AimsAcridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases.MethodsWe used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.ResultsThe viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer.ConclusionAO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo.Cite this article: Bone Joint Res 2022;11(10):715–722.

Patients 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. Methods Data 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 pres-entation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study. Results A 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. Conclusion Using 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 under-went PE. Reconstruction may be necessary when additional excision is performed.

Background: Hemi-resurfacing arthroplasty (Hemi) and metal-on-metal hip resurfacing arthroplasty (HRA) are alternatives to conventional total hip arthroplasty (THA) for patients with osteonecrosis of the femoral head (ONFH). Mid- to long-term results were evaluated.Methods: Twenty-three hips with osteonecrosis of the femoral head were treated, using Hemi in 12 and HRA in 11. Mean follow-up was 13.8 years in the Hemi group and 8.7 years in the HRA group. Mid- to long-term clinical scores, radiographic results, and survivorship were reviewed retrospectively.Results: In the Hemi group, 8 hips were revised to THA due to migration. In the HRA group, 1 hip was revised due to adverse local tissue reaction. No evidence of any femoral loosening or neck narrowing was seen in either group. Clinical score was superior with HRA compared to Hemi. Ten-year survival rates were 64.2% and 90.9% in the Hemi and HRA groups, respectively. Survival rate in the Hemi group dropped to 22.0% at 14 years.Conclusion: Hemi did not represent a better alternative to THA for patients with ONFH. HRA could offer attractive indications for 10 years.

Aims Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826.

Background Systemic sclerosis (SSc) is a connective tissue disease that develops sclerotic changes in the skin and visceral organs. SSc is a disease of uncertain etiology, and is characterised by fibrotic changes. Pulmonary, cardiac, gastrointestinal, and renal complications contribute to patient morbidity and decreased survival1. And patients present with stiffness of the limbs because of sclerosis and joint swelling in the skin and periarticular connective tissues. Interleukin-6 (IL-6) is a pleiotropic factor that plays a major role in inflammation; furthermore, IL-6 overexpression and pathogenicity in SSc have been demonstrated2. IL-6 expression is reportedly high in both the skin and serum of SSc patients3, and its elevation depends on the skin score4. And it is a candidate factor that can reproduce the pathological conditions of SSc as well as RA. Objectives We report the cases of rheumatoid arthritis (RA) patients with SSc who was administered anti-interleukin-6 receptor antibody tocilizumab (TCZ). Methods Two RA with refractory SSc patients were administered tocilizumab at 162 mg/kg twice a month for 12 months. RA disease activity is evaluated by DAS28-ESR and CDAI. Skin condition of SSc is evaluated by pinching the skin according to the modified Rodnan total skin score (mRTSS). Results They were both female, and age at the time of SSc diagnosis was 74 (patient 1) and 51 (patient 2) years old. The time lapse since SSc diagnosis was at first visit and 14 years, respectively. And it since RA diagnosis was 14 years and 6 years, respectively. Tocilizumab was administered at 162 mg every 2 weeks, which is equal to the dosage used for RA. Administration of prednisolone at 5 mg/day and DMARDs were continued. Overall, TCZ was well tolerated, and both patients experienced a general improvement in coping with normal daily activities. During the 12 month tocilizumab therapy, both RA disease activity and mRTSS decreased. The patient global assessment improved by 70 (75 to 5) and 44 (68 to 24) in patients 1 and 2 in 12 months, respectively. In RA disease activity, DAS28 decreased from 5.66 to 1.73 in 12 months in patient 1 and 7.14 to 4.43 in patient 2. CDAI decreased from 31.8 to 7.4 in 12 months in patient 1 and 34.6 to 10.7 in patient 2. Skin thickness evaluated with the 17 site modified Rodnan skin score improved in patient 1 (from 23 to 2) and patient 2 (from 15 to 8) in 12 months. Adverse reactions were observed cellulitis in right foot planter at 6 week treatment in patient 2. She did withdrawal tocilizumab for 4 week. After cure cellulitis, she continued tocilizumab treatment. Conclusions In the two cases of RA with SSc that we report here, softening of the skin was observed during the treatment with tocilizumab. Tocilizumab may be effective against RA and SSc for which conventional treatment is inadequate. References [1] Best Pract Res Clin Rheumatol2010;24:857–69 [2] Inter J Rheumatol2011;2011:721608 [3] J Rheumatol;25:308–13 [4] J Dermatol Sci2001;27:140–6 Disclosure of Interest None declared

Category: Midfoot/Forefoot Introduction/Purpose: Hallux valgus (HV) is one of the most common forefoot problems. HV is defined as a hallux valgus angle of more than twenty degrees. HV can lead to alterations of the plantar pressure pattern and clinical gait. This study examined the relationship between gait alterations and HV deformities. Methods: We examined 500 residents (161 men and 339 women; >50 years of age) of Miyagawa village in Mie, Japan in 2009, 2011 and 2013. They performed a 6-meter walk test at normal and maximum speed. We examined gait speed, the number of steps, and footprint between patients with normal (HV angle <20; n=350) and HV (HV angle >20; n=150), and between normal-to-mild (HV angle <30; n=436) and moderate-to-severe (HV angle >30; n=64). Their plantar pressure patterns were measured using a gait analyzer (Walk Way MW 1000; Anima, Tokyo, Japan, Figure.1). Statistical analyses were performed using the chi-square test according to sex and use of the hallux ball; the t-test according to age, height, and weight; and logistic regression analysis adjusted for age, sex, and height according to gait speed and the number of steps. P value less than 0.05 was considered significant. Results: With regard to the plantar pressure pattern, the percentage of subjects in the HV group who left a footprint of the hallux ball was significantly lower than that in the normal group. The percentage of subjects in the moderate-to-severe group who left a footprint of the hallux ball was even lower. Analysis of the footprint revealed that the HV group used the hallux ball significantly less during toe-off than the normal group. At both normal and maximum speed, the number of steps and gait speed did not differ significantly between the normal and HV groups. However, when we compared normal-to-mild and moderate-to-severe groups, the number of steps in the moderate-to-severe group was significantly greater than in the normal-to-mild group at maximum walking speed. Conclusion: Analysis of the footprint revealed that the percentage of subjects in the HV group who was able to use the hallux ball during toe-off was significantly less than that in the normal group. The percentage of subjects in the moderate-to-severe group who could use the hallux ball in toe-off was even lower. HV can cause footprint alterations. Moderate-to-severe HV can cause not only footprint alterations but also gait alterations, especially when walking at maximum speed.

Introduction: An analysis of the activated partial thromboplastin time (APTT) in major orthopedic surgery patients receiving edoxaban for the prevention of venous thromboembolism (VTE) was carried out. Methods: The APTT waveform was analyzed in the above patients to monitor edoxaban administration. Results: Of these 99 patients, 12 exhibited deep vein thrombosis, and 25 had massive bleeding. An increased biphasic pattern of the APTT waveform was observed after the administration of edoxaban, but there were no significant differences between the patients with and without complications. The peak times of acceleration, velocity, and 1/2 fibrin formation were significantly prolonged after the administration of edoxaban, especially in patients with massive bleeding, and were moderately correlated with the anti-Xa activity. While the heights of velocity and acceleration peak 2 were lower in patients receiving warfarin treatment than in those receiving edoxaban, the widths of these parameters were significantly longer. The height of 1/2 fibrin formation and the width of acceleration peaks 1 and 2 and the velocity were significantly increased after the administration of edoxaban. Conclusion: The peak time of the APTT waveform was significantly prolonged after the administration of edoxaban. The analysis of the APTT waveform may therefore be useful for the prediction of the risk of massive bleeding.

We reported a 69-year-old female who discontinued denosumab due to dental treatment and subsequently suffered rebound-associated vertebral fractures 10 months after the last injection. This case raised an alarm regarding the discontinuation of denosumab for dental treatment. Denosumab, a human monoclonal antibody administered by subcutaneous injection, to the best of our knowledge, is the only fully investigated inhibitor of receptor activator of nuclear factor kappa B ligand. Discontinuation of denosumab leads to bone turnover rebound and rapid bone mineral density loss. Several studies have reported rebound-associated vertebral fractures after discontinuation of denosumab. We report on a new case of rebound-associated vertebral fractures after discontinuation of denosumab. A 69-year-old female, who withdrew from denosumab treatment after 3 years due to maxillitis, presented to our hospital with severe low back pain without any history of trauma. Ten months had passed since the last injection. Magnetic resonance imaging showed five acute vertebral fractures, which appeared to be rebound-associated vertebral fractures caused by discontinuation of denosumab due to dental treatment. This case clearly demonstrates the risk of discontinuation of denosumab for dental treatment.

Background Osteoporosis may cause not only fractures but also chronic back pain in elderly women. Teriparatide (TPTD) and alendronate (ALN) are widely used in clinical for treatment of osteoporosis. Several studies have demonstrated that TPTD and ALN treatments improved skeletal pain in osteoporosis patients. Objectives We investigated the effect of TPTD and ALN on pain-related behavior in ovariectomized (OVX) mice. And we investigated expression of inflammatory cytokines treated OVX mice. Methods 8-week-old female ddY mice were OVX and assigned to 4groups; SHAM-operated mice treated with vehicle (SHAM), OVX mice treated with vehicle (OVX), OVX mice treated with TPTD (TPTD) and OVX mice treated with ALN (ALN). Mice were started treatment immediately after surgery. For 4 weeks, mice were injected subcutaneously with vehicle or 40μg/kg ALN twice a week or 40μg/kg TPTD 5 times a week. The bilateral distal femur metaphyses were analyzed three-dimensionally by μCT 4 weeks after surgery (each group; n=8). Mechanical sensitivity was tested using von Frey filaments 4 weeks after surgery. To evaluate the 50% withdrawal threshold, seven von Frey filaments with forces of 0.07, 0.16, 0.4, 0.6, 1.0, 1.4 and 2.0 g were applied to the middle of the plantar surface. Data was collected using the up-down method. To evaluate expression of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), mice were anesthetized and the bilateral hindlimb bone excised. We performed quantitative polymerase chain reaction (q-PCR) from hindlimb bone. Results μCT analysis of the distal femur metaphysis showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the OVX group than in the SHAM group, whereas trabecular separation (Tb.Sp) was significantly greater in the OVX group than in the SHAM group. In the TPTD and ALN group, BV/TV and Tb.N were significantly greater than in the OVX group, whereas Tb.Sp was significantly less than in the OVX group. And in the ALN group, BV/TV and Tb.N were significantly greater than in the TPTD group, but Tb.Sp was no significance. The 50% withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and it was significantly higher in the TPTD and ALN group than in the OVX group. And the 50% withdrawal threshold was no significance between the TPTD and ALN group. The expression levels of TNF-α was increased in the OVX group compared with those in the SHAM group. Other cytokines were not increased significantly in the OVX group. In the TPTD and ALN group, the expression levels of TNF-α was significantly degreased than the OVX group. And the expression levels of TNF-α was no significance between the TPTD and ALN group. Conclusions In this study, TPTD and ALN treatments prevented bone loss in OVX mice. Mechanical hyperalgesia in hindlimbs tended to be decreased in the OVX group compared with the TPTD and ALN group. ALN treatment was more effective in bone formation compared with TPTD treatment, whereas pain relief was no significance between TPTD and ALN treatment. These results suggest that TPTD treatment was more effective in osteoporosis patients with skeletal pain. Disclosure of Interest None declared

Background The aim of this study was to elucidate the clinical outcomes of patients with STSs who received additional excisions after unplanned excisions (UE) using data from the Bone and Soft Tissue Tumor Registry in Japan. Methods We examined 197 patients with STSs who received an additional excision after a UE. Data from 2006 to 2013 were obtained from the BSTT Registry. There were 112 men and 85 women, with a mean age of 54 years. The mean primary tumor size was 4.7 cm. Tumor depth was classified as superficial (n = 132) or deep (n = 65). Results Residual tumor cells were observed in 115 of 197 (58%) specimens at additional excision. Wide margins were achieved in 190 patients, whereas marginal or intra-lesional margins were made in seven patients. One hundred and five patients (53%) required plastic reconstructions. The 5-year disease-specific survival rate was 97.4%. Local recurrence occurred in 15 patients, and the 5-year local recurrence-free rate was 91%. Residual tumor tissue in re-excision specimens was an independent prognostic factor for local control (P = 0.04). The 5-year local recurrence-free rate was significantly worse in patients with residual tumors than in those without residual tumors. Conclusions We suggest that UEs should be avoided because they require additional excisions and, in many cases, subsequent soft tissue reconstruction. Additional excisions that are sufficiently extensive may improve local control, although patients with residual tumor tissue in re-excision specimens should be carefully followed up.

The purpose of this study was to clarify the precise effect of argatroban on the inhibition of cytokine secretion induced by thrombin on synovial cells. The efficiency of thrombin inactivation by thrombin inhibitors was evaluated in human synovial fluids SFs). In SFs from 13 osteoarthritis OA) and 11 rheumatoid arthritis RA) patients, thrombin, Factor Xa FXa), plasmin activity, IL-6, MMP-3, VEGF, and D-dimer concentrations were measured. Tissue factor TF) activity or IL-6, MMP-3, and VEGF secretion of human synovial cells with or without thrombin and argatroban were measured. The efficiency of thrombin inactivation in SFs was compared for thrombin inhibitors: argatroban, antithrombin III ATIII), or heparin cofactor II HCII). In SFs, thrombin, FXa, plasmin, D-dimer, IL-6, and MMP-3 were significantly higher in RA than in OA. In synovial cell experiments, TNF-alpha and thrombin enhanced TF activity on the cell surface, and IL-6, MMP-3, and VEGF secretion were enhanced by thrombin. Increased TF activity, and IL-6, MMP-3, and VEGF secretion induced by thrombin were inhibited by argatroban. In SFs, argatroban inactivated thrombin more effectively than ATIII or HCII. Since thrombin plays an important role in the disease activity of OA and RA, it is a potential therapeutic molecular target. Argatroban was the most effective anticoagulant to inhibit thrombin activity in SF. Intraarticular injection is ideal administration because it can deliver high dose of argatroban without high risk of systematic complication.

Some patients with osteoporosis do not respond to teriparatide treatment. Prior bisphosphonate use, lower bone turnover marker (BTMs) concentrations, and lower early increases in BTMs were significantly associated with a blunted lumbar spine (LS) bone mineral density (BMD) response to daily treatment with teriparatide, although the impact was limited.

Background Venous thromboembolism (VTE) [i.e., pulmonary embolism (PE) and deep vein thrombosis (DVT)] is a common complication during and after a hospital admission. Further, VTE is a leading cause of major complications and death after major orthopedic surgery. To avoid the development of VTE after orthopedic surgery, it is essential to reduce the onset of deep vein thrombosis (DVT) and to diagnose DVT early. It leads to early diagnosis to find a risk factor of DVT from medical history of the patient. Total knee arthroplasty (TKA) reliably relieves pain and improves function in patients with end-stage arthropathy of the knee such as osteoarthritis (OA) and rheumatoid arthritis (RA). The most common complication after knee arthroplasty is DVT. However, the risk for preoperative DVT in patients for knee joint orthopedic surgery remains unclear. Therefore, we investigated the patient9s background and medical history in patients admitted to hospital for primary TKA, and identified the risk factors for DVT development before TKA. Objectives The objectives are investigated the risk factors of DVT in patients admitted for primary TKA. Methods Patients. From 2003 to 2013, 303 patients admitted for primary TKA at Mie University Hospital were eligible for the present retrospective study. The patients9 sex, weight, body mass index (BMI, weight in kilograms divided by the square of the height in meters), and data from the medical history and medical condition were recorded. Diagnosis of DVT. B-mode ultrasonography with compression and color Doppler imaging were performed for bilateral common femoral veins, the superficial veins, the popliteal veins, and the calf veins. Statistical analysis. The patients9 preoperative characteristics were compared between the DVT-positive and DVT-negative patients using the Mann-Whitney U test and Fisher9s exact test. Multiple linear regression analysis was performed to identify independent risk factors for preoperative DVT. P values <0.05 were considered statistically significant. Results The preoperative diagnosis was OA in 261 patients (86.1%) and RA in 42 patients. The most frequent preoperative medical history or medical condition was hypertension (52.1%). The second most frequent preoperative medical history or medical condition was major surgery (47.5%). Preoperative DVT was diagnosed in 48 of 303 (15.8%) patients overall. Significantly elevated risks of DVT were found in patients who had RA (p<0.05) using Fisher9s exact test. Multiple linear regression analysis was performed to test the association of DVT with putative risk factors. The analysis showed that admission for RA (p<0.05) were significant independent risk factors for preoperative DVT. Conclusions A high prevalence (15.8%) of preoperative asymptomatic DVT was found in patients admitted for primary TKA. In this study, RA was risk factors for preoperative DVT among those admitted to the hospital for primary TKA. Disclosure of Interest None declared

Background Factors of chronic pain due to hemiplegia or prolonged immobility are varied, there is osteoporosis (a rarefaction due to bone atrophy) as the cause. Osteoporotic patients with no evidence of fractures sometimes experience vague lower back pain. However, there have been few reports regarding the correlation between osteoporosis and pain-related behavior. Our previous studies have indicated that hindlimb-unloading induced bone loss and mechanical hyperalgesia in hindlimb of mice. We investigated the effects of teriparatide (PTH) on bone mass and pain-related behaviors in osteoporosis model mice with hindlimb unloading. Objectives The objective of the current study was to investigate the effect of PTH on bone mass and pain-related behaviors in hindlimb-unloaded mice model of disuse osteoporosis. Methods Male ddY mice (8 weeks old) were tail-suspended for 2 weeks and assigned to 3 groups; hindlimb-loaded mice treated with vehicle (control), hindlimb-unloaded mice treated with vehicle (HU), hindlimb-unloaded mice treated with PTH (HU-PTH) (n=8/group). Starting immediately after tail-suspension, vehicle or 40μg/kg PTH was injected subcutaneously twice a week for 2 weeks. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by micro-computed tomography (μCT) 2 weeks after tail-suspension. Mechanical sensitivity was also tested using von Frey filaments 2 week after the tail suspension. The withdrawal threshold, the 50% withdrawal threshold and the frequency of the withdrawal response to the application of von Frey filaments to the plantar surface of the hind paws was examined. Measurement of pain-related behavior with von Frey filaments was interpreted as indicative of mechanical allodynia. Results μCT analysis of the distal femoral metaphysis and the proximal tibial metaphysis showed that significantly decreased bone volume/tissue volume (BV/TV) and trabecular thickness (Tb.Th) in HU compared with HL was significantly increased by PTH treatment. (Fig.1) Similarly, decreased trabecular number (Tb.N) in HU compared with HL was increased, and increased trabecular separation (Tb.Sp) in HU compared with HL was decreased by PTH treatment, but not significant. The paw withdrawal threshold and the 50% paw withdrawal threshold were significantly lower in the HU than in the control, whereas it was significantly higher in the HU-PTH than in the HU group. (Fig.2) The paw withdrawal frequency stimulated by von Frey filaments with strength of 0.4–2.0 g was significantly higher in the HU than in the control. Whereas it was significantly lower in the HU-PTH than in the HU. Conclusions In this study, treatment of PTH prevented bone loss and mechanical hyperalgesia in disuse osteoporotic animal models by hindlimb-unloading. The results suggest that low bone volume itself is one of the causes of osteoporotic pain. Disclosure of Interest None declared

BackgroundOsteoporosis may cause not only fractures but also chronic back pain in elderly women. Bente reported that postmenopausal women with severe osteoporosis who were prescribed teriparatide (TPTD) in standard clinical practice had a reduction in back pain. However, there have been no reports regarding the effect of TPTD on pain in animal models of osteoporosis.ObjectivesThe objective of the current study was to investigate the effect of TPTD on pain-related behavior in ovariectomized (OVX) mice.MethodsFemale ddY mice (8 weeks old) were ovariectomized and assigned to 3groups; SHAM-operated mice treated with vehicle (SHAM), OVX mice treated with vehicle (OVX), OVX mice treated with TPTD (TPTD). Starting immediately after surgery, vehicle or 40μg/kg TPTD was injected subcutaneously 5 times a week for 4 weeks. The proximal tibial metaphysis were analyzed three-dimensionally by μCT 4 weeks after surgery (each group; 8 mice). Mechanical sensitivity was tested using von Frey filaments 4 weeks after surgery. To evaluate the withdrawal threshold, each von Frey filaments was applied once, starting with 0.008g and increasing until a withdrawal response was reached, which was considered a positive response. The lowest force producing a response was considered the withdrawal threshold. To evaluate the 50% withdrawal threshold, seven von Frey filaments were applied to the middle of the plantar surface. Testing was initiated with the 0.6g filament. In the absence of a clear paw withdrawal response, increasingly stronger filaments were presented consecutively, until one of them was found to elicit such a response. If the 0.6 g filament elicited a response, filaments with decreasing strength were presented until determination of the first one which failed to cause paw withdrawal. Data was collected using the up-down method. To identify osteoclasts in hindlimb bone, we used the tartrate-resistant acid phosphatase (TRAP) method. TRAP-positive multinucleated cells were scored as osteoclasts. Measurements were made within an area the proximal tibial metaphysis starting immediately below the growth plate. Histomorphometry was conducted to quantify the number of osteoclasts.ResultsμCT analysis of the proximal tibial metaphysis showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the OVX group than in the SHAM group, whereas trabecular separation (Tb.Sp) was significantly greater in the OVX group than in the SHAM group. In the TPTD group, BV/TV and Tb.N were significantly greater than in the OVX group, whereas Tb.Sp was significantly less than in the OVX group. The withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and it was significantly higher in the TPTD group than in the OVX group. Similarly, the 50% withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and it was significantly higher in the TPTD group than in the OVX group. The number of osteoclasts was significantly higher in the OVX group than in the SHAM group, whereas it was higher in the TPTD group than in the OVX group, but there were no significantly changes.ConclusionsTPTD prevented ovariectomy-induced bone loss. In addition, mechanical hyperalgesia in hindlimbs significantly improved in OVX group compared with TPTD group. The results suggest that TPTD prevented postmenopausal osteoporotic pain.Disclosure of InterestNone declared

The percent and absolute lumbar spine and femoral neck bone mineral densities and procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide level increases noted after teriparatide 20 μg/day treatment for 24 months were similar in the older (age ≥ 80 years) and younger (age < 80 years) subgroups.

Background Osteoporotic patients with no evidence of fractures sometimes experience vague lower back pain. A previous report has indicated that sensory innervation of ovariectomized rat vertebrae showed increased expression of the CGRP, a neuropeptide marker of pain, and the TRPV1, an acid-sensitive ion channel, in dorsal root ganglion (DRG) neurons1. However, there have been few reports regarding the correlation between osteoporosis, pain-related behavior and immunohistochemical analysis. Objectives The objective of the current study was to investigate pain-related behavior and to elucidate the mechanism of osteoporotic pain by immunohistochemical analysis of the DRG in hindlimb-unloaded (HU) mice model of disuse osteoporosis2. And we investigated the effect of alendronate (ALN) in HU mice. Methods Male ddY mice (8 weeks old) were tail-suspended for 2 week and assigned to 3 groups; hindlimb-loaded mice treated with vehicle (control), HU mice treated with vehicle (HUV), HU mice treated with ALN (HUA)(n=8/group). Starting immediately after tail-suspension, vehicle or 40μg/kg ALN was injected subcutaneously twice a week for 2 weeks. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by μCT 2 weeks after tail-suspension. Mechanical sensitivity was also tested using von Frey filaments 2 week after the tail suspension. The withdrawal threshold, the 50% withdrawal threshold and the frequency of the withdrawal response to the application of von Frey filaments to the plantar surface of the hind paws was examined. Immunohistochemical analysis of the CGRP expression and the TRPV1 expression was completed for the L4 and L5 DRG neurons. Results μCT analysis of the distal femoral metaphysis (Fig. 1a) and the proximal tibial metaphysis showed that significantly decreased bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) in HUV compared with control was significantly increased by ALN treatment. Significantly increased trabecular separation (Tb.Sp) in HUV compared with control was significantly decreased by ALN treatment. The paw withdrawal threshold and the 50% paw withdrawal threshold were significantly lower in the HUV than in the control, whereas it was significantly higher in the HUA than in the HUV group (Fig. 1b). The paw withdrawal frequency stimulated by von Frey filaments with strength of 0.4–2.0 g was significantly higher in the HUV than in the control. Whereas it was significantly lower in the HUA than in the HUV. The immunohistochemical analysis showed that the ratio of CGRP-immunoreactive (ir) and TRPV1-ir DRG neurons (L4 and L5) in the HUV was significantly higher than in the control, whereas it was significantly lower in the HUA than in the HUV. There was no significant difference between the HUA and the control in μCT analysis, hyperalgesia of hindlimbs and immunohistochemical analysis. Conclusions In this study, treatment of ALN prevented bone loss, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expression in DRG neurons of disuse osteoporotic animals models by hindlimb-unloading. The results suggest that bone resorption is one of the causes of osteoporotic pain. References Orita S et al. Spine. 2010. Barou O et al. Invest Radiol. 2002. Disclosure of Interest None declared

The percent and absolute lumbar spine and femoral neck bone mineral densities and absolute procollagen type I N-terminal propeptide (PINP) increases following a 20-μg/day teriparatide treatment for 12 months were similar in men and women regardless of sex differences.

Purpose: Advances in small arthroscopy have enabled a minimally invasive surgery for thumb carpometacarpal joints. However, surgery is often difficult using standard CM-radial (CM-R) and CM-ulnar portals ( CM-U). Here, we describe the clinical applications and complications associated with using thenar portal (TP) and standard portals.Methods: Arthroscopic surgeries of thumb carpometacarpal joint were performed in 21 patients including 15 patients with osteoarthritis and six Bennett's fracture-dislocations. Complications and the frequency of use associated with each portal were evaluated.Results: Complications associated with the CM-R portal comprised paresthesia due to damage of the radial nerve branches in two patients. No nerves were damaged but the operation scar became tender at the TP in three patients. The CM-R was used at a lower frequency when the TP was utilized.Conclusion: The clinical use of TP may decrease the risk of radial sensory nerve damage through decreasing frequency of use of the CM-R that is located near the nerve. (C) 2015 Elsevier Masson SAS. All rights reserved.