Legg‐Calvé‐Perthes Disease Produces Chronic Hip Synovitis and Elevation of Interleukin‐6 in the Synovial Fluid

Legg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD. Serial MRI was performed on 28 patients. T2‐weighted and gadolinium‐enhanced MR images were used to assess synovial effusion and synovial enhancement (hyperemia) over time. A multiple‐cytokine assay was used to determine the levels of 27 inflammatory cytokines and related factors present in the synovial fluid from 13 patients. MRI analysis showed fold increases of 5.0 ± 3.3 and 3.1 ± 2.1 in the synovial fluid volume in the affected hip compared to the unaffected hip at the initial and the last follow‐up MRI, respectively. The mean duration between the initial and the last MRI was 17.7 ± 8.3 months. The volume of enhanced synovium on the contrast MRI was increased 16.5 ± 8.5 fold and 6.3 ± 5.6 fold in the affected hip compared to the unaffected hip at the initial MRI and the last follow‐up MRI, respectively. In the synovial fluid of the affected hips, IL‐6 protein levels were significantly increased (LCPD: 509 ± 519 pg/mL, non‐LCPD: 19 ± 22 pg/mL; p = 0.0005) on the multi‐cytokine assay. Interestingly, IL‐1β and TNF‐α levels were not elevated. In the active stage of LCPD, chronic hip synovitis and significant elevation of IL‐6 are produced in the synovial fluid. Further studies are warranted to investigate the role of IL‐6 on the pathophysiology of synovitis in LCPD and how it affects bone healing. © 2015 American Society for Bone and Mineral Research     

Combination Treatment of Biomechanical Support and Targeted Intra‐arterial Infusion of Peripheral Blood Stem Cells Mobilized by Granulocyte‐Colony Stimulating Factor for the Osteonecrosis of the Femoral Head: A Randomized Controlled Clinical Trial

The objective of this study was to determine the benefits of combination treatment with mechanical support and targeted intra‐arterial infusion of peripheral blood stem cells (PBSCs) mobilized by granulocyte–colony stimulating factor (G‐CSF) via the medial circumflex femoral artery on the progression of osteonecrosis of the femoral head (ONFH). Fifty‐five patients (89 hips) with early and intermediate stage ONFH were recruited and randomly assigned to combination treatment or mechanical support treatment (control group). All hips received mechanical support treatment (porous tantalum rod implantation). Then, hips in the combination treatment group were performed targeted intra‐arterial infusion of PBSCs. At each follow‐up, Harris hip score (HHS) and Association Research Circulation Osseous (ARCO) classification were used to evaluate the symptoms and progression of osteonecrosis. Total hip arthroplasty (THA) was assessed as an endpoint at each follow‐up. At 36 months, 9 of the 41 hips (21.95%) in the control group progressed to clinical failure and underwent THA whereas only 3 of the 48 hips (6.25%) in the combination treatment group required THA (p = 0.031). Kaplan‐Meier survival analysis showed a significant difference in the survival time between the two groups (log‐rank test; p = 0.025). Compared to the control group, combination treatment significantly improved the HHS at 36 months (p = 0.003). At the final follow‐up examination, radiological progression was noted in 13 of 41 hips (31.71%) for the control group, but in only 4 of 48 hips (8.33%) for the combination treatment group (p = 0.005). The overall collapse rates were 15.15% (5/33 hips) and 8.11% (3/37 hips) in the control and combination treatment groups, respectively. Targeted intra‐arterial infusion of PBSCs is capable of enhancing the efficacy of biomechanical support in the treatment of ONFH. This clinical trial confirmed that the combination treatment might be a safe and feasible choice for the treatment of early or intermediate stages of ONFH. © 2014 American Society for Bone and Mineral Research.     

Influence of Factors Regulating Bone Formation and Remodeling on Bone Quality in Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) usually affects young individuals and has a major impact on lifestyle. Notably, the pathogenetic mechanisms of osteonecrosis are unresolved and no effective treatment exists. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2, osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to those of patients with primary osteoarthritis (OA). The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by micro-computed tomographic analysis. Our results demonstrate that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with ONFH. We observed increased extracellular osteocalcin deposition, presumably caused by a higher number of osteoblasts in concordance with increased activity of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast differentiation rate in ONFH bone. We found no significant change in bone volume, connectivity, and structural model index; further, no significant differences were detected for trabecular properties in ONFH bone. In conclusion, we have shown increased gene expression of factors regulating bone formation and remodeling in the femoral head and/or neck of patients with ONFH. Further, we observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte cell number, while no significant changes in trabecular microarchitecture were detected. This study increases our understanding of the pathophysiology and repair process following ONFH and might help in the development of new treatment strategies in the future.     

Risk Factors and Outcomes Associated with Intraoperative Fractures during Short-Stem Total Hip Arthroplasty for Osteonecrosis of the Femoral Head

BackgroundYoung age in osteonecrosis of the femoral head (ONFH) demands bone-preserving, short-stem arthroplasty. Several designs including neck-preserving stems and neck-resecting, shortened, standard stems are classified as short stems. There is a paucity of literature investigating risk factors and outcomes of intraoperative complications of neck preserving, short-stem arthroplasty in ONFH.MethodsA total of 107 hips operated with METHA short-stem arthroplasty for ONFH were retrospectively evaluated. The mean age of patients was 43.7 years (range, 27–60 years). Nine patients had an intraoperative fracture. Seven hips received prophylactic cerclage wiring for poor bone quality. Patients were invited for clinical and radiological evaluation at the latest follow-up.ResultsThe mean follow-up of patients was 47.2 months. Significant association with intraoperative fractures and the need for prophylactic cerclage wiring were found in steroids-, alcohol-, and chronic renal failure-induced ONFH. However, patient sex, body mass index, traumatic/idiopathic ONFH, previous implant in situ, prosthesis size, and single-sitting bilateral total hip replacement (THA) were not the risk factors. All hips showed signs of osteointegration at final follow-up. No revision was done during the study period for any cause.ConclusionsMETHA short-stem THA offers excellent functional and radiological outcomes in ONFH. However, precaution must be exercised in patients with steroids-, alcohol-, and renal disorders-induced ONFN due to poor bone quality and higher chances of intraoperative fractures. Also, additional measures such as the use of a high-speed burr and prophylactic cerclage wiring in ONFH may allow predictable and safe use of short stems.     

Clinical Outcome of Surgical Hip Dislocation Combined with Impacting Bone Grafts and Implanting Iliac Bone Flaps in the Treatment of Osteonecrosis of the Femoral Head: A Mid‐term Retrospective Study

ObjectiveTo report the medium‐term outcomes of surgical hip dislocation (SHD) combined with impacting bone grafts and implanting iliac bone flaps in the treatment of osteonecrosis of the femoral head (ONFH) and to define the indications for this treatment.MethodsThis was a single‐center retrospective study. In total, 64 patients (70 hips) with ONFH treated from January 2014 to December 2017 were included in this study. There were 51 males and 13 females aged 18–55 years with an average age of 32 years. All patients underwent surgery for SHD combined with impacting bone grafts and implanting iliac bone flaps. Preoperative and postoperative clinical outcomes were assessed. The clinical outcome was assessed using the Harris hip score (HHS) and the conversion rate of total hip arthroplasty (THA). Univariate and multivariate logistic regression analyses were performed to identify risk factors affecting the clinical outcome. Kaplan–Meier (K‐M) analysis was applied to calculate the survival rate of the femoral head.ResultsAt the last follow‐up (60 ± 15.08 months), the HHS was excellent for 41 hips, good for 17 hips, fair for three hips, and poor for nine hips. All nine hips with poor HHS underwent THA, including five in the first 2 years following the index surgery and four between three and 5 years. The conversion rate of total hip arthroplasty was 12.86%. Univariate and multivariate logistic regression analyses showed that the duration of hip pain and JIC classification type were significantly associated with clinical outcomes. Elderly age and advanced ONFH stage tended to lead to worse surgical outcomes. The overall survival rate of JIC classification type C1 and duration of pain ≤6 months was 98.1% and 97.8% at 72 months, respectively, as estimated by the Kaplan–Meier method.ConclusionSurgical hip dislocation combined with impacting bone grafts and implanting iliac bone flaps in the treatment of ONFH had a good mid‐term clinical outcome, especially for patients with retention of the lateral column of the femoral head and hip pain less than 1 year.     

Degree of Mineralization-related Collagen Crosslinking in the Femoral Neck Cancellous Bone in Cases of Hip Fracture and Controls

Based on the present definition of osteoporosis, both bone density and quality are important factors in the determination of bone strength. Collagen crosslinking is a determinant of bone quality. Cross-links can form enzymatically by the action of lysyl oxidase or non-enzymatically, resulting in advanced glycation end products. Collagen crosslinking is affected by tissue maturation as well as the degree of mineralization. Homocysteine and vitamin B6 (pyridoxal) are also regulatory factors of collagen crosslinking. We elucidate the relationship between the degree of mineralization and collagen cross-links in cancellous bone from hip fracture cases. We also determined plasma levels of homocysteine and pyridoxal. Twenty-five female intracapsular hip fracture cases (78 ± 6 years) and 25 age-matched postmortem controls (77 ± 6 years) were included in this study. Collagen crosslinking was analyzed after each bone specimen was fractionated into low (1.7–2.0 g/ml) and high (>2.0 g/ml) density fractions. The content of enzymatic (immature reducible and mature nonreducible cross-links) and nonenzymatic cross-link (pentosidine) were determined. In the controls, there was no difference in total enzymatic cross-links between low and high density bone, while pentosidine content was significantly higher in high density bone. In the fracture cases, not only reduced enzymatic cross-links in high density bone and increased pentosidine in both low and high density bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls. These results indicate that detrimental crosslinking in both low and high mineralized bone result in impaired bone quality in osteoporotic patients. All authors have no Conflict of interest policy.     

Borderline Developmental Dysplasia of the Hip: A Risk Factor Predicting the Development and Poor Prognosis after Core Decompression for Idiopathic Osteonecrosis of the Femoral Head

ObjectiveIt is unclear whether idiopathic osteonecrosis of the femoral head (ONFH) is associated with borderline developmental dysplasia of the hip (BDDH). This study aimed to compare the incidence of BDDH between patients with idiopathic ONFH and matched control subjects and determine the influence of BDDH on poor prognosis after core decompression (CD).MethodsWe retrospectively examined 78 consecutive patients (111 hips) with idiopathic ONFH undergoing CD and 1:2 matched with 156 control subjects (222 hips). The anteroposterior pelvic radiographs were used to measure the acetabular anatomical parameters and divide included subjects into BDDH or non‐BDDH group. The incidence of BDDH and acetabular anatomical parameters were compared between patients with idiopathic ONFH and matched controls. Clinical outcomes, such as Harris Hip Score (HHS), progression of collapse, and conversion to total hip arthroplasty (THA), were compared between patients with BDDH and without BDDH in the idiopathic ONFH group, with a mean follow‐up of 72.1 ± 36.6 months.ResultsPatients with idiopathic ONFH had a significantly higher incidence of BDDH than matched controls (29.7% vs 12.2%, p < 0.001). Less acetabular coverage was also found in patients with idiopathic ONFH than in matched controls as demonstrated by lower CEA (28.5° ± 4.7° vs 33.1° ± 5.7°, p < 0.001), AHI (82.4 ± 5.0 vs 86.3 ± 5.4, p < 0.001), ADR (299.6 ± 28.4 vs 318.8 ± 31.3, p < 0.001), and a higher sharp angle (40.0° ± 3.4° vs 37.4° ± 3.7°, p < 0.001). In patients with idiopathic ONFH, the BDDH group had a significantly lower mean HHS at the last follow‐up (83.5 ± 17.4 vs 91.6 ± 9.7, p = 0.015) with a different score distribution (p = 0.004), and a lower 5‐year survival rate with both clinical failure (66.7%, 95% CI 52.4%–84.9% vs 83.7%, 95% CI 75.2%–93.1%; p = 0.028) and conversion to THA (74.6%, 95% CI 60.7%–91.6% vs 92.1%, 95% CI 85.6%–99.0%; p = 0.008) as the endpoints than the non‐BDDH group.ConclusionThe incidence of BDDH was significantly higher in patients with idiopathic ONFH than matched controls, and idiopathic ONFH patients who underwent CD with BDDH had lower mean HHS as well as 5‐year survival rate than those without BDDH. Therefore, BDDH should be considered a risk factor predicting the development of idiopathic ONFH as well as poor prognosis after CD.