The risk factor of preoperative deep vein thrombosis in patients undergoing total knee arthroplasty.

OBJECTIVES: The objective of this retrospective study was to investigate the prevalence of asymptomatic deep vein thrombosis (DVT) and the risk of DVT in patients admitted to hospital for total knee arthroplasty (TKA). METHODS: From September of 2003 to December of 2013, 322 patients admitted for TKA were eligible for this retrospective study. A diagnosis of DVT was confirmed by Doppler ultrasonography. The prevalence of silent DVT in the lower limbs in patients before TKA was assessed. The risk factors for preoperative DVT were investigated, as well as the correlation of DVT in the patient's background and medical history. RESULTS: Preoperative DVT was diagnosed in 56 patients (17.4%) including 3 patients with proximal DVT. Significantly elevated risks of DVT were found in patients undergoing revision TKA (p < 0.01), patients with rheumatoid arthritis (RA) (p < 0.005), patients with connective tissue diseases (CTDs) (p < 0.05), and female patients (p < 0.05) on univariate analyses. Multiple linear regression analysis showed that RA, CTDs and admission for revision TKA were independent risk factors for preoperative DVT. CONCLUSIONS: A high prevalence of preoperative DVT was found in patients admitted to hospital for TKA. Admission to the hospital for RA, CTDs and revision TKA were risk factors for preoperative DVT.

The Relationship of BMD Increases Between the First 12 Months and the Latter 12 Months by Daily Teriparatide Treatment.

The degree of correlation between the first 12 months and the latter 12 months of increased bone mineral density (BMD) with teriparatide treatment is unknown. We retrospectively investigated the correlation between the first 12 months and the latter 12 months of increased BMD owing to teriparatide treatment. We retrospectively analyzed 357 patients (mean age, 78 years) with osteoporosis treated with teriparatide 20 µg/day for 24 months. The primary efficacy measure was the correlation between lumbar spine (LS) and femoral neck (FN) BMD increases from baseline to 12 months and from 12 to 24 months. The correlation between the first 12 months and the latter 12 months of increased BMD was evaluated. We investigated the correlation between the increases in BMD and the baseline procollagen type I N-terminal propeptide (PINP) concentration. LS BMD significantly increased by 9.7 ± 8.3 % in the first 12 months and 3.5 ± 4.8 % in the latter 12 months. FN BMD increased by 2.2 ± 8.4 % in the first 12 months and 1.3 ± 4.9 % in the latter 12 months. Increased LS and FN BMD were not significantly correlated between the first 12 months and the latter 12 months. The serum baseline PINP concentration was correlated with the LS BMD in the first 12 months, and similarly, the PINP concentration at 12 months was correlated with the latter 12 months of increased LS BMD. Increased BMD by teriparatide treatment in the first 12 months and the latter 12 months was not significantly correlated.

Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors.

BACKGROUND: Neural-cadherin (N-cadherin) is one of the most important molecules involved in tissue morphogenesis, wound healing, and the maintenance of tissue integrity. Recently, the cleavage of N-cadherin has become a focus of attention in the field of cancer biology. Cadherin and their ectodomain proteolytic shedding play important roles during cancer progression. The aims of this study are to investigate the serum soluble N-cadherin (sN-CAD) levels in patients with malignant bone and soft tissue tumors, and to evaluate the prognostic significance of the sN-CAD levels. METHODS: We examined the level of serum sN-CAD using an ELISA in 80 malignant bone and soft tissue tumors (bone sarcoma, n = 23; soft tissue sarcoma, n = 50; metastatic cancer, n = 7) and 87 normal controls. The mean age of the patients was 51 years (range, 10-85 years) and the mean follow-up period was 43 months (range, 1-115 months). RESULTS: The median serum sN-CAD level was 1,267 ng/ml (range, 135-2,860 ng/ml) in all patients. The mean serum sN-CAD level was 1,269 ng/ml (range, 360-2,860 ng/ml) in sarcoma patients, otherwise 1,246 ng/ml (range, 135-2,140 ng/ml) in cancer patients. The sN-CAD levels in patient were higher than those found in the controls, who had a median serum level of 108 ng/ml (range, 0-540 ng/ml). The patients with tumors larger than 5 cm had higher serum sN-CAD levels than the patients with tumors smaller than 5 cm. The histological grade in the patients with higher serum sN-CAD levels was higher than that in the patients with lower serum sN-CAD levels. A univariate analysis demonstrated that the patients with higher serum sN-CAD levels showed a worse disease-free survival rate, local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate compared to those with lower serum sN-CAD levels. In the multivariate analysis, sN-CAD was an independent factor predicting disease-free survival. CONCLUSIONS: sN-CAD is a biomarker for malignant bone and soft tissue tumors, and a potentially valuable pre-therapeutic prognostic factor in patients with bone and soft tissue sarcoma.

Failure mechanism of a constrained liner: a case report.

Instability after primary and revision total hip arthroplasty continues to be a problem. The use of a constrained system helps manage this problem. A new constrained total hip arthroplasty, Trilogy constrained liner (Zimmer, Warsaw, IN), is currently in use. We report a case showing dislocation following a Trilogy constrained total hip arthroplasty. In this case, when an impingement between the femoral neck and the anterior part of the polyethylene liner occurred, the hip dislocated easily although both polyethylene and reinforcing ring were properly positioned. The lever-out test showed that the Trilogy constrained liner is safe and compares favourably with other implants. Surgeons should be aware that constrained acetabular systems are not infallible and they should pay attention to place implants in good position even when constrained THA is performed.

Platelet-Rich Plasma Releasate versus Corticosteroid for the Treatment of Discogenic Low Back Pain: A Double-Blind Randomized Controlled Trial.

Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. Sixteen patients with discogenic LBP received an intradiscal injection of either autologous PRPr or corticosteroid (CS). Patients in both groups who wished to have PRPr treatment received an optional injection of PRPr eight weeks later. The primary outcome was change in VAS from baseline at eight weeks. Secondary outcomes were pain, disability, quality of life (QOL), image analyses of disc degeneration, and safety for up to 60 weeks. The VAS change at eight weeks did not significantly differ between the two groups. Fifteen patients received the optional injection. Compared to the CS group, the PRPr group had a significantly improved disability score at 26 weeks and walking ability scores at four and eight weeks. Radiographic disc height and MRI grading score were unchanged from baseline. PRPr caused no clinically important adverse events. PRPr injection showed clinically significant improvements in LBP intensity equal to that of CS. PRPr treatment relieved pain, and improved disability and QOL during 60 weeks of observation.

The cleavage of N-cadherin is essential for chondrocyte differentiation.

The aggregation of chondroprogenitor mesenchymal cells into precartilage condensation represents one of the earliest events in chondrogenesis. N-cadherin is a key cell adhesion molecule implicated in chondrogenic differentiation. Recently, ADAM10-mediated cleavage of N-cadherin has been reported to play an important role in cell adhesion, migration, development and signaling. However, the significance of N-cadherin cleavage in chondrocyte differentiation has not been determined. In the present study, we found that the protein turnover of N-cadherin is accelerated during the early phase of chondrogenic differentiation in ATDC5 cells. Therefore, we generated the subclones of ATDC5 cells overexpressing wild-type N-cadherin, and two types of subclones overexpressing a cleavage-defective N-cadherin mutant, and examined the response of these cells to insulin stimulation. The ATDC5 cells overexpressing cleavage-defective mutants severely prevented the formation of cartilage aggregates, proteoglycan production and the induction of chondrocyte marker gene expression, such as type II collagen, aggrecan and type X collagen. These results suggested that the cleavage of N-cadherin is essential for chondrocyte differentiation.

Evaluation of soluble fibrin and D-dimer in the diagnosis of postoperative deep vein thrombosis.

Soluble fibrin (SF) and D-dimer are useful for making the diagnosis of deep vein thrombosis (DVT). However, the evidence for using such markers and optimal timing to diagnose postoperative DVT are unclear. We evaluate the usefulness of SF and D-dimer testing for the diagnosis of postoperative DVT. A total of 207 patients who had total hip arthroplasty or knee arthroplasty were evaluated. SF and D-dimer were tested on postoperative days 1 and 7. DVT was confirmed with ultrasonography. SF level on postoperative day 1 was the most useful, although D-dimer evaluation on postoperative days 1 and 7 was also useful. Using a SF cut-off of more than 4.00 microg ml(-1), the sensitivity was 90%, the specificity was 33%. Although the SF and D-dimer tests cannot be used as stand-alone tests, SF and D-dimer are valuable screening tools. We recommend two-stage screening including first with the SF or D-dimer test, followed by ultrasonography or venography.

Second rebound-associated vertebral fractures after denosumab discontinuation.

Here, we report the case of a 69-year-old female who discontinued denosumab to undergo dental treatment. She subsequently suffered rebound-associated vertebral fractures (RVFs) twice. Denosumab is approved in several countries for osteoporosis treatment. Its discontinuation can result in bone turnover rebound increase and rapid bone mineral density loss. Rebound-associated vertebral fractures (RVFs) after discontinuing denosumab have been widely reported. We previously reported the case of a patient who suffered RVFs after discontinuing denosumab to undergo dental treatment. A 69-year-old female suffered five acute VFs 10 months after the last denosumab injection. The current report identifies the risks associated with denosumab discontinuation to undergo dental treatment. The patient described in this report also underwent an additional clinical course after the first RVFs. Next month after the first RVFs, she developed severe back pain when she changed her posture. Magnetic resonance imaging showed new RVFs at T9 and T12 levels. This case indicates that RVFs may occur more than once. In addition, it suggests that additional denosumab injections do not completely eliminate the risk of RVFs.

Usefulness of limb salvage surgery for bone and soft tissue sarcomas of the distal lower leg.

PURPOSE: The usefulness of limb salvage surgery for distal lower leg sarcoma remains controversial. We analyzed the long-term prognosis, limb function, and complications after limb salvage treatment of patients with distal lower leg sarcoma. METHODS: Ten patients treated with limb salvage surgery for primary distal lower leg sarcoma were retrospectively reviewed. The median follow-up period after the first operation was 9.0 years. We performed three types of reconstructive techniques for the skeletal defect after a wide resection, including (1) arthrodesis with a combination of autograft and intraoperative autoclaved tumor bone graft in two patients, or allograft in one patient, (2) ankle joint preserving surgery using intraoperative extracorporeal irradiated tumor bone graft in five patients, and (3) prosthesis in two patients. RESULTS: The overall survival rate was 80%. The 5-year disease-free survival was 80%. The rate of limb preservation at the final follow-up was 90%. The mean functional score according to the scoring system of the Musculoskeletal Tumor Society was 88% at the final follow-up. Postoperative complications occurred in seven patients. Skin trouble occurred in three patients, infectious non-union in one patient, fracture in three patients, and loosening of prosthesis in one patient. CONCLUSIONS: Despite the high rate of complications, patients treated with limb salvage surgery for the distal lower leg sarcoma revealed excellent final functional results without impairing the oncologic results. Limb salvage surgery is therefore considered to be an effective treatment option for distal lower leg sarcoma when adequate informed consent can be obtained from the patient.

Primary osteosarcoma of the lung: a case report and review of the literature.

Primary osteosarcoma of the lung is exceedingly rare. A 72-year-old man was admitted to our hospital; a primary osteosarcoma of the lung was diagnosed following computed tomography-guided needle biopsy. He died of rapidly progressing respiratory insufficiency without effective treatment seven months after the onset of symptoms. Macroscopic findings at autopsy showed typical histologic features of osteosarcoma without any bony lesion. Here we present a rare case and review the clinicopathological features of 20 previously reported cases.

Course of avascular necrosis of femoral head without collapse of femoral head at first examination: minimum 8-year follow-up.

Disruption of the femoral head contour by collapse of necrotic segments is considered to be an important turning point in the history of avascular necrosis of the femoral head, and in many cases, surgical treatment is required soon after the onset of symptoms. However, in a few cases, conservative treatment is sufficiently effective to avoid surgical procedures for long periods. For patients with early-stage avascular necrosis, it is important to accurately predict its natural course. This article documents the characteristics of patients who can be treated without surgery for long periods. Seventeen hips in 13 patients with avascular necrosis of the femoral head without collapse of the femoral head at first examination were followed for at least 8 years of conservative treatment. Long-term outcomes of hips with avascular necrosis were divided into 3 groups: (1) hips without collapse, (2) hips with progression but cessation of collapse, and (3) hips with progression of collapse. In groups 1 and 2, good clinical results are expected. Hips with femoral head collapse .3 mm at 3 years from the onset of hip pain progressed to osteoarthritis. Our analysis indicated that collapse of the femoral head does not necessarily indicate a poor prognosis, and even after collapse occurs, subsequent cessation of collapse can be expected in a certain percentage of hips.

Efficacy of Switching From Teriparatide to Bisphosphonate or Denosumab: A Prospective, Randomized, Open-Label Trial.

There is no consensus on an optimal treatment after daily teriparatide (TPTD). We performed a prospective, randomized, open-label, 12-month trial to investigate the efficacy of follow-up treatment after daily TPTD treatment for Japanese patients. Three-hundred patients were enrolled in this study. Patients received oral bisphosphonate (BP) including alendronate (ALN; 35 mg/week) and minodoronate (MINO; 50 mg/month), or subcutaneous denosumab (60 mg/6 month). The primary efficacy measure was bone mineral density (BMD) responses in the lumbar spine (LS) and femoral neck (FN). Lumbar spine BMD increased by 1.3 ± 5.1% in the ALN subgroups, 0.5 ± 4.6% in the MINO subgroups, and 4.3 ± 3.5% in the denosumab subgroups. Femoral neck BMD increased by 0.7 ± 4.6% in the ALN subgroups, 0.2 ± 4.6% in the MINO subgroups, and 1.4 ± 3.4% in the denosumab subgroups. Lumbar spine BMD increases were significantly greater in the denosumab subgroup than the BP subgroups. There were no significant differences in FN BMD increases among the three subgroups. Lumbar spine BMD increases were significantly greater in the denosumab subgroup than the BP subgroups, whereas FN BMD increases were not significant. Denosumab treatment was more effective in increasing BMD and therefore has the potential benefit of fracture prevention. Further research is warranted to determine the optimal treatment after daily TPTD. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Efficacy of Daily Teriparatide Treatment in Low Levels of Walking State Patients.

INTRODUCTION: Little is known about the efficacy of osteoporosis medication in patients with low levels of walking state, namely, influence by immobilization levels. We retrospectively compared the efficacy of the daily teriparatide therapy in patients with low and high levels of walking state to detect possible immobilization-related differences. METHODS: We analyzed 661 patients treated with 20 µg/day of teriparatide for 24 months. We measured the changes in the bone mineral density (BMD) of the lumbar spine (LS) and of the femoral neck (FN), the changes in serum procollagen type I N-terminal propeptide (PINP) levels and urinary N-telopeptide (uNTX) excretion. To compare the results of BMD and bone turnover marker, the patients were divided into two subgroups, low levels of walking state and high levels of walking state. RESULTS: Compared with baseline, in the low levels of walking state subgroup, the percent LS BMD and FN BMD increased significantly by 12.8 ± 8.9% and 5.0 ± 13.8% at 24 months, respectively (p < 0.01 vs baseline for LS and FN, respectively); the mean absolute LS BMD and FN BMD change was 0.101 ± 0.067 g/cm2 and 0.017 ± 0.063 g/cm2 at 24 months, respectively. In the high levels of walking state subgroup, the percent LS BMD and FN BMD increased significantly by 13.4 ± 9.5% and 3.1 ± 7.8% at 24 months, respectively; the mean absolute LS BMD and FN BMD change was 0.104 ± 0.068 g/cm2 and 0.017 ± 0.042 g/cm2 at 24 months, respectively. The increases in percent and absolute BMD in LS and FN, and the changes in PINP and uNTX were similar between the subgroups. CONCLUSIONS: The efficacy of the daily teriparatide treatment is similar between low levels of walking state patients and high levels of walking state patients and was not influenced by immobilization levels.

Clinical analysis of preoperative deep vein thrombosis risk factors in patients undergoing total hip arthroplasty.

OBJECTIVES: The objective of this retrospective study was to investigate the risk of deep vein thrombosis (DVT) in patients admitted to hospital for total hip arthroplasty (THA). METHODS: From September of 2003 to December of 2010, 505 patients admitted for THA were eligible for the retrospective study. The diagnosis of preoperative DVT, which was based on previous venous thromboembolism (VTE) management studies, was confirmed by Doppler ultrasonography. The prevalence of silent DVT in lower limbs in patients before THA was assessed. And the risk factors for preoperative DVT were investigated the correlation of DVT in the patient's background and medical history. RESULTS: Preoperative DVT was diagnosed in 62 of 505 (12.3%) patients overall. Significantly elevated risks of DVT were found in patients with increased age, a history of major surgery, revision THA, rheumatoid arthritis (RA), and a history of cancer treatment. Multiple linear regression analysis showed that increased age, RA, and history of major surgery were the independent risk factors for preoperative DVT in this study. CONCLUSIONS: A high prevalence (12.3%) of preoperative DVT was found in patients admitted to hospital for THA. Patients with increased age, RA, and a history of major surgery may be at an increased risk of preoperative DVT. The present results suggest that instrumental screening should be encouraged, at least in subgroups at higher risk of preoperative DVT.

Cortical thickness of the femur and long-term bisphosphonate use.

Femoral cortical thickening has been mentioned in reports of atypical subtrochanteric/femoral shaft (ST/FS) fractures, which are associated with long-term bisphosphonate (BP) use. However, whether thickening precedes BP use or results from BP use, as well as the role BPs may play in cortical thickening remain unclear. The purpose of this study was to investigate the relationship between cortical thickness and BP use. We enrolled 142 patients (mean age 79 years) who had taken BPs for more than 5 years, and enrolled 426 osteoporosis patients who had not used BPs as controls. We performed a case-control study of patients with long-term BP use and controls matched for age, sex, and levels of activities of daily living (ADLs) (1:3 ratio). On femoral radiographs, we measured femoral cortical thickness in three regions: 5 cm and 12.5 cm below the lesser trochanter and in the region of maximal cortical thickness. We compared cortical thicknesses between patients taking BP and controls and evaluated longitudinal changes in cortical thickness. There were no significant differences in cortical thickness between long-term BP users and controls. In addition, after further use of BP for a minimum of 1 year, we observed no significant differences in the changes in cortical thickness at any level of the femur. In conclusion, our study did not find evidence of cortical thickening at the ST/FS area of the femur with long-term BP use.

Determinants associated with bone mineral density increase in response to daily teriparatide treatment in patients with osteoporosis.

INTRODUCTION: Several factors associated with bone mineral density (BMD) increase are reported with daily teriparatide treatment, but there has been no systematic analysis to summarize these associations. The purpose of this study was to investigate the clinical determinants associated with BMD increase to daily teriparatide treatment. METHODS: This was a retrospective study. We performed an analysis of 306 patients diagnosed with osteoporosis. Teriparatide was administered at 20µg/day for 12months. The primary efficacy measure was a change in lumbar spine (LS) BMD from baseline at 12months. To determine the response variables of BMD changes, we investigated the clinical determinants using univariate and multivariate analyses. RESULTS: There was a 9.8±8.2% increase in LS BMD after 12months. Prior bisphosphonate treatment and baseline procollagen type I N-terminal propeptide (PINP) concentration were significantly associated with LS BMD absolute response by univariate analyses. In the multiple regression model, patients with higher baseline PINP concentration had a significantly greater LS BMD absolute increase. Prior bisphosphonate use lost its correlation in the multiple regression models. CONCLUSION: Our results showed that baseline PINP concentration was a useful predictor of LS BMD absolute increase regardless of prior treatment.

Prognostic significance of CD155 mRNA expression in soft tissue sarcomas.

CD155 was initially identified as a receptor for poliovirus. Several studies have demonstrated that CD155 overexpression in cancer cells is significant in their migration, invasion, proliferation and metastasis. The objective of the present study was to investigate the correlation between CD155 expression and the clinical aggressiveness of soft tissue tumors. The CD155 expression levels in 43 surgically-resected soft tissue tumors were evaluated using the quantitative real-time polymerase chain reaction (PCR). The clinicopathogical factors affecting the expression levels of CD155 mRNA were investigated and the association between the expression levels of CD155 and patient prognosis was identified. The CD155 expression level was not correlated with the patient gender, site of the primary tumor, tumor depth, tumor size or presence of distant metastasis at presentation, but was correlated with patient age (Fisher's exact test). The local recurrence-free survival rate for patients with a high CD155 expression level was observed to be significantly poorer compared with that of patients with low CD155 expression levels (P=0.0401). Moreover, a multivariate analysis indicated that a high CD155 expression level was an independent adverse prognostic factor for local recurrence-free survival (hazard ratio, 6.369; P=0.0328). The present study therefore suggests that the expression level of CD155 is a useful marker for predicting the local recurrence of soft tissue tumors.

Ewing's sarcoma with an uncommon clinical course: A case report.

Here, a case of Ewing's sarcoma family of tumors (ESFT) of the femur with an unusual clinical course is reported. At 20 years of age, the patient had undergone curettage of a bone tumor of the right femur which was diagnosed as ESFT. One cycle of chemotherapy with vincristine and cyclophosphamide and radiotherapy for a total dose of 40 Gy was administered. The patient did not develop any recurrence or metastases for the following 18 years, in spite of the inadequacy of the initial treatment. At 38 years of age, he was referred to our institution with right thigh pain that had persisted for several months. Radiographs and magnetic resonance imaging findings showed a mass lesion in his proximal femur extending to the soft tissue. An open biopsy was performed and the lesion was diagnosed as recurrence of ESFT, although a molecular biological investigation did not reveal any expression of the characteristic fusion genes that have previously been reported. The patient received standard multimodal therapy employing standard combination chemo-therapy for ESFT and wide surgical excision. The patient has been disease-free for 9 years since the treatment. This patient may have a rare subtype of ESFT with an unknown chromosomal translocation and relatively non-aggressive biological behavior.

Prosthetic limb salvage surgery for bone and soft tissue tumors around the knee.

In this study, we analyzed long-term survival, limb function and associated complications after prosthetic limb salvage treatment in patients with bone and soft tissue tumors around the knee joint. A total of 63 patients treated with prosthetic limb salvage surgery around the knee were reviewed. The bone tumors involved the distal femur in 45 patients, the proximal tibia in 14 patients and the soft tissue tumors of the proximal lower leg in 4 patients. The median follow-up period after the first operation was 8.0 years. The medical records of the patients, surgical reports, radiographs and histological specimens were retrospectively reviewed. The 5-year overall survival rate was 63.2% in the patients with distal femur tumors and 86.2% in those with tumors of the proximal lower leg. The 5­year prosthetic survival rate was 72.8% in the distal femur and 74.6% in the proximal lower leg. The mean functional score according to the scoring system of the Musculoskeletal Tumor Society (MSTS) was 81% in the patients with distal femur tumors and 82% in the patients with proximal lower leg tumors. Post-operative complications occurred in 27 patients. Limb salvage surgery is considered to be an effective treatment option. However, the high complication rate is a major concern for prosthetic replacement. Future improvements of prostheses are very important.

Oncolytic virotherapy for human bone and soft tissue sarcomas using live attenuated poliovirus.

The poliovirus receptor CD155, is essential for poliovirus to infect and induce death in neural cells. Recently, CD155 has been shown to be selectively expressed on certain types of tumor cells originating from the neural crest, including malignant glioma and neuroblastoma. However, the expression pattern of CD155 in soft tissue sarcoma has not been examined. Therefore, we first examined CD155 expression in sarcoma cell lines, and found the expression of both CD155 mRNA and protein in 12 soft and bone tissue sarcoma cell lines. Furthermore, we examined the effect of live attenuated poliovirus (LAPV) on 6 bone and soft tissue sarcoma cell lines in vitro, and found that LAPV induced apoptosis by activating caspases 7 and 3 in all of these cell lines. Furthermore, in BALB/c nu/nu mice xenotransplanted with HT1080 fibrosarcoma cells, administration of live attenuated poliovirus caused growth suppression of the tumors. These results suggest that oncolytic therapy using a LAPV may represent a new option for the treatment of bone and soft tissue sarcomas.