN in patients with DDH in this meta-analysis. To recommend prereduction traction for the prevention of AVN, long-term follow-up studies considering age, severity of dislocation, and appropriate traction method are needed.

Avascular necrosis in children with cerebral palsy after reconstructive hip surgery.

PurposeProgressive hip displacement is one of the most common orthopaedic pathologies in children with cerebral palsy (CP). Reconstructive hip surgery has become the standard treatment of care. Reported avascular necrosis (AVN) rates for hip reconstructive surgery in these patients vary widely in the literature. The purpose of this study is to identify the frequency and associated risk factors of AVN for reconstructive hip procedures.MethodsA retrospective analysis was performed of 70 cases of reconstructive hip surgery in 47 children with CP, between 2009 and 2013. All 70 cases involved varus derotation osteotomy (VDRO), with 60% having combined VDRO and pelvic osteotomies (PO), and 21% requiring open reductions. Mean age at time of surgery was 8.82 years and 90% of patients were Gross Motor Function Classification System (GMFCS) 4 and 5. Radiographic dysplasia parameters were analysed at selected intervals, to a minimum of one year post-operatively. Severity of AVN was classified by Kruczynski's method. Bivar- iate statistical analysis was conducted using Chi-square test and Student's t-test.ResultsThere were 19 (27%) noted cases of AVN, all radio- graphically identifiable within the first post-operative year. The majority of AVN cases (63%) were mild to moderate in severity. Pre-operative migration percentage (MP) (p = 0.0009) and post-operative change in MP (p = 0.002) were the most significant predictors of AVN. Other risk factors were: GMFCS level (p = 0.031), post-operative change in NSA (p = 0.02) and concomitant adductor tenotomy (0.028).ConclusionAVN was observed in 27% of patients. Severity of displacement correlates directly with AVN risk and we suggest that hip reconstruction, specifically VDRO, be performed early in the 'hip at risk' group to avoid this complication.

Inter-observer and intra-observer reliability in the radiographic diagnosis of avascular necrosis of the femoral head following reconstructive hip surgery in children with cerebral palsy.

PurposeThe incidence of avascular necrosis (AVN) following reconstructive hip surgery in cerebral palsy (CP) ranges from 0 to 69 % in the current literature. The purpose of this study was to determine the inter- and intra-observer reliability of radiographically diagnosing AVN in children with CP after hip surgery.MethodsA retrospective review of 65 children with CP who had reconstructive hip surgery between 2009 and 2012 at BC Children’s Hospital was completed. Anterior–posterior and lateral radiographs were presented to four pediatric orthopaedic surgeons over two rounds. Surgeons were asked to review the set of unidentified radiographs and comment ‘yes’ or ‘no’ for the presence of AVN. Two weeks later the same set of radiographs was sent in a different order and the surgeons were again asked to comment on AVN. Inter- and intra-observer reliability was determined using kappa statistics.ResultsThe intra-observer reliability ranged from 0.65 to 0.88 with an average score of 0.76. Inter-observer reliability showed greater variability, ranging from 0.41 to 0.77 with an average score of 0.56 across all surgeons.ConclusionsAlthough the intra-rater reliability produced a strength of “good” and the inter-rater reliability a strength of “moderate” agreement, the variability within these scores is clinically important as it demonstrates the difficulty in identifying AVN. This may explain the variability in AVN that is reported in the literature. The need for further education and research in the diagnosis of AVN in children with CP who have undergone reconstructive hip surgery is clinically necessary.

Avascular necrosis in children with cerebral palsy after reconstructive hip surgery

Avascular necrosis in children with cerebral palsy after reconstructive hip surgery

Older Age, Use Of Myeloablative Regimens For Malignant Diseases and Chronic Graft-Versus-Host Disease Are Risk Factors For Avascular Necrosis Of Bone After Allogeneic Hematopoietic Cell Transplantation In Children and Adolescents

▪Avascular necrosis (AVN) of the bone is a painful and debilitating complication of allogeneic hematopoietic cell transplantation (HCT) that is associated with significant morbidity and often requires surgery. Risk factors for its development in pediatric allogeneic HCT recipients are not well described. To assess risk factors for AVN in children and adolescents following allogeneic HCT, we conducted a nested case-control study with a matched cohort of 638 patients reported to the Center of International Blood and Marrow Transplant Research who were ≤ 21 years of age, received their first allogeneic transplant between 1990 to 2008 in the United States and had survived ≥ 6 months from HCT. Overall, 160 cases with AVN were identified. Each case was matched with up to 3 controls by same year of HCT, similar length of follow-up and by transplant center (478 controls). Cases and controls were confirmed via central review of radiology, pathology and/or surgical procedure reports. The median age for cases was 15 (range 2-21) years, 49% were male, 65% had acute leukemia, 65% had received high-dose total body irradiation (TBI) based conditioning regimen, and 65% had received unrelated donor HCT. Among cases, 18% had a history of acute graft-versus-host disease (GVHD) while 56% had a history of chronic GVHD prior to development of AVN. Median time from HCT to diagnosis of AVN was 14 (range <1-172) months. We evaluated age, gender, diagnosis, conditioning regimen, TBI, donor source and GVHD as risk factors for AVN. On conditional logistic regression, increasing age at HCT, female gender and chronic GVHD were significantly associated with increased risks of AVN. Compared to patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with non-malignant diseases and those who had received reduced intensity conditioning regimen for malignant diseases. (Table). Patients receiving unrelated donor transplant had lower risks of AVN compared to HLA-identical sibling donor HCT recipients; there was no significant interaction between donor source and GVHD status. Lack of data on pre- and post-HCT steroid exposure was a limitation of our study. Our findings suggest that children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to high-dose myeloablative conditioning regimens and immunosuppression post-HCT for the treatment of GVHD. Our study identifies important risk factors for AVN in a large cohort of pediatric HCT recipients. Future studies should evaluate the role of surveillance and preventive strategies for AVN in pediatric HCT recipients who are at high risk for development of AVN. Disclosures:No relevant conflicts of interest to declare.

Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: A systematic review of the literature

Puberty, obesity, endocrine and chronic systemic diseases are known to be associated with slipped capital femoral epiphysis (SCFE). The mechanical insufficiency of the physis in SCFE is thought to be the result of an abnormal weakening of the physis. However, the mechanism at the cellular level has not been unravelled up to now. To understand the pathophysiology of endocrine and metabolic factors acting on the physis, we performed a systematic review focussing on published studies reporting on hormonal, morphological and cellular abnormalities of the physis in children with SCFE. In addition, we looked for studies of the effects of endocrinopathies on the human physis which can lead to cause SCFE and focussed in detail on hormonal signalling, hormone receptor expression and extracellular matrix (ECM) composition of the physis. We searched in the PubMed, EMBASE.com and The Cochrane Library (via Wiley) databases from inception to 11th September 2012. The search generated a total of 689 references: 382 in PubMed, 232 in EMBASE.com and 75 in The Cochrane Library. After removing duplicate papers, 525 papers remained. Of these, 119 were selected based on titles and abstracts. After excluding 63 papers not related to the human physis, 56 papers were included in this review. Activation of the gonadal axis and the subsequent augmentation of the activity of the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis are important for the pubertal growth spurt, as well as for cessation of the physis at the end of puberty. The effects of leptin, thyroid hormone and corticosteroids on linear growth and on the physis are also discussed. Children with chronic diseases suffer from inflammation, acidosis and malnutrition. These consequences of chronic diseases affect the GH-IGF-1 axis, thereby, increasing the risk of the development of SCFE. The risk of SCFE and avascular necrosis in children with chronic renal insufficiency, growth hormone treatment and renal osteodystrophy remains equivocal. SCFE is most likely the result of a multi-factorial event during adolescence when height and weight increase dramatically and the delicate balance between the various hormonal equilibria can be disturbed. Up to now, there are no screening or diagnostic tests available to predict patients at risk.

Magnetic resonance imaging in children with sickle cell disease—detecting alterations in the apparent diffusion coefficient in hips with avascular necrosis

Avascular necrosis (AVN) is a common morbidity in children with sickle cell disease (SCD) that leads to pain and joint immobility. However, the diagnosis is often uncertain or delayed. To examine the ability of apparent diffusion coefficient (ADC) measurements on diffusion-weighted imaging to detect AVN in children with SCD. ADC values were calculated at the hips of normal children (n = 19) and children with SCD who were either asymptomatic with no known previous hip disease (n = 13) or presented for the first time with clinical symptoms of hip pathology (n = 12). ADC values were compared for differences among groups with and without AVN using non-parametric statistical methods. The ADC values were elevated in the hips of children with AVN (median ADC = 1.57 × 10(-3) mm(2)/s [95% confidence interval = 0.86-2.10]) and differed significantly in pairwise comparisons (all P < 0.05) from normal children (0.74 [0.46-0.98]), asymptomatic children with SCD (0.55 [0.25-0.85]), and SCD children who had symptoms referable to their hips but did not show findings of hip AVN on conventional MRI or radiographs (0.46 [0.18-0.72]). Children with sickle cell disease have elevated apparent diffusion coefficient values in their affected hips on initial diagnosis of avascular necrosis.

Fractures and avascular necrosis in children receiving chemotherapy for acute lymphoblastic leukaemia

Fractures and avascular necrosis in children receiving chemotherapy for acute lymphoblastic leukaemia

Multiple-choice questionnaire: general

Concerning avascular necrosis (AVN) of the femoral head in children: (a) Idiopathic AVN (Legg Calve Perthes) disease affects approximately 1 in 1000 to 5000 children. (b) Idiopathic AVN has a male sex predilection of 5:1. (c) Idiopathic AVN is bilateral in up to 10% of cases. (d) There is an increased risk of developing AVN in children with chronic renal failure which is independent of steroid therapy. (e) AVN has an equal sex incidence in chronic renal failure.

Avascular necrosis of the femoral head in children with chronic renal disease.

To determine the incidence of avascular necrosis (AVN) of the femoral head in children with chronic renal failure. Pelvic radiographs in 205 children (age range, 6 months to 16 years; mean age, 6 years +/- 3.5 [SD]) with chronic renal failure were reviewed. Serial radiographs were obtained every 6 months for 1-7 years (mean, 3 years +/- 2) to assess the presence of AVN of the femoral head; six children had metabolic renal disease, 21 had acquired renal disease, and 178 had structural renal lesions. Radiographic findings of AVN were seen in 14 of 205 patients (approximately one in every 15). The frequency of AVN was similar in boys and girls; AVN was observed in 11 (6.9%) of 159 boys and in three (6.5%) of 46 girls and was not related to the duration of renal disease, type of renal disease, or growth hormone therapy. Affected children were frequently asymptomatic, and, when present, the clinical complaints were mild. In two instances, AVN developed while the patients were receiving corticosteroids before entering this study. The results of this study indicate that AVN of the femoral head is a frequent complication in children with chronic renal failure, occurring in approximately 7% of this population. Unlike Legg-Calvé-Perthes disease, AVN in children with chronic renal failure is frequently asymptomatic and has no sex predilection.