Preventive effects of tamsulosin for postoperative urinary retention after lower limb arthroplasty: A randomized controlled study.

PURPOSE: This prospective, randomized, controlled study investigated the use of tamsulosin, a selective alpha-blocker, as a prophylactic medication to prevent postoperative urinary retention (POUR) following lower limb arthroplasty. MATERIALS AND METHODS: The criterion for diagnosing POUR was used a postoperative bladder volume over 400 mL with incomplete emptying. Patients who underwent primary total hip or knee arthroplasty were randomly assigned at a 1:1 ratio to tamsulosin treatment and non-treatment groups at a single center from September 2018 to November 2018. The treatment group received 0.2 mg of tamsulosin orally once at night for 3 days starting on postoperative day 1. During this 3-day period, an indwelling Foley catheter was maintained. The incidence of POUR according to tamsulosin treatment following lower limb arthroplasty was the primary outcome. RESULTS: In total, 100 patients were enrolled, of whom 5 discontinued participation. POUR was diagnosed in 20 of the remaining 95 patients (21.1%). The treatment group contained 48 patients, of whom 6 (12.5%) developed POUR, whereas POUR occurred in the 14 of the 47 patients (29.8%) in the non-treatment group. Tamsulosin treatment reduced the risk of POUR by two-thirds (odds ratio [OR], 0.337; 95% confidence interval [CI], 0.117-0.971; p=0.044). The risk reduction associated with tamsulosin treatment remained robust post-adjustment for potential covariates (OR, 0.250; 95% CI, 0.069-0.905; p=0.038). CONCLUSIONS: Tamsulosin administration immediately after lower limb arthroplasty reduced the incidence of urinary retention and diminished the need for long-term catheterization.

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.

Does preoperative mechanical prophylaxis have additional effectiveness in preventing postoperative venous thromboembolism in elderly patients with hip fracture?-Retrospective case-control study.

BACKGROUND: Elderly patients undergoing hip fracture surgery (HFS) are at increased risk of postoperative venous thromboembolism (VTE). To reduce this risk, combined postoperative mechanical and chemical thromboprophylaxis has been routinely performed after HFS in these patients. This retrospective case-control study was conducted to evaluate the additional effectiveness of preoperative mechanical thromboprophylaxis for the prevention of VTE following HFS in elderly patients. METHODS: Of 539 consecutive patients aged 70 years or older undergoing HFS, 404 (control group) did not receive preoperative mechanical thromboprophylaxis, while 135 (study group) received mechanical thromboprophylaxis using an intermittent pneumatic compression device and graduated compression stockings from the time of admission until surgery. All patients received combined postoperative mechanical and chemical thromboprophylaxis following HFS in accordance with the same protocol. The incidence of symptomatic VTE confirmed based on clinical symptoms and 3-dimensional CT angiography within one month of surgery was investigated in both groups. RESULTS: The American Society of Anesthesiologists grade was higher (p = 0.016) in the study group and more patients in this group had concomitant cardiovascular and neurologic diseases (p = 0.005 and p = 0.009, respectively). In addition, more patients in the study group had received anticoagulant medication preinjury owing to comorbidities (39% vs 28%, p = 0.025). The overall incidences of symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) were 7.4% and 3.7%, and 2.2% and 1.5% in the control and study groups, respectively. According to multiple logistic regression, symptomatic DVT significantly reduced in the study group (OR 0.28, p = 0.042), while there was no significant difference in the incidence of symptomatic PE between the two groups (p = 0.223). CONCLUSIONS: Preoperative mechanical thromboprophylaxis may confer an additional benefit by preventing postoperative VTE without adding more risk of perioperative bleeding in elderly patients with hip fracture.

Greater Trochanteric Reattachment Using the Third-Generation Cable Plate System in Revision Total Hip Arthroplasty.

BACKGROUND: The purpose of the study is to evaluate the radiologic and functional results of greater trochanteric reattachment using the third-generation cable plate system in revision total hip arthroplasty (THA). METHODS: A total of 47 trochanteric fixations (27 men and 18 women; mean age of 60.2 years) using the third-generation cable plate system in revision THA were retrospectively evaluated. The mean follow-up was 80.4 months (range 27-148 months). The osteotomized greater trochanter was reattached using the Cable-Ready system (Zimmer, Warsaw, IN) and the Dall-Miles cable system (Stryker, Mahwah, NJ). The clinical results with Harris hip score, visual analog scale, and radiologic outcomes were evaluated. RESULTS: The mean Harris hip score was improved from 55.7 (range 17-72) preoperatively to 90.8 (range 68-100; P = .001) postoperatively, and the mean pain score was improved from 6.6 (range 3-10) to 2.5 (range 0-6; P = .001), respectively. Nonunion was observed in 6 hips (12.7%). Migration of the osteotomized greater trochanteric fragment (>1 cm) was seen in 8 hips (17.0%). Cable breakage occurred in 13 cases (27.6%). Although 5 cable plate systems were removed, there was no need for reattachment of the greater trochanter in this study. CONCLUSION: This study showed a relatively high incidence of radiologic failure after greater trochanteric reattachment using the cable plate system in revision THA, although reattachments were not required and clinical outcome was relatively satisfactory. Periodic and close observation for the early detection of failure is necessary.

The Evolution of Computer-Assisted Total Hip Arthroplasty and Relevant Applications.

In total hip arthroplasty (THA), the accurate positioning of implants is the key to achieve a good clinical outcome. Computer-assisted orthopaedic surgery (CAOS) has been developed for more accurate positioning of implants during the THA. There are passive, semi-active, and active systems in CAOS for THA. Navigation is a passive system that only provides information and guidance to the surgeon. There are 3 types of navigation: imageless navigation, computed tomography (CT)-based navigation, and fluoroscopy-based navigation. In imageless navigation system, a new method of registration without the need to register the anterior pelvic plane was introduced. CT-based navigation can be efficiently used for pelvic plane reference, the functional pelvic plane in supine which adjusts anterior pelvic plane sagittal tilt for targeting the cup orientation. Robot-assisted system can be either active or semi-active. The active robotic system performs the preparation for implant positioning as programmed preoperatively. It has been used for only femoral implant cavity preparation. Recently, program for cup positioning was additionally developed. Alternatively, for ease of surgeon acceptance, semi-active robot systems are developed. It was initially applied only for cup positioning. However, with the development of enhanced femoral workflows, this system can now be used to position both cup and stem. Though there have been substantial advancements in computer-assisted THA, its use can still be controversial at present due to the steep learning curve, intraoperative technical issues, high cost and etc. However, in the future, CAOS will certainly enable the surgeon to operate more accurately and lead to improved outcomes in THA as the technology continues to evolve rapidly.

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.

Revision Total Hip Arthroplasty Using Imageless Navigation With the Concept of Combined Anteversion.

BACKGROUND: The purpose of the study was to evaluate the implant positions and clinical results of revision total hip arthroplasty (THA) using an imageless navigation with the concept of combined anteversion. METHODS: A total of 40 cementless revision THAs (24 men and 16 women) using an imageless navigation with the concept of combined anteversion were retrospectively evaluated. The concept of combined anteversion was applied in cup positioning based on Widmer's equation (cup anteversion + 0.7 × stem anteversion). The mean follow-up period was 80.7 months. Postoperatively, the inclination of the cup was evaluated on standard anteroposterior view of the radiograph, and the anteversion of the cup and femoral stem was evaluated using computed tomography scan. A cup inclination of 40° ± 10° and combined anteversion of the cup and femoral stem of 37° ± 10° based on Widmer's equation were regarded as the "safe zone." RESULTS: The average anteversion of the revised femoral stems was 15.3° ± 2.9° (range, 9.5°-21.5°), whereas that of the remained femoral stems was 17.4° ± 9.7° (range, 4.2°-29.8°). The inclination, anteversion of the cup, and combined anteversion after revision THA were 42.3° ± 3.1° (range, 32.1°-48.2°), 25.0° ± 2.9° (range, 16.9°-29.5°), and 36.1° ± 3.4° (range, 27.2°-42.9°), respectively. Therefore, the position of the implants, relative to the safe zone, showed no outliers after the revision surgery. Neither dislocation nor osteolysis was observed after the surgery. CONCLUSION: Favorable results of this study indicate that imageless navigation helps the surgeon in placing the components of revision THA in the safe zone. This study also shows that when this safe zone is consistently obtained, then no postoperative dislocations were observed in these patients over the 6-year follow-up period.

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. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 912-926, 2017.

Postoperative fever after hemiarthroplasty in elderly patients over 70 years of age with displaced femoral neck fracture: Necessity of routine workup?

OBJECTIVES: Displaced femoral neck fracture in elderly patients has been treated with hemiarthroplasty as the treatment of choice. Fever following HA is common in these elderly patients. The aim of this study was to determine which post-HA fever workup could be beneficial in this group of patients. METHODS: A total of 272 consecutive patients aged ≥70 years undergoing HA for displaced femoral neck fracture were retrospectively investigated. Postoperative fever (POF) was defined as any recorded body temperature ≥38°C in the early postoperative period. POF in each patient was characterized by the maximum temperature, the day of the first fever, and frequency of fever, stratified as either single or multiple fever spikes. Medical records were reviewed to identify positive fever workups and febrile complications. RESULTS: Of 272 patients, 135 (49.6%) developed POF. A total of 428 routine diagnostic tests were performed in all patients with POF, of which only 57 tests (13.3%) were positive. Urinalysis showed the highest positive rate (21.9%), followed by urine culture (14.3%), chest x-ray (12.6%), and blood culture (1.1%). The most common febrile complication was pneumonia (12.6%), followed by urinary tract infection (8.1%). On multivariate logistic regression for positive workups, only fever after postoperative day (POD) 2 was a risk factor for positive chest x-ray (OR 3.86, p=0.016) and urine culture (OR 5.04, p=0.019). Moreover, fever after POD 2 (OR 6.93, p<0.0001) and multiple fever spikes (OR 2.92, p=0.026) were independent predictors of infectious febrile complications. CONCLUSIONS: Routine workup for POF following hemiarthroplasty in elderly patients with displaced femoral neck fracture is not warranted. However, for fever after POD 2 and multiple fever spikes, chest x-ray and urinalysis would be necessary to rule out the two most common febrile complications such as pneumonia and urinary tract infection.

Torsional malalignment, how much significant in the trochanteric fractures?

OBJECTIVES: The rotational alignment is definitely important in the long bones such as tibias and femurs. We also predict the importance of rotational alignment in the trochanteric fractures. So we measured torsional malalignment in trochanteric fracture and anlaysed their risk factors and their clinical significance. METHODS: A total of 109 inpatients who had undergone internal fixation following trochanteric fracture and a postoperative pelvic CT scan between 2008 and 2013, with at least one year follow-up, were selected. Factors that affect torsional malalignment, such as age, gender, fracture stability, injured area, operative time, time of surgery after admission, and ASA status, were investigated. Factors that affect the patients' clinical results in malrotation, including ambulation time after surgery, postoperative complication rates, pain assessment of VAS one year postoperatively and Koval score, were also investigated. RESULTS: Of the 109 subjects, torsional malalignment was observed in 28 (25.7%) subjects with a mean torsional malalignment angle of 20.7° (range: -31.2° to 27.1°). Torsional malalignment risk factors were fracture stability (p=0.021) and operative time (p=0.043). In terms of the time to ambulation after surgery, the postoperative complication rates, and the VAS and Koval scores at one year postoperatively, no statistically significant difference was observed between the torsional malalignment patients and the non-deformity patients. CONCLUSIONS: In this study, 25.7% of the patients who had undergone internal fixation following trochanteric fracture experienced torsional malalignment. Major factors of the torsional malalignment were an unstable fracture and the consequent delay in the operative time. But the torsional malalignment was deemed to have no effect on clinical results.

Indirect reduction of posterior wall fragment using a suture anchor in acetabular posterior wall fracture with posterior labral root tear.

Posterior wall fractures, which are the most common type of acetabulum fracture, are frequently accompanied with an avulsion tear of the posterior labral root as well as hip dislocation due to the injury mechanism. In the treatment of these fractures with an avulsed posterior labral root attached to posterior wall fragment, the use of a suture anchor can induce indirect reduction of a posterior wall fragment as well as direct repair of a labral root tear simultaneously. We describe the simple and efficient technique using a suture anchor in posterior wall acetabular fractures and surgical outcomes of two cases treated with this technique.

Factors influencing functional outcomes in united intertrochanteric hip fractures: a negative effect of lag screw sliding.

The purpose of this study was to investigate the factors influencing functional outcomes in elderly patients with united intertrochanteric fractures treated with hip nails and to ascertain whether decreased femoral offset due to lag screw sliding has a negative effect on functional outcomes in these patients. This retrospective study included 65 patients older than 65 years with united intertrochanteric fractures treated with hip nails. Functional outcomes were assessed using the Short Form-36 (SF-36) and a visual analog scale (VAS) 6 months postoperatively. Mean patient age was 77.8 years (range, 65-90 years); mean follow-up was 20.7 months (range, 12-38 months). More lag screw sliding occurred as bone mineral density (BMD) decreased. It was also greater in unstable fractures and acceptable reduction status. Less accurate reduction and greater lag screw sliding showed significant negative effects on most subscales of the SF-36, especially Physical Functioning and Role Physical. A significant positive correlation was observed between the extent of lag screw sliding and VAS. Lag screw sliding affected by fracture type, reduction quality, and BMD has a negative effect on functional outcomes in elderly patients with united intertrochanteric fractures. Therefore, the preservation of anatomical femoral offset as much as possible is needed to obtain better functional outcome through the minimization of lag screw sliding by more accurate reduction, which is a controllable factor, especially in osteoporotic unstable intertrochanteric fractures.

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.

Future bearing surfaces in total hip arthroplasty.

One of the most important issues in the modern total hip arthroplasty (THA) is the bearing surface. Extensive research on bearing surfaces is being conducted to seek an ideal bearing surface for THA. The ideal bearing surface for THA should have superior wear characteristics and should be durable, bio-inert, cost-effective, and easy to implant. However, bearing surfaces that are currently being implemented do not completely fulfill these requirements, especially for young individuals for whom implant longevity is paramount. Even though various new bearing surfaces have been investigated, research is still ongoing, and only short-term results have been reported from clinical trials. Future bearing surfaces can be developed in the following ways: (1) change in design, (2) further improvement of polyethylene, (3) surface modification of the metal, (4) improvement in the ceramic, and (5) use of alternative, new materials. One way to reduce wear and impingement in THA is to make changes in its design by using a large femoral head, a monobloc metal shell with preassembled ceramic liner, dual mobility cups, a combination of different bearing surfaces, etc. Polyethylene has improved over time with the development of highly crosslinked polyethylene. Further improvements can be made by reinforcing it with vitamin E or multiwalled carbon nanotubes and by performing a surface modification with a biomembrane. Surface modifications with titanium nitride or titanium niobium nitride are implemented to try to improve the metal bearings. The advance to the fourth generation ceramics has shown relatively promising results, even in young patients. Nevertheless, further improvement is required to reduce fragility and squeaking. Alternative materials like diamond coatings on surfaces, carbon based composite materials, oxidized zirconium, silicon nitride, and sapphire are being sought. However, long-term studies are necessary to confirm the efficacy of these surfaces after enhancements have been made with regard to fixation technique and implant quality.

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 Poisson's 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, Poisson's 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 Poisson's ratio despite misalignment between specimens and experimental devices. In this study, Poisson's 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 Poisson's 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.

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.

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.