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Objective We have previously reported that stimulation of mouse bone marrow-derived macrophages with tumor necrosis factor (TNF) and interleukin-6 (IL-6) induces differentiation of osteoclast-like cells. We undertook this study to clarify the characterization and function of human TNF and IL-6-induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. Methods Peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL-6-induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was examined. Results Peripheral blood monocytes stimulated with a TNF and IL-6-induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL-6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL-6-induced osteoclast formation. Expression levels of IL1β, TNF, IL12p40, and MMP3 were significantly increased in TNF and IL-6-induced osteoclasts, but not in RANKL-induced osteoclasts. The number of TNF and IL-6-induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL-induced osteoclast numbers negatively correlated with the whole-body BMD of the same patients. Conclusion Our results demonstrate that TNF and IL-6-induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.

To validate and establish targets for the physician-based clinical scale for foot surgery in rheumatoid arthritis (RA) patients based on patient-reported outcomes from a multicenter prospective cohort.We collected data on demographics, values from the RA foot and ankle scale by the Japanese Society for Surgery of the Foot (JSSF-RA), and patient-reported outcomes (PROs) including the Health Assessment Questionnaire Disability Index (HAQ-DI) before (baseline) and 6 and 12 months after joint surgery. Target values for JSSF-RA were determined according to the lower limit of the 95% CI of JSSF-RA in patients with HAQ-DI ≤0.5 after adjusting for age and sex. We used multiple linear regression analysis to examine potential predictors of JSSF-RA target achievement at baseline.Cross-sectional analysis was conducted on data from 417 cases. The JSSF-RA target for foot and ankle surgery was set at 74 according to the JSSF-RA value corresponding to HAQ-DI ≤0.5 (mean 77.6, 95% CI: 74.3-80.9). Longitudinal analysis of patients who underwent foot surgery (A JSSF-RA value of 74 represents an important target for patients with RA who have undergone foot surgery. In order to achieve this target, the timing of the surgery should be considered in the treatment of established RA patients.

X-ray Talbot-Lau interferometry is one of the x-ray phase imaging methods that has high sensitivity in depicting soft tissues. Unlike earlier x-ray phase imaging methods that required particular types of x-ray sources, such as a synchrotron or a micro-focus x-ray tube, x-ray Talbot-Lau interferometry enables to perform clinical x-ray phase imaging using a conventional x-ray source with a relatively compact configuration. We developed an apparatus to depict cartilage in the metacarpophalangeal joints of the hands. In addition, we examined the apparatus performance by applying it to healthy volunteers and patients with rheumatoid arthritis (RA). Cartilage deformation, which is thought to be a precursor of destruction of the joints, was successfully depicted by the apparatus, suggesting a potential early diagnosis of RA.

Background It is unclear whether antecedent primary malignancies (APMs) have any negative impact on the prognosis of soft tissue sarcoma (STS). We retrospectively reviewed STS patients with APMs (STS-APM) and compared their survival to those of STS only (STS-O). Methods Twenty-one cases of STS-APM from 2008 to 2017 in our institution were analyzed. One hundred and seventy cases of STS-O at the same period were compared as a control group. Overall survival was estimated using Kaplan-Meier survival curves and prognostic factors were analyzed using logistic regression analyses and contingency table analyses. Results As the final status of STS-APM patients, 12 patients were in disease-free survival, 5 were alive with disease, 3 have died of disease, and 1 has died of another disease. There was no case that died of APM. The 5-year overall survival rates were 88% in STS-APM and 78% in STS-O, showing no statistical significant ( p = 0.65). The 5-year overall survival rates in each stage of STS-APM and STS-O were 100/100% in stage I, 100/85% in stage II, 86/72% in stage III, and the 3-year overall survival rates were 67/51% in stage IV, with no statistical significance. With regard to prognostic factor, histological grade of STS was the only significant factor. Although antecedent radiotherapy tended to show a high odds ratio, the association was not statistically significant. Antecedent chemotherapy did not show any estimated prognostic risk. Conclusions Our study suggested that APM in STS patient would not be a negative prognostic factor.

Objective This prospective observational cohort study aimed to set targets for lower limb joint surgery based on the Timed Up and Go test (TUG), an objective functional outcome measure, in patients with established rheumatoid arthritis (RA). Methods We validated TUG as an outcome measure of lower limb joint surgery and compared it with changes in patient-reported outcomes, including the Health Assessment Questionnaire Disability Index (HAQ-DI) and European Quality of life scale with five dimensions (EQ-5D). Changes in these outcomes were compared by performed surgery and by achievement of the minimal clinically important difference (MCID) for EQ-5D using univariate analysis of variance. Associations between TUG and HAQ remission (HAQ-DI ≤0.5) were determined using logistic regression analysis. Cut-off values of TUG at baseline and 6 months after surgery for HAQ remission were determined using receiver operating characteristic curves. Results A total of 126 patients were analyzed. Mean age, HAQ-DI, and TUG were 65.4 years, 1.036, and 12.8 seconds, respectively. After surgery, patients showed improvements in TUG as well as HAQ-DI. TUG at 6 months after surgery was significantly associated with HAQ remission (adjusted OR: 0.78; 95% CI: 0.65-0.93). TUG cut-off values at baseline and 6 months after surgery for achieving HAQ remission were 12.1 and 8.8 seconds, respectively. Significant improvements in TUG (∆TUG, 3.7 seconds) were associated with achievement of the MCID for EQ-5D (≥0.05) at 6 months after surgery. Conclusion Timed Up and Go test is a useful tool for assessing the outcome of lower limb joint surgery in RA patients. We propose that TUG ≤9 seconds could be an objective target for achieving good physical function after lower limb joint surgery.

Type 3 internal hemipelvectomy involves resection of the pubis. We report on 2 patients who underwent type 3 internal hemipelvectomy. One patient developed a bladder hernia, tumour recurrence, and a pathological fracture of the proximal femur. These were resolved with external hemipelvectomy 7 months later. Another patient underwent additional fascia lata transplantation to prevent development of hernia. Both patients had a stress fracture in the contralateral posterior ilium mimicking bone metastasis.

Daily and weekly administration of teriparatide (PTH1–34) reduces the risk of osteoporotic bone fractures. However, their effects on markers of bone formation and bone resorption differ. These results indicate that the dosing frequency of teriparatide may affect bone metabolism and bone structure, with different effects on bone strength. In the present study, to evaluate the dose-related effects of a low administration frequency of teriparatide on bone status, we investigated the effects of three-times-weekly administration of teriparatide (1.1, 5.6, or 28.2 µg/kg) for 12 months on bone parameters, including bone metabolism markers, bone mineral density (BMD), micro-computed tomography, and bone strength, using 6-month-old ovariectomized (OVX) rats. Three-times-weekly administration of teriparatide dose-dependently increased the BMD of the lumbar vertebra and femur in OVX rats, and increased serum osteocalcin (a marker of bone formation), but not type I collagen C-telopeptide (a marker of bone resorption). The trabecular number and thickness increased in the vertebrae and femur, as in prior reports of daily teriparatide administration in OVX rats. Cortical thickness increased only toward the endocortical side of the femur, unlike with daily administration. Bone strength of the vertebrae and proximal and shaft of the femur was correlated with the changes in BMD and bone structure. These results demonstrate the effects of low frequency, intermittent administration of teriparatide on the biomechanical, and microstructural properties of bone in OVX rats. Electronic supplementary material The online version of this article (doi:10.1007/s00223-015-9998-0) contains supplementary material, which is available to authorized users.

Aim This study aimed to validate the Timed Up and Go test (TUG) for measuring objective functional impairment in patients with established rheumatoid arthritis (RA) based on a prospective observational cohort of RA patients undergoing joint surgery. Methods We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI and other patient-reported outcomes, including European Quality of life scale (EQ-5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI ≤0.5), normal HAQ (HAQ-DI ≤0.25), and the absence of disability in each HAQ-DI category were also determined by age. Results A total of 435 patients were enrolled and analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ-DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising, walking, reach and activity). After adjusting for age and sex, mean TUG values were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4-10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were 7.2 sec (5.9-8.5) in young patients (≤61 years), 9.1 sec (7.6-10.5) in middle-aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (≥71 years). Conclusion TUG was significantly associated with functional impairment and aging in patients with long-standing RA. Thus, TUG could be useful in setting treatment goals for joint surgery and rehabilitation in established RA patients.

Objective: To explore the characteristics of functional impairment in patients with established rheumatoid arthritis (RA) based on the range of motion (ROM) of joints in a prospective observational study of RA patients undergoing joint surgery. Methods: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of each joint and disability in the eight HAQ-DI categories were determined using receiver operating characteristic (ROC) and logistic regression analyses. ROM cut-off values of each joint for the absence of disability in each HAQ-DI category were determined using ROC curves. Results: A total of 460 patients were enrolled and analyzed in this study. Based on ROC analysis, the ROM of each joint was significantly associated with disability in each category. After adjusting for disease activity, age, and sex, shoulder abduction had the highest independent impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion-extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR: 3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)]. Conclusions: Limited ROM of multiple joints was significantly associated with functional impairment in patients with long-standing RA. Motion in daily activity involves multiple joints, and at least two joints were independently involved in disability., Published online: 25 Jul 2017

Complete circumferential osseous extension in the acetabular rim has been reported to occur in the deep hip with pincer impingement. However, this phenomenon occasionally is observed in dysplastic hips without pincer impingement, and the degree to which this finding might or might not be associated with hip pain, and how often it occurs bilaterally among patients, are not well characterized. (1) To determine the proportion of patients with complete circumferential osseous extension in the acetabular rim using three-dimensional (3-D) CT in patients with and without hip pain who had CT scans obtained for various reasons. (2) To elucidate how often this complete circumferential osseous extension occurred bilaterally among those patients. (3) To investigate the relationship between the proportions of patients with complete circumferential osseous extension observed on CT scans among three different acetabular coverage groups: dysplasia, normal, and overcoverage. (4) To determine how often the finding of hip pain was associated with complete circumferential osseous extension. Between September 2011 to July 2016, we evaluated 3788 patients with pelvic complaints such as hip, groin, thigh, buttock, or sacroiliac joint pain. We obtained consent from 26% (992 of 3788) of them, and obtained 3-D CT scans as part of that evaluation. For the current retrospective study, we excluded patients younger than 20 years or 80 years or older (181 patients), patients who had previous hip surgery (185 patients), patients with severe osteoarthritis with Tonnis Grades 2 or 3 (301 patients), and patients who could not have an accurate lateral center-edge (LCE) angle measured owing to poor-quality radiographs (24 patients), leaving 301 patients (602 hips) for this analysis. In this study population, patients reported pain in 131 hips (22%), defined as all types of hip pain except for trauma, including activity pain, pain with sports, pain on motion, and impingement pain; the others did not report hip pain. The mean age of the patients was 56 ± 16 years, and the mean LCE angle was 26° ± 8° (range, −9° to 47°). We first determined the proportion of patients with complete circumferential osseous extension in the acetabular rim using 3-D CT for those with and without hip pain who had CT obtained for various reasons. We next elucidated how often this complete circumferential osseous extension occurred bilaterally among the patients, and finally we investigated the relationship between the proportion of patients with complete circumferential osseous extension observed on CT scans among the three groups: dysplasia (defined as LCE angles of 22° or smaller), normal, and overcoverage (defined as LCE angles of 34° or larger) groups. We finally determined how often the finding was associated with hip pain attributable to complete circumferential osseous extension. The proportion of patients with complete circumferential osseous extension was 6% (18 of 301 patients). Eighty-nine percent (16 of 18) of the patients had bilateral complete circumferential osseous extension. There were no differences in the proportions of patients with complete circumferential osseous extension among the three groups: 5.3% (odds ratio [OR], 1.02; 95% CI, 0.45-2.31; p = 0.97), 5.3%, and 7.4% (OR, 0.70; 95% CI, 0.28-1.73; p = 0.44) in the dysplasia, normal, and overcoverage groups, respectively, with the numbers available. Eighteen percent (six of 34) of the hips with complete circumferential osseous extension had pain. Complete circumferential osseous extension in the acetabular rim is relatively uncommon. When it occurs, it usually is bilateral, it occurs regardless of acetabular coverage, and it is associated with pain in a minority of patients. Level III, prognostic study.

Objective. To clarify the obstacles preventing the implementation of the treat-to-target (T2T) strategy for rheumatoid arthritis (RA) in clinical practice. Methods. A total of 301 rheumatologists in Japan completed a questionnaire. In the first section, participants were indirectly questioned on the implementation of basic components of T2T, and in the second section, participants were directly questioned on their level of agreement and application. Results. Although nearly all participants set treatment targets for the majority of RA patients with moderate to high disease activity, the proportion who set clinical remission as their target was 59%, with only 45% of these using composite measures. The proportion of participants who monitored X-rays and Health Assessment Questionnaires for all their patients was 44% and 14%, respectively. The proportion of participants who did not discuss treatment strategies was 44%, with approximately half of these reasoning that this was due to a proportion of patients having a lack of understanding of the treatment strategy or inability to make decisions. When participants were directly questioned, there was a high level of agreement with the T2T recommendations. Conclusion. Although there was a high level of agreement with the T2T recommendations, major obstacles preventing its full implementation still remain.

Objectives. This study aimed to evaluate the clinical safety and wear-resistance of the novel highly cross-linked polyethylene (HXLPE) acetabular liner with surface grafting of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) at 3 years after total hip replacement (THR).Methods. Eighty consecutive patients underwent cementless THR using a 26-mm diameter cobalt–chromium–molybdenum alloy femoral head and a PMPC-grafted HXLPE liner for the bearing couplings. We evaluated the clinical and radiographic outcomes of 76 patients at 3 years after the index surgery.Results. The clinical results at 3 years were equivalent to a Harris hip score of 95.6 points. No adverse events were associated with the implanted PMPC-grafted HXLPE liner, and no periprosthetic osteolysis was detected. The mean femoral head penetration rate was 0.002 mm/year, representing marked reduction compared with other HXLPE liners.Conclusions. A PMPC-grafted HXLPE liner is a safe option in THR and probably reduces the generation of ...

To describe an exceedingly rare case of tumor-induced osteomalacia (TIO) caused by a benign phosphaturic mesenchymal tumor that recurred after two surgical resections at two different medical institutions.A 69-year-old man complained of a 3-year history of persistent whole body pain and presented with hypophosphatemia, elevated serum levels of bone-specific alkaline phosphatase and fibroblast growth factor-23 (FGF-23), and multiple fractures. The patient was suspected of having TIO. We conducted the following diagnostic modalities considered useful to detect the tumor: serum FGF-23 level measurement in the extremities, positron emission tomography (PET)-computed tomography (CT),and magnetic resonance imaging (MRI).The causative tumor could be detected in the right humerus not by venous catheterization for serum FGF-23 level measurement but by the combination of PET-CT and MRI. The authors, who had successfully treated two patients with TIO, visually confirmed the absence of any tumor residue during tumorectomy. Nevertheless, the tumor recurred after surgery. The residual tumor could be localized in the right humerus not by PET-CT but by the combination of superficial venous sampling at 10 sites and MRI. The residual tumor recurred after the second tumorectomy at another hospital. This patient indicates that the possibility--a benign causative tumor may not be completely resected by surgery--cannot be ruled out thoroughly.Superficial venous sampling at multiple sites may be a surrogate for venous catheterization. Patients with TIO should be meticulously followed-up after surgery to detect any residual tumor by periodic biochemical monitoring and by imaging modalities accordingly.

Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs.SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22 HKDMs were examined after stimulation with tumour necrosis factor α (TNF-α) in RASFs and OASFs.The gene expression of the 12 HKMTs, including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4, DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36, H3K79, or H4K20 was higher after TNFα stimulation in RASFs vs. OASFs. The gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFα stimulation in RASFs vs. OASFs.The study findings suggest that the HKM-modifying enzymes are involved in the alteration of HKM, which results in changes in the gene expression of RASFs.

To analyze cervical spondylotic myelopathy (CSM) predictive factors in patients with lumbar spinal stenosis (LSS). Two hundred thirty-seven patients who visited for low back pain, lower limb pain and/or lower limb numbness and who were diagnosed with LSS were enrolled in this study. The ratio of males to females was 117–120, and the mean age was 68.8 years (range 45–87 years). LSS and CSM were diagnosed by characteristic symptoms, physical findings and MRI. We examined gender, age, Torg-Pavlov ratio (TPR), spondylolisthesis or spondylosis, LSS symptom types and number of stenosis segments with LSS to clarify predictive factors for CSM. There were 21 (8.86%) patients with coexistent CSM among 237 LSS patients. CSM morbidity was significantly more common among males compared with females. TPR was 0.71 ± 0.09 in the CSM patients and 0.81 ± 0.10 in the non-CSM patients. TPR of the CSM patients was significantly smaller than that of the non-CSM patients. We analyzed to determine the predictive factors of CSM and TPR was identified. The predictive value of TPR for CSM was 0.78. Torg-Pavlov ratio was the most important predictive factor of CSM in patients with LSS.

Since biologic agents were introduced to treat rheumatoid arthritis (RA) in 2003, the number of orthopedic surgical procedures under treatment with biologic agents has been increasing in Japan. However, whether biologic agents cause an increase in the prevalence of postoperative complications is as yet unknown. The Committee on Arthritis of the Japanese Orthopedic Association investigated the prevalence of postoperative complications in patients with RA in teaching hospitals in Japan.Between January 2004 and November 2008, surveillance forms about medications and surgical procedures in patients with RA were sent to 2,019 teaching hospitals. Data were analyzed by the Rheumatoid Arthritis Committee.Biologic agents were administered to RA patients in 632 of 1,245 hospitals (50.8%); 430 of the 1,245 hospitals (34.5%) used surgical intervention under treatment with biologic agents. The number of surgical procedures under treatment with biologic agents was 3,468, and the prevalence of infection was 1.3% (46 cases). The prevalence of infection was 1.0% (567 procedures) in 56,339 procedures under treatment with nonbiologic disease-modifying anti-rheumatic drugs. There were no significant differences between biological and nonbiological treatment groups with respect to the prevalence of infection. In the joint arthroplasty group, the number of procedures under biological and nonbiological treatment was 1,626 and 29,903, and the prevalence of infection was 2.1% (34 procedures) and 1.0% (298 procedures), respectively. There was a significant difference between groups. The odds ratio was 2.12 (95% confidence interval 1.48-3.03, P0.0001).The chance of having biological treatment with joint arthroplasty was more than twofold greater in patients with surgical-site infections compared with those treated with nonbiologic agents. Caution is required for surgical procedure, perioperative course, and obtaining consent for joint arthroplasty for patients with RA undergoing surgery under biological agents.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues. Constitutively activated mutants of a bone morphogenetic protein (BMP) receptor, ALK2, have been identified in patients with FOP. Recently, a novel ALK2 mutation, L196P, was found in the most benign case of FOP reported thus far. In the present study, we examined the biological activities of ALK2(L196P) in vitro. Over-expression of ALK2(L196P) induced BMP-specific activities, including the suppression of myogenesis, the induction of alkaline phosphatase activity, increased BMP-specific luciferase reporter activity, and increased phosphorylation of Smad1/5 but not Erk1/2 or p38. The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP. ALK2(L196P) was equally or more resistant to inhibitors in comparison to ALK2(R206H). These findings suggest that ALK2(L196P) is an activated BMP receptor equivalent to ALK2(R206H) and that ALK2(L196P) activity may be suppressed in vivo by a novel molecular mechanism in patients with this mutation.

Background Although several devices for meniscal repairs have become available, a successful outcome is ultimately due to a healed meniscus on the clinical findings. The authors assessed the repair integrity after meniscal repair with the FasT-Fix device using second-look arthroscopy. Hypothesis Meniscal repair with the FasT-Fix will lead to arthroscopically evident healing, but some menisci will show incomplete healing even in clinically successful cases and have newly formed injuries on the meniscal substance resulting from the path of the implant. Study Design Case series; Level of evidence, 4. Methods Sixty-five consecutive patients were studied, in whom 84 menisci were subjected to all-inside meniscal repair with the FasT-Fix device in conjunction with anterior cruciate ligament reconstruction. Repair was only performed on longitudinal or double longitudinal tears within the red-red or red-white zone. The repaired menisci were evaluated by second-look arthroscopy at the time of staged hardware removal after anterior cruciate ligament reconstruction. Results Sixty-two meniscal tears in 46 patients were available for this study. Eight patients were found to be symptomatic and considered to be clinical failures. The clinical success rate was 83%. At second-look arthroscopy, 46 tears (74%) were healed, 9 (15%) were healed incompletely, and 7 (11%) had failed. In the failed menisci,1 had meniscal symptoms, while the other 6 were asymptomatic. In the 9 menisci with incomplete healing, 3 were associated with nonspecific knee pain but none showed meniscal symptoms. Newly formed injuries, which occurred in an area different from the original repair site, were confirmed on the surface of 19 menisci (35%) among the healed and incompletely healed menisci. Thirty menisci (48%) displayed successful and complete healing of the original tear site without newly formed tears. Conclusion Meniscal repair with the FasT-Fix in conjunction with anterior cruciate ligament reconstruction resulted in complete healing in 74% of cases. Eighty-three percent of menisci were symptom-free regardless of meniscal integrity. Even when the menisci repaired are asymptomatic and considered to be a clinical success, however, there may be newly formed injuries.

To reduce the production of wear particles and subsequent aseptic loosening, we created a human articular cartilage-mimicked surface for a highly cross-linked polyethylene liner, whose surface grafted layer consisted of a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine). Although our previous in vitro findings showed that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted particles were biologically inert and caused no subsequent bone resorptive responses, and poly(2-methacryloyloxyethyl phosphorylcholine) grafting markedly decreased wear in hip joint simulator tests, the clinical safety, and in vivo wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners remained open to question. Therefore, in the present study, we evaluated clinical and radiographic outcomes of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners 5 years subsequent to total hip replacement in 68 consecutive patients. No reoperation was required for any reason, and no adverse events were associated with the implanted liners. The average Harris Hip Score increased from 38.6 preoperatively to 96.5 5 years postoperatively, and health-related quality of life, as indicated by the Short Form 36 Health Survey, improved. Radiographic analyses showed no periprosthetic osteolysis or implant migration. Between 1 and 5 years postoperatively, the mean steady-state wear rate was 0.002 mm/year, which represented a marked reduction relative to other highly cross-linked polyethylene liners, and appeared to be unaffected by patient-related or surgical factors. Although longer follow up is required, poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners improved mid-term clinical outcomes. The clinical safety and wear-resistance results are encouraging with respect to the improvement of long-term clinical outcomes with poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2007-2016, 2017.

Dear Editor, In clinical practice, skeletal fragility can be estimated, for example, by dual-energy X-ray absorptiometry (DXA) as areal bone mineral density (BMD) at the femoral neck, hip axis length, and trabecular bone score at the lumbar spine, while aging is an independent strong risk factor for fracture as well as falling and plays a key role in the FRAX-based assessment and intervention thresholds [1–6]. In contrast, the skeleton has a natural homeostatic system known asWolff’s law, indicating that mechanical environment is the primary determinant of bone strength. Here, we would like to discuss the age-related bone fragility on the basis of skeletal adaptation to mechanical loading. Habitual physical activity normally results in “elastic” deformation (strain) of the skeleton. The uniformity in peak strain magnitudes and maximum strain rates on bone surfaces during locomotion in various animals, including humans, confirms skeletal adaptation to mechanical strain-related stimulus called the mechanostat [7], and several lines of evidence in adult animals and humans have shown that the mechanical strain-related feedback control acts continuously throughout the physiologic range [8–12]. Thus, bone fragility with age is associated with the reduction of physical activity that would cause decreases in peak strain magnitudes and maximum strain rates, both of which are critical factors of the mechanostat, though the number of cycles of mechanical loading required to maximally stimulate bone is surprisingly small [7]. In addition, aging impairs skeletal response to mechanical loading [12–16]; although osteocytic canalicular networks would deteriorate with age [17], the response could be relatively maintained in osteocytes compared to osteoblasts [14]. Mechanical loading can stimulate bone formation and inhibit bone resorption, while aging has the opposite effects [18] and its influence on the response might be stronger in bone formation [15]. Finally, collagen cross-linking is a major post-translational modification of collagen, and aging causes a decrease in enzymatic collagen cross-links and an increase in non-enzymatic collagen cross-links in the skeleton [19]. There is a yield force at which a bone begins to deform plastically, and skeletal adaptation to mechanical strain can be expected to work against the pre-yield “elastic” deformation but not to the post-yield “plastic” deformation. Recently, it has been suggested that skeletal fragility in diabetes, for instance, could be linked to the failure of the mechanostat due to the impairment of bone tissue properties associated with collagen crosslinking that would affect the post-yield “plastic” deformation [20]. This is a possible Achilles heel of the mechanostat and appears to be one significant cause of the age-related bone fragility. A significant age-related increase in fracture risk independently of areal BMD [1–3] might partly result from the failure of natural homeostatic system due to the impaired bone tissue properties as mentioned above, in addition to an involvement of falling [6]. Skeletal fragility is determined not only by areal BMD but also by other factors including bone quality, and it is therefore important to note that osteoporosis defined by areal BMD alone and bone fragility are two different terms and thus should not be used interchangeably. * Toshihiro Sugiyama tsugiym@saitama-med.ac.jp

Background Several kinds of thermally processed hydroxyapatite have been commonly used for bone defects due to bone diseases or fractures instead of autologous bone grafts. However, these materials do not change in form during surgery and are not absorbed over a long period. To overcome this disadvantage, calcium phosphate bone cements (CPCs) have been developed and are already in use in clinical cases. These materials have merit in that to be formed in situ they are injectable and absorbable, but there are still problems with their handling and their hardening properties. A newly developed CPC called XSB-671D hardens earlier and is more resistant to body fluids than other CPCs. The purpose of this article is to verify the effectiveness, safety and usefulness of this CPC (XSB- 671D) as a bone defect filler. Methods We conducted clinical trials at five medical institutions based on a unified protocol in a total of 75 cases (30 males, 45 females). We observed the postoperative constitutional symptoms and local symptoms of the filling sites. The effectiveness of this material was evaluated by radiographs of the filled sites, and blood and urine were examined to evaluate any adverse effects. Results The ratio of the cases determined to be “effective” or “better” among the 74 cases we found qualified was 97.3%, and XSB-671D was confirmed to be a highly effective material with beneficial effects of biocompatibility and osteoconduction as a bone defect filler. Additionally, there were no adverse effects caused by XSB-671D except one local skin reaction, which disappeared 2 weeks later; its safety was also thus verified. Conclusions We conclude that effective, safe treatment is possible using XSB-671D in cases requiring filling of a bone defect as well as those with serious osteoporosis.

The receptor activator of NF-kappaB ligand (RANKL), a critical regulator of osteoclastogenesis, is synthesized as a membrane-anchored protein and cleaved into a soluble form by ectodomain shedding. We developed an assay system to identify molecules regulating the RANKL shedding. Using this system, we found that a splice variant of Ca2+-promoted Ras inactivator (CAPRI), deltaCAPRI, which is expressed in primary osteoblasts, promoted the RANKL shedding. The wild type CAPRI is a member of the Ras GTPase-activating protein (GAP) family and suppresses Ca2+-dependent Ras activation, whereas deltaCAPRI, which lacks one exon in the GAP-related domain, activated the Ras pathway. Overexpression of deltaCAPRI or a constitutive active form of Ras up-regulated the expression level of matrix-metalloproteinase 14 (MMP14), which directly cleaves the ectodomain of RANKL, whereas Erk activation by expressing the constitutive active Mek1 did not affect the MMP14 expression or RANKL shedding. These results suggest that deltaCAPRI is a possible regulator of RANKL shedding by modulating MMP14 expression through Ras signaling cascades other than the Erk pathway.

Objective Chondromodulin I (ChM-I), a cartilage matrix protein, promotes the growth and proteoglycan synthesis of chondrocytes. However, it also inhibits angiogenesis. Since ChM-I is expressed not only in cartilage, but also in the thymus, we investigated the modulation of T cell function by ChM-I to assess its therapeutic potential in rheumatoid arthritis (RA). Methods The localization of ChM-I expression in mouse thymus tissue was examined by in situ hybridization. The proliferative response of peripheral blood T cells and synovial cells obtained from patients with RA was evaluated by 3H-thymidine incorporation assay. The effects of ChM-I were examined using recombinant human ChM-I (rHuChM-I). Modulation of the antigen-specific immune response was evaluated by the recall response of splenic T cells and the delayed-type hypersensitivity response induced in the ear of mice primed with ovalbumin (OVA). Antigen-induced arthritis (AIA) was induced in mice by injecting methylated bovine serum albumin into the ankle joints 2 weeks after the priming. Results ChM-I was expressed in the cortex of the thymus. Recombinant human ChM-I suppressed the proliferative response of mouse splenic T cells and human peripheral blood T cells stimulated with anti-CD3/CD28 antibodies, in a dose-dependent manner. Production of interleukin-2 was decreased in rHuChM-I–treated mouse CD4 T cells. Ten micrograms of rHuChM-I injected intraperitoneally into OVA-primed mice suppressed the induction of the antigen-specific immune response. Finally, rHuChM-I suppressed the development of AIA, and also suppressed the proliferation of synovial cells prepared from the joints of patients with RA. Conclusion These results suggest that ChM-I suppresses T cell responses and synovial cell proliferation, implying that this cartilage matrix protein has a therapeutic potential in RA.

Synovial fibroblasts (SFs) produce matrix-degrading enzymes that cause joint destruction in rheumatoid arthritis (RA). Epigenetic mechanisms play a pivotal role in autoimmune diseases. This study was undertaken to elucidate the epigenetic mechanism that regulates the transcription of matrix metalloproteinases (MMPs) in RASFs.MMP gene expression and histone methylation profiles in the MMP promoters were examined in RASFs. The effect of WD repeat domain 5 (WDR5) silencing on histone methylation and MMP gene expression in RASFs was analyzed. MMP gene expression, surface expression of the interleukin-6 (IL-6) receptor, phosphorylation of STAT-3, and binding of STAT-3 in the MMP promoters were investigated in RASFs stimulated with IL-6.The MMP-1, MMP-3, MMP-9, and MMP-13 genes were actively transcribed in RASFs. Correspondingly, the level of histone H3 trimethylated at lysine 4 (H3K4me3) was elevated, whereas that of H3K27me3 was suppressed in the MMP promoters in RASFs. The decrease in H3K4me3 via WDR5 small interfering RNA reduced the levels of messenger RNA for MMP-1, MMP-3, MMP-9, and MMP-13 in RASFs. Interestingly, IL-6 signaling significantly increased the expression of MMP-1, MMP-3, and MMP-13, but not MMP-9, in RASFs. Although the IL-6 signaling pathway was similarly active in RASFs and osteoarthritis SFs, STAT-3 bound to the MMP-1, MMP-3, and MMP-13 promoters, but not the MMP-9 promoter, after IL-6 stimulation in RASFs.Our findings indicate that histone methylation and STAT-3 regulate spontaneous and IL-6-induced MMP gene activation in RASFs. The combination of chromatin structure and transcription factors may regulate distinct arthritogenic properties of RASFs.

The skeleton normally responds to mechanical environment to maintain the resulting elastic deformation (strain) of bone, while increased bone strength by an osteoporosis drug results in decreased bone strain. Thus, it can be hypothesized that the effect of osteoporosis therapy is limited by natural homeostatic system in the skeleton. This logic is consistent with the fact that there exists a powerful effect that returns bone mass to its pre-treatment level after the withdrawal of treatment with osteoporosis agents. The present hypothesis provides a new significant insight into the mechanisms by which osteoporosis drugs improve bone fragility. Here we briefly discuss the effects of teriparatide, romosozumab, and odanacatib on bones in animals and humans.

Accumulating evidence indicates that epigenetic aberrations have a role in the pathogenesis of rheumatoid arthritis (RA). However, reports on histone modifications are as yet quite limited in RA. Interleukin (IL)-6 is an inflammatory cytokine which is known to be involved in the pathogenesis of RA. Here we report the role of histone modifications in elevated IL-6 production in RA synovial fibroblasts (SFs). The level of histone H3 acetylation (H3ac) in the IL-6 promoter was significantly higher in RASFs than osteoarthritis (OA) SFs. This suggests that chromatin structure is in an open or loose state in the IL-6 promoter in RASFs. Furthermore, curcumin, a histone acetyltransferase (HAT) inhibitor, significantly reduced the level of H3ac in the IL-6 promoter, as well as IL-6 mRNA expression and IL-6 protein secretion by RASFs. Taken together, it is suggested that hyperacetylation of histone H3 in the IL-6 promoter induces the increase in IL-6 production by RASFs and thereby participates in the pathogenesis of RA.

Synovial fibroblasts, established in culture from patients with RA, were treated with proinflammatory cytokines and prostaglandin E(2) (PGE(2)) for 24 h. These cells enhanced the production and the messenger RNA expression of PTH-related peptide (PTHrP) using proinflammatory cytokines, such as interleukin (IL)-1alpha, tumor necrosis factor-alpha without the coordination of other cytokines. In addition, PGE(2) which has been induced with IL-1, also enhanced the production of PTHrP. The IL-1alpha-induced PTHrP production was inhibited by PG H synthetase (Cox) inhibitors, indomethacin, and also by Cox-2 inhibitor, NS398. The synovial fibroblasts expressed PGE(2) receptor subtypes, EP2, EP3, EP4, but not EP1, as detected by RT-PCR. Of the PGE(2) receptor agonists, EP4 agonist showed the most marked induction of PTHrP, and EP2 agonist partly induced the production. However, these PGE(2) receptors were not induced by the treatment with IL-1alpha and PGE(2). These results suggest that induction of PGE(2) by IL-1alpha may be an important component of the PTHrP production of the inflammatory process in synovial tissues from patients with RA. These findings are the first to demonstrate that PGE(2) stimulates PTHrP production, which is mediated mostly by EP2 and EP4 receptors.

We examined the production of substance P (SP) in synovial fibroblasts derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunoreactive SP was observed in non-stimulated RA fibroblasts. The expression of beta-preprotachykinin-A (beta-PPT-A) mRNA was confirmed by reverse transcription-polymerase chain reaction analysis. SP contents in culture medium were increased by treatment of RA fibroblasts with transforming growth factor-beta (TGFbeta) (10 ng/ml). Levels of SP release were elevated at 12 h after TGFbeta stimulation whereas the expression of beta-PPT-A mRNA was enhanced at 3 h. Furthermore, SP production in response to TGFbeta was dose-dependently enhanced by basic fibroblast growth factor (bFGF). OA fibroblasts also significantly released SP in the presence of TGFbeta (10 ng/ml) plus bFGF (50 ng/ml). These results suggest that SP produced by synovial fibroblasts may participate in joint diseases.

Involuted intraosseous lipoma with extensive fat necrosis resulting in cyst formation (Milgram stage III) is distinguishable from lesions without necrosis (stage I) or lesions with focal fat necrosis (stage II), based on differences in signal intensity on magnetic resonance imaging (MRI). Fat tissue has a high signal intensity on both T1- and T2-weighted MR images, whereas the extensive fat necrosis that results in cyst formation shows high signal intensity on T2-weighted images and low intensity on T1-weighted images. We report a patient in whom an intraosseous lipoma with high signal intensity on both T1- and T2-weighted MRI was found to be extensively involuted on histopathologic examination. Intraosseous lipoma appears to undergo spontaneous involution. In some patients, therefore, surgical excision may not be necessary. A correct preoperative diagnosis should reduce the necessity for a biopsy or surgery. Although lesions classified as stage I or II are easily identified by MRI, those of stage III are difficult to diagnose preoperatively by this method.

Busulfan (BU) is an alkylating agent that is used in alter-native conditioning regimen for total body irradiation(TBI) before stem cell transplantation (SCT) especially toreduce its late toxicities such as growth impairment andsecond malignancy. Because its therapeutic window isnarrow and, inter- and intra-patient variability of plasmaexposure is wide in case of conventional oral formulation,therapeutic drug monitoring (TDM) is recommended toavoid severe toxicity or rejection, especially in youngerpatients in which its variability is much more [1, 2]. ByTDM, BU dose should be adjusted so that calculatedconcentration at steady state (Css) or area under the curve(AUC) is in the range of 600–900 ng/ml or 900–1500 mmol min/L. In this context, introduction of intra-venous formulation is expected to resolve these problems.For small children, recommended dose for intravenousformulation has been reported [3, 4]. However, there is arecent report that emphasizes the necessity of TDM even inintravenous formulation [5]. In this background, weinvestigated allogeneic SCT cases with BU regimen in ourinstitute retrospectively.Since 1995, 34 patients received allogeneic hematopoi-etic SCT by using BU regimen in our pediatric section.Former 29 patients received BU orally (four doses per dayfor four consecutive days; p.o.BU group), and latter fivepatients received BU intravenously (2-h infusion every 6 hfor four consecutive days; i.v.BU group).For pharmacokinetic (PK) analysis, blood samples wereobtained 1, 2, 3, 4, and 6 h after medication of BU. Inp.o.BU group, PK analysis were performed in the last 10cases, in which test dose (0.5–0.7 mg/kg) was performed2 weeks before conditioning chemotherapy, and dose wasadjusted according to the result of PK analysis up to themaximal dose of 2 mg/kg/dose (Table 1). PK analysis wasalso performed for the initial dose, and dose was adjustedin fourth day (13th dose) in case calculated Css of BUexceeded the range of 600–900 ng/ml [Only in case 3, dosewas reduced from 1.8 to 1.1 mg/kg/dose.]. In i.v.BU group,BU was administered according to the recommendation [3,4], and blood sample was taken and stored for later PKanalysis except for the last case (case 15). In case 15, testdose was performed, and dose was reduced from 1.0 to0.8 mg/kg/dose. Informed consent was obtained from all ofthe patients or patient’s guardians before conducting thetest dose. Also, we have approval for this procedure fromour IRB.Among 15 cases in which PK analysis was performed(Table 1), graft rejection was observed only in one case(case 5) of p.o.BU group, which was a patient withhemophagocytic lymphohistiocytosis. No hepatic veno-occlusive disease (HVOD) occurred in p.o.BU group, butwas observed in two out of five i.v. cases, in which onecase (case 13) had severe HVOD and died 60 days afterSCT because of hepatic failure. In case 13, the patientreceived first SCT from HLA identical sibling with TBI(12 Gy) and cyclophosphamide (60 mg/kg 9 2 days) reg-imen. After relapse in 3 months, he was treated withHperCVAD plus imatinib chemotherapy [6] and received

A spontaneous subcapital femoral neck fracture is an uncommon complication of a healed intertrochanteric hip fracture. To determine the etiology of this complication, 274 patients who had been treated for intertrochanteric hip fractures were followed up over an 8-year period from June 1988 to June 1996. We found 7 fractures of the subcapital femoral neck without a history of a trauma. The remaining 267 patients were defined as the control group. All seven patients with fractures of the subcapital femoral neck were women, and their average age at the time of compression hip screw (CHS) fixation was 83 years (range 74–92 years). The subcapital fractures occurred between 4 and 36 months after CHS fixation. The difference in the Singh index between the patient and control groups was statistically significant (P < 0.01). However, with regard to the position of the screw, spinal score, age, ambulatory ability, height, weight, and intertrochanteric fracture type (Jensen type), the differences between the patient and control groups were not statistically significant. Based on our findings, we conclude that a high grade of osteoporosis is the most important predisposing factor in the spontaneous development of a subcapital femoral neck fracture after a healed intertrochanteric hip fracture.

We have explored the use of adenovirus vector-mediated gene transfer to introduce foreign genes into osteoclasts, terminally differentiated cells responsible for bone resorption. A replication-deficient adenovirus vector that contains a reporter gene encoding beta-galactosidase efficiently infected human osteoclast-like cells (OCLs) derived from human giant cell tumors and mouse OCLs formed in vitro. We then constructed an adenovirus vector carrying human epidermal growth factor receptor (EGFR) cDNA (Ax1CAhEGFR) and introduced the EGFR gene into mouse OCLs. Clear induction of EGF receptor was detected in Ax1CAhEGFR-infected OCLs (EGFR-OCLs) by immunocytochemistry and immunoblotting, and EGF stimulation induced rapid tyrosine phosphorylation of several proteins including EGF receptor itself. Large vacuoles appeared in EGFR-OCLs in response to EGF treatment, and pit-forming activity by EGFR-OCLs was dose-dependently suppressed by recombinant human EGF. In addition, survival of EGFR-OCLs was prolonged by EGF. No expression of EGF receptor or effects of EGF were observed in noninfected OCLs or control vector-infected OCLs. These results suggest that adenoviral vectors are useful for modulating osteoclast function by introducing foreign genes into osteoclasts and that they will be a good means of gene therapy of metabolic bone diseases.

Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH) 2 vitaminD 3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis.

Bone remodeling is only dynamic feature which observed in adult bones except during fracture healing. Patients of bone metabolic diseases show abnormal characteristics in bone remodeling. Observation of structural and÷or dynamic changes of packets in the cancellous bone is useful for understanding a status of bone remodeling. Histomorphometric analysis of bone from iliac biopsy is established methods for clarifying the etiology, pathogenesis, and the effects of treatments. This chapter contains the way for understanding dynamic parameters, age and disease related changes of parameters, and the methods of the iliac bone biopsy.

Study Design. This in vitro analysis defines biomechanical properties of the Triumph Lumbar Disc (TLD) for posterolateral lumbar disc arthroplasty. Objectives. To quantify segmental kinematics afforded by the TLD, determine whether intervertebral positional changes of the device affect spinal kinematics, and compare kinematics following TLD reconstruction with historical CHARITE data. Summary of Background Data. As an alternative to arthrodesis, total disc arthroplasty serves to restore the biomechanical properties of the spine. However, there are kinematic and clinical concerns regarding posterior lumbar column destabilization and reconstruction using motion-preserving technology. Methods. Seven human lumbosacral spines were biomechanically evaluated under the following conditions: (1) Intact; (2) Unilateral facetectomy; (3) Facetectomy and discectomy; (4) TLD-posterior; (5) TLD-central; (6) TLD-anterior. Centers of intervertebral rotation (COR) and intradiscal pressures were compared at the operative/adjacent levels. Results. In axial rotation, L4-L5 range of motion (ROM) increased to 110% ± 15.3% following unilateral facetectomy and 134.3% ± 26.9% following facet/discectomy. Implanting the TLD in 3 positions—posterior, central, and anterior-demonstrated no significant differences in ROM (P > 0.05). Trends were similar in flexion/extension and lateral bending. The neutral zone increased under the facet/discectomy condition and TLD reconstructions compared to the intact condition (P < 0.05). CORs were dispersed at the operative level following destabilization. TLD in posterior and central positions restored loci to near the intact condition, whereas the anterior position produced more diffuse CORs. Adjacent level intradiscal pressures decreased in flexion-extension following destabilization and reconstruction. Conclusion. Axial rotation ROM following TLD reconstruction (central position) was 131.5% of intact, compared to historical controls for the CHARITE device (162.0%). This indicates that lumbar disc arthroplasty performed using a posterolateral approach may offer biomechanical advantages over the anterior approach. Moreover, this approach may minimize surgical complications and allow simultaneous decompression of the neural elements. Intervertebral positional changes of the TLD were not shown to affect spinal kinematics.

The effectiveness of percutaneous vertebroplasty for osteoporotic vertebral pseudarthrosis with delayed-onset paraplegia has not been reported. We performed vertebroplasty for such patients and tried to investigate the effectiveness of this surgery.We studied 11 patients (2001-2007) treated with percutaneous vertebroplasty for osteoporotic vertebral pseudarthrosis with delayed-onset paraplegia. The mean age of the patients was 71.9 ± 5.2 years and the affected vertebrae were located in the thoracolumbar junction. The mean period between the onset of motor weakness and the day of the surgery was 9.5 ± 5.7 weeks. Vertebroplasty was performed by filling the intravertebral cleft with polymethylmethacrylate. The clinical course was estimated using the Denis pain scale, the Eastern Cooperative Oncology Group performance status scale and the modified Medical Research Council grade before the surgery, 0, 1, 3, 6 months and 1 year following the surgery, and at the latest follow-up visit. The instability angle and local kyphotic angle were evaluated with X-rays.Significant improvements were observed in the pain scale in all patients, as they did not experience severe pain, and the performance status following the surgery. These conditions continued until the final clinical examination. Most patients had motor weakness, with a preoperative manual motor test score of 0-3, which gradually improved to 4-5 over the examination period. The stabilities of the affected vertebrae were confirmed on imaging at the final examination. Kyphotic changes were initially realigned, but a correction loss occurred in 7 of the 11 patients as a result of adjacent vertebral fractures. Increase in kyphosis following the surgery did not affect the muscle strength recovery. Bridging callus formations were observed around the affected vertebrae within 6 months in all cases.Percutaneous vertebroplasty for vertebral pseudarthrosis with delayed-onset paraplegia is effective for recovering muscle strength, improving performance status and relief from pain, despite local kyphosis.

The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2–4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2–4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2–4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.