Effects of metformin on knee joint capsule fibrosis in a diabetic mouse model.

Aims: The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Methods: Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro. Results: The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells. Conclusion: Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis.

Pain modulation by oxytocin.

Oxytocin (OXT) was discovered in 1906 as a substance that promotes the pregnancy and childbirth. It affects uterine contraction and lactation. Furthermore, as one of its physiological properties, it exerts analgesic effects. The living body has an ascending pathway that transmits pain stimuli from the periphery to the center and a descending pathway that regulates the dorsal horn neurons from the upper center downward. OXT is involved in the pain-inhibitory descending pathway and generally assumed to exert analgesic effects. In this article, we describe the pain-suppressive effects of OXT, among its many physiological effects.

Analyzing attempt and success factors for amputated digit replantation in Japan using the diagnosis procedure combination database.

The number of amputated finger replantation has declined in the USA and Germany in recent years; however, there have been no reports on recent trends in Japan. We examined the current practices, attempts, and success factors of digit replantation in Japan. We hypothesized that the rates of digit replantation and success rates were consistently standardized in Japan. The diagnosis procedure combination database was used to analyze 14004 cases from April 2014 to March 2020, excluding multiple-digit amputations, thus focusing on 13484 patients. We evaluated replantation success rates and identified factors influencing replantation decisions using multiple logistic regression analysis. The key findings included a higher frequency of replantation in thumb cases and surgeries during overtime hours, on Sundays, and in educational institutions. Success rates were notably higher for thumb replantations and patients under 20 years of age. Patients over 65 years of age treated with urokinase showed higher failure rates, unrelated to regional or hospital case volumes. The number of amputated digit replantation surgeries in Japan was high during overtime hours, on Sundays, and in educational institutions. Region, hospital type, and hospital case volume were not associated with a low success rate across Japan.

Clinical Outcomes and Return-to-Sport Rates following Fragment Fixation Using Hydroxyapatite/Poly-L-Lactate Acid Threaded Pins for Knee Osteochondritis Dissecans: A Case Series.

Osteochondritis dissecans (OCD) of the knee is an uncommon injury in young active patients. There is currently a lack of knowledge regarding clinical outcomes and return-to-sport rates after fragment fixation surgery using hydroxy appetite poly-L-lactic acid (HA/PLLA) threaded pins for knee OCD among athletes. Our purpose was to investigate the clinical outcomes and return-to-sport rates following osteochondral fragment fixation using HA/PLLA pins for the treatment of knee OCD lesions among athletes. A total of 45 patients were retrospectively reviewed. In total, 31 patients were excluded, and 14 patients were included. Pre- and postoperative patient-reported outcome scores (PROSs), including the International Knee Documentation Committee (IKDC) score and Knee Injury and Osteoarthritis Outcome Scale (KOOS), were compared. In addition, patients were categorized into four groups according to postoperative sports status: higher, same, lower than preinjury, or unable to return to sports. The mean age was 14.4 years (SD 1.67). All patients were male. All PROSs significantly improved at 6, 12, and 24 months postsurgery compared to presurgery. 50% of the patients returned to sports at the same or higher level after surgery. Fragment fixation using HA/PLLA pins leads to favorable clinical outcome scores and high return-to-sport rates in the treatment of athletes with knee OCD.

DAIR in treating chronic PJI after total knee arthroplasty using continuous local antibiotic perfusion therapy: a case series study.

BACKGROUND: Antimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for chronic PJI after total knee arthroplasty performed at our hospital. SUBJECTS AND METHODS: Six patients (male; one case, female; five cases, mean age 79.5 years (70-94)) underwent CLAP for chronic PJI after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17-219), with a mean follow-up of 24.3 months (12-36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment, and CLAP with gentamicin were performed using NPWT. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events. RESULT: Two of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients could preserve their components. The organisms responsible for the flare-ups were MSSA in three cases: ESBL-producing E. coli, mixed MSSA and streptococcal infection, Klebsiella pneumonia in one case each, and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5-16); iSAP, mean: 19.3 days (15-28); GM dose, mean: 162.5 mg/day (80-240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection. DAIR with CLAP for chronic post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.

Nitric oxide synthase contributes to the maintenance of LTP in the oxytocin-mRFP1 neuron of the rat hypothalamus.

Oxytocin (OXT) is a neuropeptide hormone that plays a critical role in nociception. Long-term potentiation (LTP) is a major form of synaptic plasticity in the central nervous system. Recently, LTP has been reported in the hypothalamus; however, data on LTP in hypothalamic OXT-ergic neurons are unclear. Furthermore, the signaling pathways for hypothalamic OXT-ergic neuronal LTP and its physiological significance remain unknown. Herein, we aimed to investigate the induction of hypothalamic OXT-ergic neuronal LTP and its synaptic mechanism using OXT-monomeric red fluorescent protein 1 transgenic rats to visualize and record from OXT-ergic neurons. The hypothalamic paraventricular nucleus (PVN) OXT-ergic neuronal LTP induced by the pairing protocol was dependent on N-methyl-D-aspartate receptor (NMDAR). Furthermore, nitric oxide synthase (NOS) is required to maintain the LTP regardless of the NMDARs. In addition, hypothalamic OXT-ergic neuronal LTP was not induced in the adjuvant arthritis rat model but increased excitatory postsynaptic currents were detected. LTP in hypothalamic OXT-ergic neurons in the PVN in the presence of NOS may be involved in neuronal changes during OXT synthesis in chronic inflammation.

Chemogenetic Activation of Oxytocin Neurons Improves Pain in a Reserpine-induced Fibromyalgia Rat Model.

Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. In FM model, OXT-monomeric red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer tryptophan hydroxylase (TPH)- and tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced serotonin and norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.

Validity and application of Doiguchi's pelvic tilt measurement method.

BACKGROUND: The validity of Doiguchi's pelvic tilt measurement method has not been proven. The objective in our study was to validate the method. METHODS: Our investigation included 73 total hip arthroplasties (THAs) performed using our cup placement procedure from July 2020 to November 2021. Pelvic tilt formed by the pubic symphysis and sacral promontory (PTPS) in supine and lateral positions was calculated by two methods (the Doiguchi method and the digital reconstructed radiograph (DRR) method using a 3D computer templating system) based on the transverse and longitudinal diameters of the pelvic ring measured immediately before THA. RESULTS: There was a strong/moderate correlation in the values of PTPS between the Doiguchi and DRR methods. However, the value of PTPS calculated by the Doiguchi method was significantly lower than that calculated by DRR, and there was a partially direct match. On the other hand, there was no significant difference in the value of PT change from supine to lateral position between the Doiguchi and DRR methods. The PT changes based on both methods were strongly correlated, and the PT change calculated by the Doiguchi method was almost identical to that calculated by the DRR method. CONCLUSIONS: Doiguchi's pelvic tilt measurement method was validated for the first time. These results demonstrated that the ratio of the transverse and longitudinal diameters of the pelvic ring was an important factor defining the change in pelvic tilt. The slope in the linear function of the Doiguchi method was found to be almost the correct value, although the intercept of the linear function exhibited individual differences.

Delayed cortical bone healing due to impaired nuclear Nrf2 translocation in COPD mice.

The effect of the pathogenesis of chronic obstructive pulmonary disease (COPD) on bone fracture healing is unknown. Oxidative stress has been implicated in the systemic complications of COPD, and decreased activity of Nrf2 signaling, a central component of the in vivo antioxidant mechanism, has been reported. We investigated the process of cortical bone repair in a mouse model of elastase-induced emphysema by creating a drill hole and focusing on Nrf2 and found that the amount of new bone in the drill hole was reduced and bone formation capacity was decreased in the model mice. Furthermore, nuclear Nrf2 expression in osteoblasts was reduced in model mice. Sulforaphane, an Nrf2 activator, improved delayed cortical bone healing in model mice. This study indicates that bone healing is delayed in COPD mice and that impaired nuclear translocation of Nrf2 is involved in delayed cortical bone healing, suggesting that Nrf2 may be a novel target for bone fracture treatment in COPD patients.

In Vivo Postoperative Motion of Fixed and Mobile Medial Pivot Knees Under Weight-Bearing Conditions after Cruciate-Sacrificing Total Knee Arthroplasty.

BACKGROUND: In vivo three-dimensional (3D) motion under weight-bearing conditions was analyzed postoperatively in medial pivot cruciate-substituting (CS) knee systems with fixed and mobile inserts. METHODS: Tibiofemoral knee kinematics during squatting were captured with X-ray fluoroscopy for 4 patients in each cohort. The 3D motion of implants was analyzed with KneeMotion motion analysis software (LEXI Corporation; Tokyo, Japan). In addition, anterior-posterior (AP) movement of the distal-most points and the angle of axial rotation of the femoral component on the tibial component were assessed in both cohorts. RESULTS: Mean AP movement of the femoral component on the tibial component was 3.8±0.5 mm on the medial side and 9.5±0.5 mm on the lateral side in the cohort with fixed prostheses and 5.9±2.1 mm on the medial side and 10.0±2.5 mm on the lateral side in the cohort with mobile prostheses. The mean angle of axial rotation of the femoral component on the tibial component was 14.4±1.1 degrees and 8.2±2.7 degrees of external rotation for fixed knees and mobile knees, respectively. CONCLUSIONS: Postoperative motion analysis confirmed that fixed and mobile CS implants, which have a similar design, guided medial pivot motion under weight-bearing conditions. However, motion differed between these implant types after mid-flexion: bicondylar rollback after medial pivot motion was noted in the mobile cohort.

A case of bone metastasis of hepatocellular carcinoma: Mallory hyaline bodies can lead to the correct cytological diagnosis.

Hepatocellular carcinoma (HCC) accounts for most primary tumors of the liver. Although bone metastasis does not occur in a high percentage of patients, bone metastasis is often found first, which leads to the diagnosis of HCC. In this report, we describe a case of bone metastasis from HCC in which bone lesions were detected incidentally, and in which a cytological diagnosis was difficult to make. The patient was a 78-year-old man with a history of renal dysfunction after orthopedic surgery. He underwent a thorough examination after a bone tumor was incidentally found on abdominal CT. Plasmacytoma was suspected. Fine needle aspiration cytology revealed irregular clusters of medium-to-large atypical epithelioid polygonal cells with relatively abundant eosinophilic, somewhat granular cytoplasm, and indistinct cell borders, which led to a diagnosis of malignancy. Histologically and immunohistochemically, the tumor was diagnosed as bone metastasis of HCC. Re-examination of the cytological specimen revealed characteristic Mallory hyaline bodies (MHBs). Immunohistochemistry using a cell transfer method revealed that they were positive for low molecular weight cytokeratin, Cam5.2, in a densely granular fashion. In this case, the cytological diagnosis of HCC was difficult to make due to the unclear cytoplasmic borders and absence of bile pigment. However, the identification of MHBs can potentially guide me to the correct cytological diagnosis.

Trabecular Bone Volume Is Reduced, With Deteriorated Microstructure, With Aging in a Rat Model of Duchenne Muscular Dystrophy.

We aimed to clarify the effect of aging on trabecular bone volume and trabecular bone microstructure in a rat model of Duchenne muscular dystrophy (DMD). Six rats each of wild type (WT) and DMD model at 15 weeks of age, and 4 rats each at 30 weeks of age, were analyzed by dual energy X-ray absorptiometry and by micro-CT for analysis of trabecular and cortical bone of the femur. Bone mineral density was significantly lower in the DMD group than in the WT group at both 15 and 30 weeks of age. Micro-CT showed that trabecular bone volume and number were not significantly different between the two groups at 15 weeks, but at 30 weeks both were significantly lower in the DMD group than in the WT group. Connectivity density and structure model index were not significantly different between the two groups at 15 weeks, but at 30 weeks they differed significantly. No significant differences between the WT and DMD groups in cortical thickness and cortical area were evident at both 15 and 30 weeks. In conclusion, trabecular bone volume is significantly reduced, with deteriorated microstructure, with aging in a rat model of DMD.

Assessment of influences of posterior rotation of the tibial condyles on the Insall-Salvati ratio.

The positional relationship between patellar and femoral articular surfaces may vary according to the degree of posterior rotation of the tibial condyle, which may influence the patellar configuration. We hypothesized that the configuration of the patella has a rhomboid transformation similar to that of the tibial condyle. This cohort study included 313 patients with knee pain who underwent lateral-view knee digital radiography. The length of the long axis, short axis of the patella, and patellar tendon length of the patellofemoral joint were measured. The patella axis ratio (length of long/short axis) as patellar configuration and Insall-Salvati ratio were calculated. Correlations between the configuration of the tibial condyle and the three length parameters and the Insall-Salvati ratio were assessed. Posterior rotation and the rhomboid transformation of the tibial condyle were positively correlated with the length of the long axis of the patella and negatively correlated with the Insall-Salvati ratio. The more the tibial articular surface shifted posteriorly due to posterior rotation and rhomboid transformation of the tibial condyle, the longer the long axis of the patella was, and the smaller the Insall-Salvati ratio was. The long axis of the patella became longer due to rhomboid transformation, similar to the tibial condyle.

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats.

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model.

INTRODUCTION: Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models. MATERIALS AND METHODS: Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor. RESULTS: The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway. CONCLUSIONS: This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.

Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat.

Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS.

Accurate cup placement using a portable navigation system during total hip arthroplasty based on pelvic orientation in the lateral decubitus position.

BACKGROUND: We previously proposed an accurate cup placement procedure using a portable navigation system (PNS) for total hip arthroplasty (THA) in the lateral decubitus position; however, the accuracy of our proposed procedure has not been shown, the aim of this study was to demonstrate the accuracy. METHODS: We prospectively analyzed 79 hips treated with primary THA; 40 hips treated until June 2020 were included in the conventional procedure (CP) group, and 39 hips treated from July 2020 were included in the modified procedure (MP) group. In the MP, pelvic orientation is considered to be the set coordinate axes in addition to the CP using the PNS. The accuracy was based on the difference between the navigation record (NR) and postoperative computed tomography measurement. RESULTS: The radiographic inclination (RI) and anteversion (RA) accuracies were 1.55° and 2.14°, respectively, in the MP group and 3.03° and 6.20°, respectively, in the CP group (p < 0.001). The error was within 5° of the NR for both the RI and RA in 34 in the MP group (87.2%) and 14 in the CP group (35.0%) (p < 0.001). The error was within 5° of the target angle (RI 40°, RA 15°) for both the RI and RA in 29 hips in the MP group (74.7%) and 12 in the CP group (30.0%) (p < 0.001). CONCLUSIONS: Our procedure with the consideration of pelvic orientation achieved dramatically improved the accuracy of PNS and was suitable to facilitate accurate cup placement.

Biomechanical comparison of lag screw and non-spiral blade fixation of a novel femoral trochanteric nail in an osteoporotic bone model.

There is no consensus regarding the advantages of the lag screw type over the blade type for treating femoral trochanteric fractures. We aimed to investigate whether non-spiral blade (Conventional-Blade, Fid-Blade) nails provide better biomechanical fixation than lag screws in a severe osteoporotic bone model. Different severities of osteoporotic cancellous bone were modelled using polyurethane foam blocks of three densities (0.24, 0.16, and 0.08 g/cm3). Three torsional tests were performed using each component for each density of the polyurethane block, and the maximum torque was recorded; subsequently, the energy required to achieve 30° rotation was calculated. Using a push-in test, the maximum force was recorded, and the energy required to achieve 4-mm displacement was calculated. For 0.08-g/cm3 density, the peak torques to achieve 30° rotation, energy required to achieve 30° rotation, peak force to achieve 4-mm displacement, and energy required to achieve 4-mm displacement were significantly greater for Conventional-Blade and Fid-Blade than those for Lag Screw. The fixation stability of the blade-type Magnum nail component is better than that of the lag screw type under any test condition. The blade-type nail component may have better fixation stability than the lag screw type in a severe osteoporotic bone model.

Development of a novel knee contracture mouse model by immobilization using external fixation.

AIMS: Several studies have used animal models to examine knee joint contracture; however, few reports detail the construction process of a knee joint contracture model in a mouse. The use of mouse models is beneficial, as genetically modified mice can be used to investigate the pathogenesis of joint contracture. Compared to others, mouse models are associated with a lower cost to evaluate therapeutic effects. Here, we describe a novel knee contracture mouse model by immobilization using external fixation. METHODS: The knee joints of mice were immobilized by external fixation using a splint and tape. The passive extension range of motion (ROM), histological and immunohistochemical changes, and expression levels of fibrosis-related genes at 2 and 4 weeks were compared between the immobilized (Im group) and non-immobilized (Non-Im group) groups. RESULTS: The extension ROM at 4 weeks was significantly lower in the Im group than in the Non-Im group (p < 0.01). At 2 and 4 weeks, the thickness and area of the joint capsule were significantly greater in the Im group than in the Non-Im group (p < 0.01 in all cases). At 2 weeks, the mRNA expression levels of the fibrosis-related genes, except for the transforming growth factor-ß1, and the protein levels of cellular communication network factor 2 and vimentin in the joint capsule were significantly higher in the Im group (p < 0.01 in all cases). CONCLUSION: This mouse model may serve as a useful tool to investigate the etiology of joint contracture and establish new treatment methods.

Bone microstructure changes due to once-/twice-weekly teriparatide administration: A report of five cases using high-resolution peripheral quantitative computed tomography.

This study was conducted with the aim of presenting cases in which high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate changes in the bone microstructure due to once-weekly/twice-weekly administration of teriparatide (TPTD). Of osteoporosis patients who participated in a non-inferiority trial (TWICE study: once-weekly vs twice-weekly TPTD) with lumbar bone mineral density as the primary endpoint, five cases scanned by HR-pQCT before TPTD administration were analysed. Two cases were given once-weekly TPTD, three were given twice-weekly TPD, and HR-pQCT was repeated after 48 weeks. A sufficient anabolic effect of once-weekly/twice-weekly TPTD on the trabecular and cortical bone at the tibia was obtained. In addition, the average change in cortical porosity (Ct.Po) was only 0.3% in the tibia and 0.2% in the radius. These findings indicate that once-weekly and twice-weekly TPTD can be expected to improve the bone microstructure, and the increase in Ct.Po may be suppressed.