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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

One-day antibiotic infusion for the prevention of postoperative infection following arthroplasty: a case control study.

Intravenous antibiotics effectively reduce the prevalence of postoperative infection. However, Japanese orthopaedic surgeons have no consensus with regard to the optimal duration of prophylaxis. The aim of this study is to compare the outcome of one-day intravenous antibiotic administration with that of long-term intravenous antibiotic administration. Patients who underwent total hip or knee arthroplasty were divided into 2 groups to receive one of 2 prophylactic protocols retrospectively. Group A (223 patients) received intravenous antibiotics twice only on the day of surgery, whereas Group B (104 patients) received intravenous antibiotics for at least 3 days after surgery. We analyzed the wound infection rate and monitored liver and renal functions. None of these patients had a postoperative infection. No liver dysfunction and renal dysfunction were observed. One-day antibiotic infusion was as effective as long-term antibiotics in preventing infection after arthroplasty and achieved greater cost effectiveness.

Retrospective analysis of metastatic sarcoma patients.

Numerous studies have reported the survival of metastatic sarcoma patients who have undergone either a lung metastasectomy or chemotherapy. However, little is known with regards to the clinical course of patients with bone or soft tissue sarcomas who have succumbed to disease. This study aimed to analyze the metastatic patterns of sarcoma patients and to describe the clinical course after the detection of distant metastasis. We reviewed the clinical records of 255 patients with a diagnosis of sarcoma who were referred to our institution, and found 63 patients who succumbed due to metastasis. We examined the clinical features of the initially detected distant metastases, the subsequent clinical course up to the time of patient death and the survival time of patients who died of lung metastasis. Of the 63 patients who died of distant metastasis, 52 (83%) developed lung metastasis as the first metastatic site, while 22 (35%) developed extra-pulmonary metastasis. The majority (77%; 49 of 63 patients) died of primary metastasis. While all 18 bone sarcoma patients died of lung metastasis, 11 of the 45 soft tissue sarcoma patients died of extra-pulmonary metastasis. Six patients died of brain metastasis. The survival of the patients with lung metastasis was only approximately 6 months following the cessation of treatment, regardless of the type of treatment used. These results indicate that planned follow-up and treatment of sarcomas require a precise knowledge of tumor clinical behavior, particularly of the preponderant activity.

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.

Incidence and time course of asymptomatic deep vein thrombosis with fondaparinux in patients undergoing total joint arthroplasty.

INTRODUCTION: There are many reports concerning fondaparinux prophylaxis of asymptomatic deep vein thrombosis (DVT) after total hip arthroplasty (THA) or total knee arthroplasty (TKA), but little is known about the time course of aymptomatic DVT development during the administration of fondaparinux. The aim of the present study was to define the incidence and time course of aymptomatic DVT development during administration of fondaparinux, and to assess the efficacy of fondaparinux in resolving DVT. MATERIALS AND METHODS: We studied consecutive 71 patients who underwent THA surgery, and 30 patients who underwent TKA surgery with fondaparinux prophylaxis. Patients received once-daily subcutaneous injections of 2.5mg of fondaparinux for 14 days after surgery. DVT was diagnosed by ultrasonography, and it was scheduled on the day of surgery on day 1, day 4, and day 14 after surgery. RESULTS: In patients who received fondaparinux for 14 days after THA surgery, the incidence of DVT was 0% on the day of the surgery, 13.6% at day 1, 27.1% at day 4, and 11.9% at day 14. In patients who received fondaparinux for 14 days after TKA surgery, the incidence of DVT was 4.2% on the day after surgery, 50.0% at day 1, 58.3% at day 4, and 20.8% at day 14. The incidence of DVT after THA or TKA surgery at day 14 was significantly reduced compared to that at day 4. CONCLUSION: The incidence of asymptomatic DVT up to day 4 was high, but with 14 days continued treatment of fondaparinux, the incidence of asymptomatic DVT occurring at postoperative day 4 was significantly reduced at day 14.