Jun-Dong Chang

Genetic Background of Nontraumatic Osteonecrosis of the Femoral Head in the Korean Population

AbstractMajor thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH) in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in 71 patients (53 men, 18 women) with ONFH. We classified these patients as 51 alcohol-induced, 18 idiopathic, one steroid-induced, and one dysbaric. We recruited 200 normal control subjects (128 men, 72 women). We used multiplex PCR/restriction fragment length polymorphism for each genotyping. We observed neither factor V Leiden nor prothrombin G20210A mutation. Although methylenetetrahydrofolate reductase A1298C genotypes were not associated with osteonecrosis, methylenetetrahydrofolate reductase C677T variant genotypes increased the risk of ONFH compared with 677CC. Odds ratios of 677CT and 677CT+TT were 2.00 (95% confidence interval, 1.05–3.81) and 1.96 (95% confidence interval, 1.07–3.59), respectively, compared with 677CC. Our data suggest methylenetetrahydrofolate reductase C677T polymorphism plays a role in the pathogenesis of osteonecrosis in the Korean population. It also implies the genetic risk profile of ONFH may differ among ethnic populations. Level of Evidence: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

The effect of TNFα secreted from macrophages activated by titanium particles on osteogenic activity regulated by WNT/BMP signaling in osteoprogenitor cells

Wear particles are the major cause of osteolysis associated with failure of implant following total joint replacement. During this pathologic process, activated macrophages mediate inflammatory responses to increase osteoclastogenesis, leading to enhanced bone resorption. In osteolysis caused by wear particles, osteoprogenitors present along with macrophages at the implant interface may play significant roles in bone regeneration and implant osteointegration. Although the direct effects of wear particles on osteoblasts have been addressed recently, the role of activated macrophages in regulation of osteogenic activity of osteoblasts has scarcely been studied. In the present study, we examined the molecular communication between macrophages and osteoprogenitor cells that may explain the effect of wear particles on impaired bone forming activity in inflammatory bone diseases. It has been demonstrated that conditioned medium of macrophages challenged with titanium particles (Ti CM) suppresses early and late differentiation markers of osteoprogenitors, including alkaline phosphatase (ALP) activity, collagen synthesis, matrix mineralization and expression of osteocalcin and Runx2. Moreover, bone forming signals such as WNT and BMP signaling pathways were inhibited by Ti CM. Interestingly, TNFα was identified as a predominant factor in Ti CM to suppress osteogenic activity as well as WNT and BMP signaling activity. Furthermore, Ti CM or TNFα induces the expression of sclerostin (SOST) which is able to inhibit WNT and BMP signaling pathways. It was determined that over-expression of SOST suppressed ALP activity, whereas the inhibition of SOST by siRNA partially restored the effect of Ti CM on ALP activity. This study highlights the role of activated macrophages in regulation of impaired osteogenic activity seen in inflammatory conditions and provides a potential mechanism for autocrine regulation of WNT and BMP signaling mediated by TNFα via induction of SOST in osteprogenitor cells.

Third-Generation Ceramic-on-Ceramic Bearing Surfaces in Revision Total Hip Arthroplasty

With an increase of revision total hip arthroplasty (THA), the choice of bearing surface becomes more important. Wear debris by conventional metal-on-polyethylene articulations may cause extensive osteolysis, especially in young patients. We analyzed the clinical and radiographic outcomes after revision THA using third-generation ceramic-on-ceramic bearing surfaces in 42 hips. The mean age of the patients was 48.8 years (32-59 years), and the mean duration of follow-up monitoring was 5.4 years (3.2-8.0 years). At final follow-up examination, the average Harris Hip Score was 91.3. Although minor complications were observed in 6 hips (14.3%), no hips required additional revision surgery. No hip showed radiolucent lines, acetabular cup migration, or osteolysis. Our data show that clinical and radiographic outcomes after revision THA using third-generation ceramic-on-ceramic bearing surfaces are favorable. Ceramic-on-ceramic bearing surfaces can be preferentially considered for revision THA, especially in young patients. Further studies with long-term follow-up data are warranted.

Risk factors for contra-lateral hip fracture in elderly patients with previous hip fracture.

INTRODUCTION Contra-lateral hip fractures in elderly patients with a previous hip fracture increase the incidence of complications and socioeconomic burden. The purpose of this study was to identify the risk factors that contribute to the occurrence of contra-lateral hip fracture in elderly patients. MATERIALS AND METHODS Among 1093 patients treated for a hip fracture, 47 patients sustained a contra-lateral hip fracture. These patients were compared with 141 patients with a unilateral hip fracture (controls). RESULTS The incidence of contra-lateral hip fracture was 4.3% among the 1093 patients treated for a hip fracture at our institute. A contra-lateral hip fracture occurred within 2 years of initial fracture in 66%, and subsequently, the annual incidence rate decreased. A similar fracture pattern was noted in 70% of patients who sustained an intertrochanteric fracture. In terms of preoperative factors, respiratory disease (OR 2.57, P=0.032) and visual impairment (OR 2.51, P=0.012) were higher in patients with a contra-lateral hip fracture than in controls, and for postoperative factors, the proportions of patients with postoperative delirium (OR 2.91, P=0.022), late onset of rehabilitation (OR 1.05, P=0.023), and poor ambulatory status at 3 months (OR 1.34, P=0.002) were also significantly higher in patients than in controls. CONCLUSIONS Postoperative delirium and underlying visual impairment and respiratory disease could be risk factors of contra-lateral fracture in elderly patients. Early and active rehabilitation after surgery is important to prevent the occurrence of contra-lateral hip fracture in the elderly.

Suppression of osteogenic activity by regulation of WNT and BMP signaling during titanium particle induced osteolysis.

Periprosthetic osteolysis remains the leading obstacle for total joint replacements. Primarily, it was thought that aseptic loosening is mainly caused by macrophage mediated inflammatory process arising from production of wear debris. The role of osteoclasts and its sequential bone resorption ability has been extensively studied, but little is known about impaired osteogenesis during osteolysis. In the current study, we have tried to delineate the regulatory mechanism of osteogenic signals by Ti particles in osteoprogenitor cells as well its participatory role in wear debris induced osteolysis. Implantation of Ti particles on mice calvaria induced pro-inflammatory response, elevated expression of COX2 and reduced the expression of Osterix. Treatment of Ti particles to MC3T3 E-1 cells displayed decreased osteogenic activity including ALP activity, mineralization and mRNA levels several osteogenic genes. Moreover, the basal activity of WNT and BMP signaling pathways was suppressed in MC3T3 E-1 cells treated with Ti particles. As an early response to Ti particles, MC3T3 E-1 cells showed activation of ERK and JNK. Co-inhibition of ERK and JNK with their specific inhibitors resulted in partial recovery of WNT and BMP signaling activity as well as ALP activity and collagen synthesis. Finally, LiCl mediated activation of WNT signaling pathway demonstrated rescue of Ti particle facilitated suppression of Osterix expression in mice calvaria. Our results provide evidences that WNT signaling pathway is regulated by ERK, JNK, and BMP signaling pathway during wear debris induced inflammatory osteolysis and may be considered as suitable therapeutic targets for the treatment.

Effects of hyaluronic acid and γ-globulin concentrations on the frictional response of human osteoarthritic articular cartilage.

Synovial fluid plays an important role in lubricating synovial joints. Its main constituents are hyaluronic acid (HA) and γ–globulin, acting as boundary lubricants for articular cartilage. The aim of the study was to demonstrate the concentration-dependent effect of HA and γ–globulin on the boundary-lubricating ability of human osteoarthritis (OA) cartilage. Normal, early and advance stage articular cartilage samples were obtained from human femoral heads and in presence of either HA or γ–globulin, cartilage frictional coefficient (µ) was measured by atomic force microscopy (AFM). In advanced stage OA, the cartilage superficial layer was observed to be completely removed and the damaged cartilage surface showed a higher µ value (∼0.409) than the normal cartilage surface (∼0.119) in PBS. Adsorbed HA and γ–globulin molecules significantly improved the frictional behavior of advanced OA cartilage, while they were ineffective for normal and early OA cartilage. In advanced-stage OA, the concentration-dependent frictional response of articular cartilage was observed with γ–globulin, but not with HA. Our result suggested that HA and γ–globulin may play a significant role in improving frictional behavior of advanced OA cartilage. During early-stage OA, though HA and γ–globulin had no effect on improving frictional behavior of cartilage, however, they might contribute to disease modifying effects of synovial fluid as observed in clinical settings.

A Novel Method for the Accurate Evaluation of Poisson’s Ratio of Soft Polymer Materials

A new method with a simple algorithm was developed to accurately measure Poissons ratio of soft materials such as polyvinyl alcohol hydrogel (PVA-H) with a custom experimental apparatus consisting of a tension device, a micro X-Y stage, an optical microscope, and a charge-coupled device camera. In the proposed method, the initial positions of the four vertices of an arbitrarily selected quadrilateral from the sample surface were first measured to generate a 2D 1st-order 4-node quadrilateral element for finite element numerical analysis. Next, minimum and maximum principal strains were calculated from differences between the initial and deformed shapes of the quadrilateral under tension. Finally, Poissons ratio of PVA-H was determined by the ratio of minimum principal strain to maximum principal strain. This novel method has an advantage in the accurate evaluation of Poissons ratio despite misalignment between specimens and experimental devices. In this study, Poissons ratio of PVA-H was 0.44 ± 0.025 (n = 6) for 2.6–47.0% elongations with a tendency to decrease with increasing elongation. The current evaluation method of Poissons ratio with a simple measurement system can be employed to a real-time automated vision-tracking system which is used to accurately evaluate the material properties of various soft materials.

Acute Delayed or Late Infection of Revision Total Hip Arthroplasty Treated with Debridement/Antibiotic-loaded Cement Beads and Retention of the Prosthesis

Purpose The treatment of infected revision total hip arthroplasty (THA) is very challenging due to retained revision prosthesis, poor bone stock and soft tissue condition derived from previous revision surgeries, and comorbidities. The purpose of this study was to investigate the effectiveness and short-term outcomes of aggressive debridement and use of antibiotic-loaded cement beads with retention of the prosthesis for acute delayed or late infection of revision THAs. Materials and Methods Ten consecutive patients with symptoms or signs of less than one-week evolution and well-fixed prostheses, were treated with this procedure and a postoperative course of organism-specific antibiotics for a minimum of 6 weeks. All hips presented with acute delayed or late infection of revision THAs. Patients with a mean age of 68.1 years (range, 59-78 years) underwent an average of 1.9 previous revision THAs (1-4) before the index surgery. The minimal follow-up was 2 years with a mean of 46.2 months (range, 24-64 months). Results There were 8 cures (80.0%) and 2 failures with no mortality during the study period. The 2 failures involved the same and resistant bacteria implicated in the primary infection (methicillin-resistant Staphylococcus aureus and Prevotella oralis, respectively). The mean Harris hip score was 65.2 (range, 26-83) and the mean visual analogue scale was 2.6 (range, 1-4) at final follow-up. Conclusion With a favorable success rate and no mortality, our procedure may be considered a safe and effective alternative for the treatment of acute delayed or late infection of revision THAs with well-fixed prostheses.

Roles of Cellular and Molecular Targets of Wear Debris in Periprosthetic Osteolysis

Wear-generated particulate debris is the main cause of initiating this destructive process. We present recent advances in understanding of how wear debris causes osteolysis in the aspect of cellular and molecular biological levels. Macrophages, the most important cellular target for wear debris, respond to particle challenge in two distinct ways of pro-inflammatory signaling and inhibition of the protective actions of anti-osteoclastogenic cytokines, finally leading to suppression of osteogenic activity as well as increased osteoclast activity. At a molecular level, such alterations of cellular activities occur through MAP kinase, transcription factors including NF-κB, Wnt/β-catenin signaling and cytokine signaling cascades in various kinds of cells.

Midterm outcome of fourth-generation ceramic-on-ceramic bearing surfaces in revision total hip arthroplasty

Purpose: The purpose of this study is to evaluate the clinical and radiologic outcomes after revision total hip arthroplasty (THA) using fourth-generation ceramic-on-ceramic (CoC) bearing surfaces. Methods: A total of 52 revision THAs (28 men and 19 women) using the fourth-generation CoC bearing surfaces were retrospectively evaluated. Both acetabular cup and femoral stem were revised in all cases. The mean follow-up period was 7.3 years (range, 4.0–9.9 years). The clinical results with Harris hip score (HHS), Western Ontario McMaster Osteoarthritis Index (WOMAC), and radiologic outcomes were evaluated. Results: At the final follow-up examination, the average HHS was 90.4 (range, 67–100). The average WOMAC pain and physical function score were 2.8 (range, 0–12) and 16.4 (range, 0–42), respectively. Complications were observed in 10 hips (19.2%). However, there were no bearing surface-related complications, and no cases of dislocation and squeaking. Retroacetabular pelvic osteolysis without cup loosening was observed in one hip at the final follow-up. However, no hip showed radiographic signs of cup loosening, vertical or horizontal acetabular cup migrations, and changes of inclinations during the follow-up period. Conclusion: Our data showed that clinical and radiologic outcomes after revision THA using fourth-generation CoC bearing were favorable. Hence, revision THA with the use of CoC bearing surfaces can be preferentially considered. Further studies with long-term follow-up data are warranted.