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Study Design Multicenter prospective study.Objective The influence of central sensitization (CS) on neurological symptoms and surgical outcomes in patients with degenerative cervical myelopathy (DCM) remains unknown. This study aimed to investigate the effects of preoperative CS on surgical outcomes of patients with DCM following posterior decompression surgery.Methods 77 consecutive patients with DCM (mean age 67.1) who received posterior decompression surgery were included in this study. The participants completed CS inventory (CSI) scores and the following patient-reported outcome measures (PROMs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for cervical myelopathy and JOA cervical myelopathy evaluation questionnaire (JOACMEQ) for cervical spinal diseases. The association of preoperative CSI scores with preoperative and postoperative PROMs was analyzed, and their changes were statistically evaluated.Results The preoperative CSI score was significantly decreased at 12 months postoperatively, and it was significantly associated with the JOA score and JOACMEQ preoperatively and at 12 months postoperatively. However, no significant association was observed between preoperative CSI and the postoperative change of any PROMs at 12 months. The posterior decompression surgery significantly improved the JOA scores and ‘lower extremity function’ and ‘quality of life (QOL)’ domains of the JOACMEQ, independent of the severity of preoperative CSI score. Multiple regression analysis demonstrated that preoperative CSI was significantly associated with the ‘QOL’ domain of JOACMEQ and original JOA score at 12 months postoperatively.Conclusion The CSI score can be an auxiliary indicator of surgical outcomes of patients with DCM following posterior decompression surgery.

Study Design This study is a retrospective review.Objective Central sensitization (CS) is a neurological phenomenon that involves hypersensitivity of the central nervous system. The central sensitization inventory (CSI) was developed as a screening tool to assess CS-related symptoms. The purpose of this study was to evaluate the association of preoperative CSI scores with patient-reported outcome measures (PROMs) including neurological symptoms for patients who underwent spine surgeries in a multicenter study.Methods A consecutive 673 patients who underwent spine surgery at 8 different institutions were included in this study. Preoperative CSI scores were assessed for all subjects. The participants completed the following PROMs: the Oswestry Disability Index (ODI), the Japanese Orthopaedic Association (JOA) back pain evaluation questionnaire (JOABPEQ) for lumbar spinal diseases, and the JOA cervical myelopathy evaluation questionnaire (JOACMEQ) for cervical spinal diseases. The association of CSI scores with PROMs was statistically evaluated.Results The average CSI score for the total subjects was 23.6 ± 13.5. The subjects with CS-related symptoms (CSI ≥ 40) were 13.2% (n = 89). The CSI score showed a significant and weak-to-moderate correlation with the PROMs including neurological symptoms that included all the domains of the JOACMEQ for cervical spinal diseases, and JOABPEQ and ODI for lumbar spinal diseases. Among these, psychological factors had the most influence on the correlation with CSI score.Conclusion Central sensitization evaluated by the CSI is related to neurological symptoms and health-related quality of life in patients undergoing elective spine surgery.

AimsPatients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry.MethodsData from 2006 to 2016 was obtained from the BSTT registry. Only patients with STS of the limb were included in the study. Patients with distant metastasis at the initial presentation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study.ResultsA total of 4,483 patients with STS of the limb were identified before propensity score matching. There were 355 patients who underwent UE and 4,128 patients who underwent PE. The five-year disease-specific survival (DSS) rate was significantly better in the patients who received additional excision after UE than in those who underwent PE. There was no significant difference in local recurrence-free survival (LRFS) between the two groups. After propensity score matching, a new cohort of 355 patients was created for both PE and UE groups, in which baseline covariates were appropriately balanced. Reconstruction after tumour excision was frequently performed in patients who underwent additional excision after UE. There were no significant differences in DSS and LRFS between the patients who underwent PE and those who had an additional excision after UE.ConclusionUsing propensity score matching, patients with STS of the limb who underwent additional excision after UE did not experience higher mortality and local failure than those who underwent PE. Reconstruction may be necessary when additional excision is performed.Cite this article: Bone Joint J2021;103-B(12):1809–1814.

Objective TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model.Design Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitrostudy was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction.Results There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor.Conclusion We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.

Pazopanib, a targeted molecular drug, has been proposed as an effective treatment for soft tissue tumour and as a novel adjuvant therapy. There has been a paradoxical concern that wound healing could be inhibited by its anti-angiogenic properties, especially in reconstructive surgery. This paper reports on a 28-year-old woman who underwent flap surgery due to a skin and soft tissue injury after an effective treatment with pazopanib for refractory epithelioid sarcoma. The flap survived without any complication in off-periods of pazopanib for four weeks before and after the surgery, although it is only recommended that the washout periods of pazopanib commence at least seven days before scheduled surgery.

Study Design Multicenter prospective study.Objective Patients with central sensitization (CS) are reported to be at high risk of poor outcomes after spinal surgery. However, the influence of CS on surgical outcomes for lumbar disc herniation (LDH) remains unknown. This study aimed to examine the association between preoperative CS and surgical outcomes in LDH patients.Methods A total of 100 consecutive patients with LDH (mean age 51.2) who underwent lumbar surgery were included in this study. The extent of CS was evaluated using the central sensitization inventory (CSI), a screening tool for CS-related symptoms. The patients completed the following CSI and clinical outcome assessments (COAs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for back pain, JOA back pain evaluation questionnaire (JOABPEQ), and Oswestry Disability Index (ODI). The association between preoperative CSI scores, and preoperative and postoperative COAs was analyzed, and the postoperative changes were statistically evaluated.Results The preoperative CSI score significantly decreased 12 months postoperatively. Preoperative CSI scores showed a significant correlation with most COAs; however, a significant correlation was only identified in the social function and mental health domains of JOABPEC postoperatively. Higher preoperative CSI showed worse preoperative COAs; however, all COAs significantly improved regardless of CSI severity. There were no significant differences in any COAs among the CSI severity groups 12 months postoperatively.Conclusions The results of this study showed that lumbar surgeries significantly improved the COAs regardless of preoperative severity of CS in patients with LDH.

The purpose of this study was to evaluate the mid-term clinical results and polyethylene wear of vitamin E-diffused highly cross-linked polyethylene (HXLPE) and 2-methacryloyloxyethyl phosphorylcholine (MPC)-grafted HXLPE in cementless total hip arthroplasty (THA). Thirty-four THAs with vitamin E-diffused HXLPE (VEPE) and 32-mm cobalt-chromium head, and 116 THAs with MPC-grafted HXLPE and 32-mm alumina head were evaluated. The Merle d’Aubigné and Postel scores were administered. Kaplan–Meier survivorship was analyzed. Annual radiographs were analyzed using computerized method and linear steady-state wear rate was measured. The mean duration of follow-up was 9 years (range, 7–11 years) in VEPE group and 8 years (range, 7–10 years) in MPC group. The mean Merle d’Aubigné and Postel scores improved postoperatively in both groups. Kaplan–Meier survivorship with endpoint of revision was 100% (95% confidence interval, 100%–100%) in VEPE group and 98.3% (95% confidence interval, 93.4%–99.6%) in MPC group at 10 years (P = .44). The mean steady-state wear rate was 0.007 mm/year in VEPE group and 0.006 mm/year in MPC group (P = .60). The clinical results of both groups were good and wear rates of both liners were very low.

Background: Intradiscal condoliase injection is an alternative therapeutic option for lumbar disc herniation (LDH). However, it is often associated with disc degeneration. Several in vivo studies have demonstrated the regenerative potential of platelet-rich plasma (PRP) in disc degeneration. Thus, we hypothesized that the intradiscal injection of PRP releasate (PRPr), a soluble releasate isolated from PRP, has the potential to regenerate degenerated intervertebral discs (IVDs) induced by condoliase. This study examined the regenerative effects of PRPr on rabbit IVDs degenerated following condoliase injection. Methods: Eleven New Zealand white rabbits were used in this study. Condoliase (12.5 mU/10 μl) was injected into two non-contiguous discs (L2-L3 and L4-L5), and L3-L4 disc was left intact as a non-injection control. Saline (20 μl) or PRPr (20 μl) was randomly injected into L2-L3 and L4-L5 discs 4 weeks after the condoliase injection. Disc height (DH) was radiographically monitored biweekly from the day of condoliase injection to 16 weeks post-injection. Changes in DH were expressed as percentage DH (%DH) normalized to the baseline DH. Sixteen weeks after condoliase injection, all rabbits were euthanized, and subjected to MRI and histological analyses. Results: Intradiscal injection of condoliase induced a significant decrease in %DH (L2-L3 and L4-L5) to 52.0% at week 4. However, the %DH began to return to normal after saline injection and reached 76.3% at week 16. In the PRPr group, %DH began to recover to normal after the PRPr injection and was restored to 95.5% at week 16. The MRI-modified Pfirrmann grade of the PRPr group was significantly lower than that of the saline group (P< 0.01). Histological analyses showed progressive degenerative changes, including reduction of the NP area and condensation of the matrix in the saline and PRPr groups. The histological score of the PRPr group was significantly lower than that of the saline group (P< 0.01). Conclusions: PRPr has great potential to enhance the regeneration of degenerated rabbit IVDs induced by condoliase. The results of this preclinical study suggest that PRPr injection therapy may be indicated for patients with LDH who have poor recovery from disc degeneration after chemonucleolysis treatment with condoliase.

Although many studies have examined locomotive syndrome (LS) among elderly people, few studies have examined LSin young‐ and middle‐aged adults. This study aimed to provide basic data on the epidemiological characteristics of LS, including in young‐ and middle‐aged adults. We conducted a cross‐sectional survey of a nonrandom sample of 852 adults aged 18–64 (678 males, 174 females) working in five companies in Japan, between December 2015 and February 2018. LSstage was determined using the criteria proposed by the Japanese Orthopaedic Association (JOA). LSstage 0 was defined as No‐LS, and stages 1 and 2 were defined as LS. Multiple logistic regression analysis was used to investigate the independent relationship between LSand sociodemographic, smoking, alcohol drinking (AD), frequency of breakfast consumption (FBC), dietary variety score (DVS), and the University of California Los Angeles (UCLA) activity score after adjusting for age and sex. We found that 23.1% of participants were evaluated as LS, including 21.5% of males and 29.3% of females (P< 0.05). Participants aged ≥45 years exhibited higher rates of LS(males: 23.1%, females: 43.6%) compared with those aged <45 years (P< 0.05). Logistic regression analysis revealed that age, body mass index (BMI), AD,UCLAactivity score, and FBCwere also related to LS. Education initiatives about LSshould be targeted not only to elderly populations but also to young‐ and middle‐aged adults in the workplace.

Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA).Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III). TNC solution of 10 μg/mL was additionally injected twice after 3 weeks (group IV) or weekly after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks after surgery.Results Exogenous TNC was maintained in the cartilage and synovium for 1 week after administration. Histological scores in groups I and II were better than scores in group III at 4 and 6 weeks, but progressive cartilage damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections (groups IV and V) showed significantly better Mankin score than single injection (group II) at 8 weeks.Conclusion TNC administered exogenously remained in the cartilage of knee joints for 1 week, and could decelerate articular cartilage degeneration in murine models of OA. We also showed that sequential administration of TNC was more effective than a single injection. TNC could be an important molecule for prevention of articular cartilage damage.

The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the function of RANKL in the matrix metabolism of the rat IVD. Sprague-Dawley, 12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected thoracolumbar discs were monolayer-cultured. RANK/RANKL/OPG expression in rat IVDs was examined using real-time polymerase chain reaction (PCR) and immunohistochemical analysis (cultured cells and IVD tissues). To examine the effect of interleukin-1β (IL-1β) stimulation on the mRNA levels of RANK, RANKLand OPG, the cells were cultured with or without recombinant human IL-1β (rhIL-1β). To evaluate the effect of RANKL on the mRNA expression of catabolic factors (IL-1β, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were cultured with RANKL in the presence or absence of rhIL-1β. The immunohistochemical expression of this system was also evaluated using human IVD tissues with different grades of degeneration. mRNA expression levels of RANK, RANKL, and OPGwere clearly identified in AF, NP and CEP cells. Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes and/or cytoplasm of the three types of cells. The mRNA level of RANKLwas significantly upregulated by treatment with rhIL-1β of the three types of cells. Treatment with RANKL without rhIL-1β did not induce significant effects on the mRNA expression of catabolic factors by AF, NP and CEP cells. However, the expression was significantly upregulated by stimulation with RANKL in the presence of rhIL-1β. There was a general trend for more RANK/RANKL/OPG-positive cells in human IVD tissues in an advanced stage of degeneration compared to an early stage. Our study showed the possibility that the RANK/RANKL/OPG system may play a part in the process of intervertebral disc degeneration.

Purpose Radiological imaging in Dedifferentiated liposarcoma (DDLPS) often shows the coexistence of fatty and non-fatty solid components; however, it has been shown that when fatty components were not identified on magnetic resonance imaging (MRI), the diagnosis of DDLPS would not have been diagnosed if immunohistochemical (IHC) staining had not been performed. The aim of this study was to investigate the pattern of MRI and relationship between MRI and IHC findings in DDLPS.Methods We retrospectively reviewed the cases of 25 patients with DDLPS. To identify the MRI spectrum of DDLPS, tumors were classified into the following four categories based on MRI findings: I = a well-defined fatty mass and juxtaposed well-defined non-fatty mass, II = a non-fatty component within a predominantly fatty mass, III = a focal fatty component within a large non-fatty mass, and IV = a non-fatty mass with atypical MRI findings. IHC staining for CDK4, MDM2, and p16 were evaluated.Results Category IV tumor was the most common tumor in this population. Of the 22 patients who underwent IHC staining, MDM2, CDK4, and p16 were positive in 21, 20, and 19 patients, respectively. MDM2 was positive in all 11 patients with category IV tumors; CDK4 and p16 were positive in 10 and eight patients, respectively. There was no difference of survival between the patients with category I, II and III and category IV.Conclusions DDLPS without fatty components on MRI scans was mostly found. We recommend IHC staining to screen for DDLPS even if the tumors in STS cases have a non-fatty component.

Salubrinal is an agent that reduces the stress to the endoplasmic reticulum by inhibiting de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). We and others have previously shown that the elevated phosphorylation of eIF2α stimulates bone formation and attenuates bone resorption. In this study, we applied salubrinal to a mouse model of osteogenesis imperfecta (Oim), and examined whether it would improve Oim's mechanical property. We conducted in vitroexperiments using RAW264.7 pre-osteoclasts and bone marrow derived cells (BMDCs), and performed in vivoadministration of salubrinal to Oim (+/−) mice. The animal study included two control groups (wildtype and Oim placebo). The result revealed that salubrinal decreased expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and suppressed osteoclast maturation, and it stimulated mineralization of mesenchymal stem cells from BMDCs. Furthermore, daily injection of salubrinal at 2 mg/kg for 2 months made stiffness (N/mm) and elastic module (GPa) of the femur undistinguishable to those of the wildtype control. Collectively, this study supported salubrinal's beneficial role to Oim's femora. Unlike bisphosphonates, salubrinal stimulates bone formation. For juvenile OI patients who may favor strengthening bone without inactivating bone remodeling, salubrinal may present a novel therapeutic option.

The rotator cuff (RC) is frequently torn at the enthesis composed of fibrocartilage. We aimed to histopathologically evaluate lining layers and assess the distribution of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, and microRNA (miR)-140sin the synovia of patients with RC tears. We recruited 51 patients who underwent arthroscopic surgical treatment for full-thickness rotator cuff tears, including 26 patients with < 3 cm tear size (group N) and 25 patients with ≥ 3 cm tear size (group W). Biopsied synovia were analyzed using histological and immunohistological techniques for the presence ADAMTS4 and ADAMTS5. The layers of the synovial lining were morphologically classified into 3 grades according to the synovitis score and staining levels of ADAMTSs. The glenohumeral synovia from 8 patients with recurrent shoulder dislocation (group C) were used as controls. Furthermore, in situ hybridization was performed to evaluate the presence of miR-140sin patients with massive tears and recurrent shoulder dislocation. The staining levels were evaluated and analyzed based on comparison between patient groups and correlation between ADAMTS5 and miR-140s. Histological analysis revealed significant differences between groups W and C. ADAMTS5 and ADAMTS4 were strongly expressed in the synovial lining of patients in group W, and this expression was significantly higher than that in groups C and N. In addition, expression of ADAMTS5 was inversely correlated with that of miR-140-3p. This study showed that synovia from group W had a significantly higher rate of severely thickened areas with strong expression of both aggrecanases. Furthermore, the area with weak expression of miR-140-3pshowed strong ADAMTS5 expression.

Pedicle screw (PS) system using Ti-6Al-4V PSs became popular in spinal instrumentation system. However, they sometimes case loosening and back-out from bone because of their poor bone-bonding ability. In the present study, Ti-6Al-4V alloy was subjected to the acid-heat or calcium-heat treatments that are effective for inducing high capacities of apatite formation and bone bonding on pure Ti. When the alloy was subjected to the acid-heat treatment, a surface layer composed of rutile and anatase TiO2 enriched with Al and V was produced. Thus the treated alloy was neutrally charged and did not form apatite in a simulated body fluid (SBF) even after 3 day. In contrast, when the alloy was subjected to the Ca-heat treatment, a surface layer composed of calcium titanate, anatase and rutile free from Al and V was produced. The treated alloy formed apatite in SBF within 3 days. When the Ti-6Al-4V PSs subjected to the Ca-heat treatment was implanted into vertebra of beagle dogs, they showed higher bone-bonding ability as well as bone contact area than those without the treatment. This kind of bioactive Ti-6Al-4V PSs might be useful for spinal instrumentation since they could prevent loosening and back-out from bone.

Background Patient satisfaction and expectations are now recognized as an outcome measure for successful total knee arthroplasty (TKA). The purpose of this study was to determine which factors including soft tissue balance during surgery affect patient satisfaction and expectations after TKA.Methods A total of 135 patients (157 knees) with knee osteoarthritis who underwent primary TKA with a posterior stabilized design were studied. After implantation of all components, varus/valgus laxity of the knee was measured intraoperatively with the knee at 0°, 30°, 60°, 90°, and 120° guided by an image-free navigation system. Factors that affected patient satisfaction and expectations, including lateral and medial laxities, were evaluated using the 2011 Knee Society score.Results The mean intraoperative lateral laxity was 1.1°, 1.6°, 0.9°, 1.3°, and 1.7° with the knee at 0°, 30°, 60°, 90°, and 120°, respectively. The mean intraoperative medial laxity was 1.1°, 1.4°, 1.1°, 1.1°, and 1.7° with the knee at 0°, 30°, 60°, 90°, and 120°, respectively. Patient satisfaction after TKA correlated positively with symptom (R = 0.61, p< 0.01) and functional activity (R = 0.47, p< 0.01) scores. Patient expectations after TKA weakly positively correlated with symptom (R = 0.29, p< 0.01) and functional activity (R = 0.20, p= 0.01) scores, and weakly negatively with medial laxity at 30° (R = −0.21, p< 0.01).Conclusion Midflexion medial laxity was associated with worse patient expectations after TKA. Avoiding medial laxity could be one of the important techniques during TKA.

The purpose of this study was to determine the prevalence of adverse reactions to metal debris (ARMD) following large-diameter metal-on-metal total hip arthroplasty. The authors examined the potential for using magnetic resonance imaging to screen for pseudotumors in 108 hips 2 years postoperatively. Serum cobalt and chromium concentrations were measured in 80 hips that underwent unilateral total hip arthroplasty. The authors considered pseudotumors and aseptic lymphocyte-dominated vasculitis-associated lesions to be ARMD and compared metal ion levels between hips with ARMD (ARMD group) with hips with no ARMD (non-ARMD group).Magnetic resonance imaging revealed pseudotumors in 9 patients (10 hips, 9%). Five of these 10 hips were symptomatic and underwent revision surgery. Two other patients underwent revision surgery due to symptomatic cup loosening with aseptic lymphocyte-dominated vasculitis-associated lesions. Ten patients (12 hips) had ARMD. Serum cobalt and chromium concentrations were significantly higher in hips with ARMD than hips without ARMD. Other factors, including age, body mass index, sex, clinical score, acetabular cup inclination angle, and femoral head diameter, were not significantly different between the groups.Elevated metal ion levels suggest that ARMD is associated with increased metal wear. Magnetic resonance imaging provides sensitive screening for pseudotumors following metal-on-metal total hip arthroplasty.

Clinical case-control and cross-sectional study.

We report a case of recurrent knee valgus deformity in a patient with Ellis–van Creveld syndrome. Varus osteotomy, distraction osteogenesis, or epiphyseal stapling is one treatment option for valgus malalignment to improve appearance, gait, and function. However, surgical correction of valgus knee deformity by varus osteotomies of the proximal tibia was not maintained postoperatively, necessitating additional varus osteotomies of the distal femur in this case. The main cause of recurrence was attributed to large bony defect of the anterior segment of the proximal tibia, in addition to depression of the lateral tibial plateau.

During the past 20 years, we have found that acridine orange (AO) selectively accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal effects against sarcoma cells in vitro after illumination of the tumor cells with visible light or irradiation of the cells with low-dose X-rays. Based on the data obtained from basic research, we have employed reduction surgery followed by photo- or radiodynamic therapy using AO (AO-PDT & RDT) in 71 patients with musculoskeletal sarcomas, in an attempt to maintain excellent limb function in the patients. We have obtained good local control rates and remarkably better limb functions with this approach as compared to the results obtained with the conventional wide resection surgery. Our basic research demonstrated that AO accumulates densely in intracellular acidic vesicles, especially lysosomes, in an acidity-dependent manner. In cancer cells that proliferate under hypoxic conditions or with Warburgs effect, active glycolysis produces an enormous number of protons, which are released by the cells via proton pumps into the extracellular fluid or lysosomes to maintain a neutral pH of the cytosolic fluid. Cancer cells contain many strongly acidic lysosomes of large sizes; therefore, AO shows marked and prolonged accumulation in the acidic lysosomes of cancer cells. Photon energy excites the AO resulting in the production of activated oxygen species, which oxidize the fatty acids of the lysosomal membrane, resulting in the leakage of lysosomal enzymes and protons, followed by apoptosis of the cancer cells. Based on these observations, we conclude that AO-PDT & RDT target acidic vesicles, especially the lysosomes, in cancer cells, to exhibit selective anti-cancer cell activity. Therefore, it is suggested that AO excited by photon energy has excellent potential as an anticancer “Magic Bullet”.

OBJECTIVE: Although osteoarthritis (OA) is generally assessed using standard radiographic images in clinical practice, biochemical markers can be used to detect the disease and determine its severity. Osteopontin (OPN) is an extracellular matrix glycoprotein that is a potential inflammatory cytokine. Presence of the thrombin-cleaved form of OPN is well correlated with various inflammatory diseases. We examined whether thrombin-cleaved OPN in synovial fluid (SF) and synovium could be associated with the severity of knee OA. METHODS: SF samples were obtained from 139 knees with OA. Thrombin-cleaved OPN product was determined using Western blotting. Levels of thrombin-cleaved and full-length OPN in SF were determined by ELISA. Synovium samples were analyzed by immunohistochemistry using an antibody specific to the thrombin-cleaved form. RESULTS: Western blotting showed the presence of thrombin-cleaved OPN in SF from patients with advanced OA. Concentrations of OPN full-length in OA knees were not statistically different from those in controls (p = 0.134). In contrast, levels of OPN N-half were significantly higher in OA knees than in controls (p = 0.042). Statistically significant correlation was found between thrombin-cleaved OPN and disease severity by Kellgren-Lawrence grade 1, 2, 3, and 4 (R = 0.274, p < 0.001). Immunohistochemistry of the synovium showed stronger reactivity in samples from subjects with advanced OA. CONCLUSION: Local generation of thrombin-cleaved OPN was increased with greater OA severity.

Purpose. To compare percutaneous transpedicular vertebroplasty using calcium phosphate cement (CPC) versus conservative treatment for osteoporotic vertebral fractures.Methods. Eight men and 28 women aged 61 to 99 (mean, 80) years with osteoporotic vertebral fractures underwent percutaneous transpedicular vertebroplasty using CPC. During the same period, 6 men and 32 women aged 53 to 93 (mean, 77) years underwent conservative treatment. The indication for vertebroplasty was a painful unstable fracture, with mobility of the vertebral body shown on flexion and extension lateral radiographs. Fractures without mobility despite deformity were treated conservatively.Results. In the vertebroplasty group, all patients benefited from reduced back pain immediately after surgery, and pain relief was maintained at the latest follow-up. However, correction loss continued until one month after the operation. The mean visual analogue score for pain decreased significantly from preoperation to one day after surgery (9.3 vs. 6.2, p=0.02), and further decreased to 2.8 (p=0.04) on day 3 or 4 when ambulation began, and to 1.5 at the one-month follow-up and 1.4 at the final follow-up (mean, 14 months). The mean duration of analgesic treatment was significantly shorter in the vertebroplasty than conservatively treated group (10.2 vs. 63.5 days). All patients in the vertebroplasty group achieved bone union, with no adjacent vertebral fractures. However, in patients having conservative treatment, there were 2 adjacent vertebral fractures and 4 pseudarthroses, and the collapse continued for several months.Conclusion. Percutaneous transpedicular vertebroplasty using CPC achieves immediate pain relief and reduces the risk of vertebral body collapse and pseudarthrosis among elderly patients with osteoporotic vertebral compression fractures.

Purpose. To assess the association between vertebral fractures and mortality.Methods. 419 women and 210 men aged 60 to 98 (mean, 73) years participated in an osteoporosis screening exercise. Patient age, gender, comorbidity, lumbar pain, smoking, and alcohol consumption were recorded, as were the number of vertebral fractures and bone mineral density. Vertebral fractures were evaluated using lateral radiographs and quantitative morphometry. Anterior, central, and posterior vertebral heights were measured; vertebral fractures were defined as a decrease of =20% in any of these heights.Results. 131 (21%) of the participants had vertebral fractures. At the 10-year follow-up, 121 (19%) of the participants (55 men and 66 women) had died; 43 of them had vertebral fractures and 78 did not. The respective 10-year survival rates for participants with and without vertebral fractures were 69% and 86% (p<0.0001). The survival rate was lower in those with greater number of vertebral fractures (76% for those with one or 2 fractures and 50% for those with =3 fractures). Multiple regression analysis showed that advanced age (p<0.0001), male gender (p=0.003), and presence of vertebral fractures (p=0.013) correlated significantly with survival.Conclusion. The presence and number of vertebral fractures were associated with mortality. Prevention of vertebral fractures may be important for improving the prognosis of patients with osteoporosis.

Tophaceous pseudogout in the knee joint is rare. We report an 82-year-old man who presented with a one-year history of pain and swelling of the right knee joint. Treatment with non-steroidal anti-inflammatory drugs and aspiration of the joint effusion had not been effective. The mass continued to enlarge, and the patient had difficulty walking. Radiographs and computed tomography showed meniscal calcification with an abnormal soft-tissue mass surrounded by calcification. After excision, massive calcified deposits were seen both inside and on the surface of the tophaceous pseudogout. The deposits showed birefringence under polarised light, suggestive of calcium pyrophosphate dihydrate crystals. At the 2-year follow-up, the patient could walk independently without knee pain or swelling, although his range of knee motion was slightly limited due to joint contracture that developed before surgery.