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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.

Byline: Tomoki. Nakamura, Akihiko. Matsumine, Koichiro. Yamakado, Motoshi. Takao, Atsumasa. Uchida, Akihiro. Sudo Background: The incidence of sarcoma diagnosed in the elderly population may be rising due to the increasing [...]

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.

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 μg 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.

OBJECTIVE: Osteopontin (OPN) is an extracellular matrix glycoprotein that has been recognized as a potential inflammatory cytokine. The function of OPN is modulated by protease digestion, and a thrombin-cleaved form of OPN is involved in the pathogenesis of various inflammatory disorders. We examined thrombin-cleaved OPN products in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial fluid samples were obtained from knees of 20 patients with RA and 111 patients with OA. Thrombin-cleaved OPN product was determined using Western blotting. Levels of thrombin- cleaved and full-length OPN in synovial fluid were determined by ELISA. Synovia were analyzed by immunohistochemistry using an antibody specific to the thrombin-cleaved form. RESULTS: Immunoblotting showed the presence of thrombin-cleaved OPN in synovial fluid from patients with RA and OA. ELISA results showed no difference between concentrations of full-length OPN in the synovial fluid of RA and OA patients; however, thrombin-cleaved OPN concentrations in RA synovial fluid samples were roughly 30-fold higher compared with OA samples (p < 0.001). Synovial fluid concentrations of thrombin-cleaved OPN in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA than in OA samples. CONCLUSION: Local generation of thrombin-cleaved OPN was increased in RA joints. Thrombin-cleaved OPN may be a useful biochemical marker of RA.

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.

Background: Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. The intra-articular injection of monosodium iodoacetate (MIA), which is commonly used in animal models of osteoarthritis, induces cartilage degeneration and progressive arthritis in a dose- and time-dependent manner. The purpose of this study was to determine the effect of MIA injections into rabbit IVDs on the progression of IVD degeneration evaluated by radiographic, micro-computerized tomography (micro-CT), magnetic resonance imaging (MRI), and histological analyses. Methods: In total, 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1–L2 to L4–L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1–L2: CA only; L2–L3: MIA 0.01 mg; L3–L4: 0.1 mg; L4–L5: 1.0 mg; L5–L6: non-injection (NI) control). Disc height was radiographically monitored biweekly until 12 weeks after injection. Six rabbits were sacrificed at 2, 4, 8, and 12 weeks post-injection and processed for micro-CT, MRI (T2-mapping), and histological analyses. Three-dimensional (3D) disc height in five anatomical zones was evaluated by 3D reconstruction of micro-CT data. Results: Disc height of MIA-injected discs (L2–L3 to L4–L5) gradually decreased time-dependently (P&lt; 0.0001). The disc height of MIA 0.01 mg-injected discs was significantly higher than those of MIA 0.1 and 1.0 mg-injected discs (P&lt; 0.01, respectively). 3D micro-CT analysis showed the dose- and time-dependent decrease of 3D disc height of MIA-injected discs predominantly in the posterior annulus fibrosus (AF) zone. MRI T2 values of MIA 0.1 and 1.0 mg-injected discs were significantly decreased compared to those of CA and/or NI controls (P&lt; 0.05). Histological analyses showed progressive time- and dose-degenerative changes in the discs injected with MIA (P&lt; 0.01). MIA induced cell death in the rabbit nucleus pulposus with a high percentage, while the percentage of cell clones was low. Conclusions: The results of this study showed, for the first time, that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs in a time- and dose-dependent manner. This study suggests that MIA injection into rabbit IVDs could be used as an animal model of IVD degeneration for developing future treatments.

Background: Soluble fibrin (SF) is considered to be useful for the diagnosis of thrombosis, however, evidence for the diagnosis of pre-thrombosis by SF is still not well established. Objective: The present study was designed to evaluate the usefulness of new SF assay (New SF) in the diagnosis of thrombosis and a pre-thrombotic state. Patients/Methods: The plasma concentrations of New SF were measured in 748 inpatients suspected to have thrombosis and they correlated with thrombosis. Results and Conclusions: The plasma concentrations of New SF were significantly higher in patients with disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and cerebral thrombosis, in comparison to those of patients without thrombosis, but there was no significant difference of the New SF assay between patients with thrombosis and those after an operation. The New SF assay was moderately correlated with the other two SF assays. The New SF levels were significantly higher in patients before the onset of thrombosis than in those without thrombosis but other hemostatic molecular markers were not significantly elevated. Our findings suggest that the New SF assay is useful for the diagnosis of not only thrombosis but also of a pre-thrombotic state.

Expression of tenascin-C reappears in articular cartilage of persons with osteoarthritis (OA), while it is almost abolished in normal mature cartilage. Tumor necrosis factor- (TNF-), a proinflammatory cytokine, is upregulated in OA cartilage and is involved in the progression of OA, and stimulates tenascin-C expression in other types of cells. We investigated regulation of tenascin-C expression by TNF- through nuclear factor-B (NF-κB) in OA cartilage in vivo and in vitro. METHODS: Human articular cartilages were obtained from patients with OA and immunofluorescence examination of tenascin-C and the activated RelA subunit was performed. Cultured chondrocytes isolated from human OA cartilage were treated with TNF- and with SN50. Activation of RelA subunit of NF-κB was examined by immunolabeling. Changes in tenascin-C protein concentrations were determined by immunofluorescence of cells after monensin treatment and Western blot analysis of the cell lysates, and mRNA levels were analyzed by quantitative real-time polymerase chain reaction. RESULTS: Increased intensity of tenascin-C staining was observed in the damaged cartilage compared with normal cartilage. Activated RelA staining in chondrocyte nuclei was prominent in tenascin-C-positive areas of OA cartilage. Treatment of cultured chondrocytes by TNF- induced translocation of activated RelA to the nuclei, followed by upregulation of tenascin-C expression in both mRNA and protein. Treatment with SN50 inhibited increases of RelA and tenascin-C expression in chondrocytes. CONCLUSION: TNF- stimulated tenascin-C expression through NF-κB signaling with RelA activation in cultured OA chondrocytes, suggesting involvement of tenascin-C in OA cartilage remodeling.

In the past, patients admitted for hip fractures had often sustained a contralateral hip fracture. The incidence of bilateral hip fractures has been reported to be 5%–10%, and in the future the number of bilateral hip fractures is expected to increase with the increase of unilateral hip fractures. We believe that bilateral hip fractures can be efficiently prevented if a fracture on the other side could be predicted after unilateral hip fracture. Therefore, this retrospective study of 835 patients with hip fractures investigated the incidence, prognosis, and risk factors of bilateral hip fractures.

In ceramic-on-ceramic total hip arthroplasty (THA), modular acetabular component with a sandwich insertion was developed and evaluated mid-term clinical results. 35 hips had undergone cementless ceramic-on-ceramic THA with sandwich cup (Kyocera, Kyoto, Japan). The mean duration of follow-up was 5 years. 6 hips had undergone component revisions. The reasons for revision included infection in 1 hip, dislocation with loosening in 2 hips, alumina liner fractures in 2 hips, and cup dissociation in 1 hip. All femoral and acetabular components showed no loosening in the unrevised hips at the time of the last follow-up. None of the 29 unrevised hips had osteolysis.

A novel hydroxyapatite (HA-A) was developed and we evaluated the slow release of antibiotic in vitro as well as osteoconduction of the material in vivo. HA-A (4 x 4 mm) was synthesized by mixing HA powder, gelatin, and vegetable oil. The material had a bi-modal pore size distribution, with intragranular (10 nm to 10 µm) and intergranular (100 µm) pores, and porosity of 40 vol%, while a control HA had pore sizes ranging from 50 to 300 µm and identical porosity. In vitro drug release was tested using antibiotics soaked on the HA cylinders using a vacuum system. The mean adsorption efficiency was higher for HA-A than for control and higher levels of antibiotic were released from HA-A. Bone ingrowth into the pores was observed for both materials. Since the novel HA showed both the slower release of antibiotic (nanosize pores) and supported excellent osteoconduction (microsize pores), it could be useful for the treatment of osteomyelitis.

OBJECTIVE: Osteoarthritis (OA) is a major cause of disability and represents the most common disease in the aging population. Although the course of the disease is generally assessed using standard radiographic images, biochemical markers may be employed to detect the disease and determine the degree of severity. We developed an enzyme linked immunosorbent assay (ELISA) system using a monoclonal antibody specific for the large-splice variants of tenascin-C (TN-C) and examined whether TN-C in synovial fluid (SF) is an adequate biochemical marker of OA progression. METHODS: SF samples were obtained from knees of 74 patients with OA and 16 without OA. Based on the radiographic grading of the OA severity, the knees were divided into 3 groups: mild, moderate, and severe OA. Expression of TN-C splice variants was examined using immunoblotting. TN-C concentrations were determined by ELISA. RESULTS: Western blotting showed the presence of large TN-C variants in SF from severe OA. TN-C levels were 5-fold higher in OA samples compared to subjects without OA (p < 0.0001). TN-C levels were not different between control cases and mild OA, but increased significantly in moderate (p = 0.0244) and severe OA (p < 0.0001). After adjusting TN-C levels for age, body mass index, and sex, TN-C levels correlated with radiographic progression of knee OA (R2 = 0.404, p < 0.0001). CONCLUSION: TN-C, including the large-variant subunits, is a useful biochemical marker for OA progression in the later stages of disease.

Our study focuses on the antineoplasmic action of hyperthermia. In this study, use of a heat-generating cement was exploited for the management of pathological and impending fractures in malignancies. The cement contains magnetic powder in ceramic particles and generates wellregulated heat when a magnetic field is applied externally. Eighteen rabbits were inoculated with blocks of VX2tumor into one of their tibia. One week after the procedure, 9 rabbits were exposed to a magnetic field (HT group) while the remaining 9 rabbits were not (non-HT group). In rabbits killed between 20 and 42 days after the VX2inoculation, the circumference of the operated leg was 7.9 ± 0.3cm and 10.2 ± 1.0cm (mean ± SE) in HT and non-HT groups, respectively (P< 0.05). Histological findings revealed the regressive change in tumor tissue of the HT group. By radiographs, pathological fractures and cortical bone destruction were seen in 5 and 8 rabbits in the non-HT group, respectively, but in the HT group these effects were absent in all the rabbits except 1 in which a definite diagnosis has not been made. Our findings demonstrate that controlled hyperthermia therapy using a newly developed bone cement suppresses tumor growth and prevents local bone destruction caused by VX2tumors.

Freshly isolated human blood monocytes expressed neither c-src mRNA nor c-Src. However, when monocytes were incubated with anti-CD98 heavy chain (HC) mAb, expression of c-src mRNA, c-Src, and activated c-Src was induced. Many binding sites for the ubiquitous transcription factor Sp1 were identified in the promoter region of the c-src gene. Surprisingly, Sp1 and Sp1 mRNA were not found in monocytes that were freshly isolated or incubated with control antibody. Stimulation with anti-CD98HC mAb also resulted in the expression of Sp1 and its translocation to the nucleus. Herbimycin A, genistein, manumycin A, PD-98059, SB203580, and HBJ127 suppressed CD98HC-mediated c-src and Sp1 mRNA induction. On the contrary, H-7, Wortmannin, HA1077, and Y-27632 showed no effect on c-Src and Sp1 induction. Furthermore, anti-CD98HC mAb induced activation of tyrosine kinases and ERK kinases. These findings suggest that the tyrosine kinase(s)-Ras-MAPK-Sp1 pathway(s) is involved in CD98HC-mediated induction of c-Src in human blood monocytes.

Spindle‐shaped cells were established from four giant‐cell tumors of bone. When human blood monocytes were co‐cultured with these cells, multinucleated giant‐cell formation of monocytes was induced. Intriguingly, even when a filter (pore size: 0.45 μm) was interposed between monocytes and the spindleshaped cells, polykaryocytes also appeared. These multinucleated giant cells were positive for tartrateresistant acid phosphatase, expressed calcitonin receptor, and showed bone‐resorption activity, characteristics of osteoclast‐like cells. These findings indicate that soluble factors secreted from these cells play an important role in osteoclast‐like cell formation from blood monocytes. These data additionally suggest that these cells support osteoclast‐like cell formation in giant‐cell tumors of bone. The cells also expressed mannose receptor, fibronectin, receptor activator of nuclear factorkB, and several cytokine mRNAs, including interleukin‐6, receptor activator of nuclear factorkB ligand/osteoclast differentiation factor/osteoprotegerin ligand, and macrophage colony‐stimulating factor, However, all of these molecules except receptor activator of nuclear factorkB ligand mRNA could also be detected in control HeLa and CV‐1 cells. Although the soluble receptor activator of nuclear factorkB ligand has not been found under physiological conditions, it is possible that it is cleaved by cellular proteases and the truncated receptor activator of nuclear factorkB is released from cells. Identification of the soluble factors capable of inducing osteoclast formation from blood monocytes is a pressing problem to be solved.

We investigated the difference in osteoclast formation between patients with osteoporosis and two healthy control groups by inducing it from peripheral blood monocytes with use of anti‐fusion regulatory protein‐1 monoclonal antibody. The group of patients with osteoporosis consisted of 35 women and excluded secondary osteoporosis, and the control groups consisted of 12 young healthy volunteers (control I) or 10 individuals age‐matched to the patients with osteoporosis (control II). Osteoclast formation declined with age between the two control groups, but this decline was not significant. Fusion rate and the mean number of nuclei in osteoclasts were significantly less in the patients with osteoporosis than in the young or agematched controls. It was clearly demonstrated that the ability of monocytes to fuse declines significantly in patients with osteoporosis.

Abstract: We evaluated 207 individuals (49 men and 158 women) living in a small town in central Japan to identify the risk factors for, and the etiology of, osteoporosis. Female sex, advanced age, short stature, low body weight, and deficiencies in calcium and protein intake were associated with an increased risk of osteoporosis. Nutrition appeared to be strongly related to a decrease in bone mass, because subjects who lived solitary lives were more likely to have decreased bone mass and bone mass was similar between husbands and wives.

We have developed a new and simple system of human osteoclast formation by fusing peripheral blood monocytes with anti‐Fusion Regulatory Protein‐1 (anti–FRP‐1) monoclonal antibody (mAb). When human blood monocytes were cultured in the presence of anti‐FRP–1/CD98 mAbs, polykaryocytes began to appear at approximately 15 h and increased in size with time until 3–4 days of incubation with anti–FRP‐1 mAb. These fused cells showed positive staining in tartrate‐resistant acid phosphatase, possessed numerous calcitonin receptors, and were capable of bone resorption. These results strongly suggest that anti–FRP‐1 antibody‐induced multinucleated cells are osteoclasts. Furthermore, FRP‐1 antigens were detected in osteoclasts isolated from human bone and in the osteoclast‐like cells obtained from human giant cell tumors of bone.

Pseudoexstrophy is a rare, mild exstrophy variant characterized by the major musculoskeletal defects of the exstrophy complex without associated defects of the urinary system. The authors present a case of pseudoexstrophy with a small omphalocele and wide pubic diastasis (greater than 4 cm). Only three cases of pseudoexstrophy with omphalocele have previously been described worldwide, and this is the first reported case with wide pubic diastasis. Successful two-stage surgery consisting of omphalocele repair in the neonatal period and abdominoplasty with iliac osteotomy after the age of 6 months is described.

Locomotion training (LT) consisting of single‐leg standing and squatting was developed to help prevent locomotive syndrome (LS), and is typically used in older people. The objective of this study was to examine the effects of LT on young and middle‐aged people. This study was performed at two companies. Workers in company A engaged in LT five times/week for 1 year, whereas workers in company B did not. Baseline and follow‐up checkups consisted of questionnaires and physical performance tests, including three kinds of locomotion tests. In total, 88 and 101 workers in companies A and B, respectively, met the inclusion criteria. LS stage, stand‐up test results, and scores on a geriatric locomotive function scale significantly improved among workers in company A, but only stand‐up test results significantly improved among workers in company B. Quadriceps power increased in company A, but did not change in company B. Especially, workers with LS in company A had more significant changes than those without LS and those in company B. The results of this longitudinal study suggest that LT is useful even for young and middle‐aged workers. LT was especially more effective for workers than those without LS.

Introduction. In cases of bone deficiency or osteoporosis, and especially in revision cases, there were only two options for treatment until the impaction bone graft procedure was proposed. These were cemented or cementless femoral prosthesis. In the early 1990s, the use of impaction bone graft with a cemented mantle had gained popularity and had proven to be clinically effective. In Germany, a cementless impaction bone graft procedure using Corail® (DePuy Synthes) stems was devised, and functional scores were similar to conventional cemented Impaction bone grafts. Case presentation. A 48-year-old man presented with femur loosening of a reamed bipolar arthroplasty performed in 1990. The patient was treated with a cementless impaction bone graft using a Corail® (DePuy Synthes) stem in the femur in revision THA surgery, and the calcar was reconstructed by allograft. Results. At five years, the calcar allograft united with the host bone, and the femoral component showed no subsidence. Conclusion. Calcar reconstruction with a strut allograft, aimed at preventing sinking of the stem was key in this operation. Surgical indication for femoral cementless impaction bone graft should be for loosened femoral prosthesis in a type II Paprosky classification, where only the cortical bone of the isthmus is partially affected, cortical thinning does not exist, and it is mechanically strong enough for the allograft tip impaction. The procedure was safely feasible through the direct anterior approach.

With improving prognosis for recipients of liver transplantation, the necessity of medical care for musculoskeletal disorders, including spinal diseases, of these patients is also increasing. Only a few reports are available on cases of spine surgery following liver transplantation. Furthermore, a case of lateral access surgery following liver transplantation has not thus far been reported. The purpose of this study is to present the first two cases of patients treated with lateral access spine surgery following liver transplantation. Case 1. A 49-year-old female had received living donor liver transplantation (LT) for acute-on-chronic liver failure (ACLF) ten years prior to spine surgery. The patient underwent two levels of lateral lumbar interbody fusion (LLIF) followed by posterior lumbar interbody fusion (PLIF) for degenerative lumbar disease. Although neurological symptoms in the lower extremity improved, a liver disorder resulting from acetaminophen-induced hepatotoxicity occurred at an early stage following spine surgery. Case 2. A 66-year-old female had received living donor liver transplantation for hepatocellular carcinoma (HCC) six years prior to spine surgery. She underwent posterior instrumentation surgery followed by a T12 corpectomy using a wide-foot print expandable cage for T12 vertebral collapse. Following surgery, her weakened muscle strength in the lower extremities was significantly improved. Lateral access spine surgery for lumbar and thoracolumbar lesions can be successfully performed for patients following liver transplantation. However, careful follow-up should be performed for complications related to the function of the liver graft following spine surgery.

Femoral shaft nonunion after the intramedullary nailing has been successfully treated with advances in surgical technique. Nonetheless, the techniques cause morbidity to periosteum at the fracture site. We report the case of a 67-year-old man who underwent endoscopic surgery for refractory nonunion following the fracture of the distal femoral shaft, despite two fixations using an interlocking nail. In addition, the patient had uncontrolled diabetic mellitus. Endoscopy allowed us to acquire a clear view of the nonunion site, in which the resection of scar tissues and the packing of the cancellous bone were performed. At the final follow-up, bone healing was observed, and the patient was able to return to normal daily and social activity.

We report a case of late small intestine perforation by an acetabular cup fixation screw after total hip arthroplasty (THA). A 79-year-old-woman underwent THA for hip osteoarthritis 13 years previously at another hospital. Although the acetabular cup fixation screw protruded into the pelvis, she had no symptoms. She later presented with peritonitis and was admitted to the hospital and prescribed antibiotic therapy. Computed tomography showed that the screw was adjacent to the intestine and was the likely cause of her peritonitis. After the peritonitis healed, she was referred to our hospital for surgical treatment of the screw. During laparotomy, we performed a resection of the intra-pelvic portion of the screw. The screw perforated the small intestine, so a small intestinal resection was also performed. The patient had an uneventful recovery.

Ochronotic arthropathy is a manifestation of long-standing alkaptonuria, a rare hereditary metabolic disorder characterized by the absence of the enzyme homogentisic acid oxidase. We describe a patient who developed rapidly progressive destructive ochronotic arthropathy in his knee and hip joints and underwent successful bilateral total knee and hip arthroplasties.