Background: Although varus-tilted distal tibial deformity is an established risk factor for chronic lateral ankle instability (CLAI), no studies have reported whether this deformity influences ankle instability after arthroscopic lateral ankle ligament repair (ALLR) for CLAI. Methods: A total of 57 ankles from 57 patients who underwent ALLR for CLAI were retrospectively analyzed. Tibial articular surface (TAS) angles were measured on preoperative plain radiograph. After 12 months of follow-up, recurrent ankle instability and talar tilt angles on stress radiograph were evaluated as outcomes. Relationships between the TAS angle and these outcomes were assessed. Results: Recurrent ankle instability was observed in 10 ankles. The TAS angles of patients with recurrent instability were significantly lower (85.2 degrees vs 87.9 degrees). The receiver operating characteristic curve analysis revealed that the cutoff value of TAS angle for recurrent instability was 86.2 degrees. Based on this cutoff value, our patients were divided into 2 groups: low-TAS and high-TAS group. Univariate and multivariate analysis revealed that low TAS was an independent risk factor for recurrent ankle instability and greater postoperative talar tilt angles. Conclusion: Varus-tilted distal tibial plafond appears to be a risk factor for recurrent ankle instability after ALLR.

Research on cartilage regeneration has developed novel sources for human chondrocytes and new regenerative therapies, but appropriate animal models for translational research are needed. Although rabbit models are frequently used in such studies, the availability of immunocompromised rabbits is limited. Here, we investigated the usefulness of an immunosuppressed rabbit model to evaluate directly the efficacy of human chondrocyte sheets through xenogeneic transplantation. Human chondrocyte sheets were transplanted into knee osteochondral defects in Japanese white rabbits administered with immunosuppressant tacrolimus at a dosage of 0.8 or 1.6 mg/kg/day for 4 weeks. Histological evaluation at 4 weeks after transplantation in rabbits administered 1.6 mg/kg/day showed successful engraftment of human chondrocytes and cartilage regeneration involving a mixture of hyaline cartilage and fibrocartilage. No human chondrocytes were detected in rabbits administered 0.8 mg/kg/day, although regeneration of hyaline cartilage was confirmed. Histological evaluation at 12 weeks after transplantation (i.e., 8 weeks after termination of immunosuppression) showed strong immune rejection of human chondrocytes, which indicated that, even after engraftment, articular cartilage is not particularly immune privileged in xenogeneic transplantation. Our results suggest that Japanese white rabbits administered tacrolimus at 1.6 mg/kg/day and evaluated at 4 weeks may be useful as a preclinical model for the direct evaluation of human cell‐based therapies.

Purpose The relationship between ligament remnant quality and postoperative outcomes after arthroscopic lateral ankle ligament repair for chronic lateral ankle instability is controversial. This study aimed to determine whether the signal intensity of the anterior taloibular ligament on preoperative magnetic resonance imaging and ligament remnant quality identiied on arthroscopy are associated with recurrent ankle instability after arthroscopic lateral ankle ligament repair. Methods A total of 68 ankles from 67 patients with chronic lateral ankle instability who underwent arthroscopic lateral ankle ligament repair were retrospectively studied. The signal intensity of the anterior taloibular ligament was evaluated using T2-weighted magnetic resonance imaging. Arthroscopy was used to evaluate the thickness and mechanical resistance of the anterior taloibular ligament by hook palpation and to classify ankles into two groups: the present anterior taloibular ligament group with adequate mechanical resistance and the absent anterior taloibular ligament group with no mechanical resistance. The outcomes included recurrent ankle instability (respraining of the operated ankle after surgery) and Self-Administered Foot Evaluation Questionnaire scores. Results Thirteen ankles were diagnosed with recurrent ankle instability. Patients with a high anterior taloibular ligament T2 signal intensity experienced more recurrent ankle instability than those with a low intensity. As determined via arthroscopy, the absent anterior taloibular ligament group had a higher rate of recurrent ankle instability than the present anterior taloibular ligament group. There were no signiicant diferences in Self-Administered Foot Evaluation Questionnaire scores between patients with high and low anterior taloibular ligament T2 signal intensity, as well as between absent and present anterior taloibular ligament groups based on arthroscopy. Conclusion Poor quality of the anterior taloibular ligament remnant could result in recurrent ankle instability after arthroscopic lateral ankle ligament repair. Therefore, when treating chronic lateral ankle instability, surgeons should consider ligament quality. Level of Evidence IV.

Leptin is a key regulator of energy intake and expenditure. This peptide hormone is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1 adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin promoter are highly methylated in 3T3-L1cells. 5-azacytidine, an inhibitor of DNA methyltransferase, markedly increased leptin expression as pre-adipocytes matured into adipocytes. Remarkably, leptin expression was stimulated by insulin in adipocytes derived from precursor cells exposed to 5-azacytidine, but suppressed by thiazolidinedione and dexamethasone. In contrast, adipocytes derived from untreated precursor cells were unresponsive to both 5-azacytidine and hormonal stimuli, although lipid accumulation was sufficient to boost leptin expression in the absence of demethylation. Taken together, the results suggest that leptin expression in 3T3-L1 cells requires DNA demethylation prior to adipogenesis, transcriptional activation during adipogenesis, and lipid accumulation after adipogenesis.

Although cell transplantation has attracted much attention in regenerative medicine, animal models continue to be used in translational research to evaluate safety and efficacy because cell sources and transplantation modalities are so diverse. In the present study, we investigated the regenerative effects of human chondrocyte sheets on articular cartilage in a xenogeneic transplantation model using immune‐deficient rats. Osteochondral defects were created in the knee joints of immune‐deficient rats that were treated as Group A, untreated (without transplantation); Group B, transplantation of a layered chondrocyte sheet containing 5.0 × 105 cells (layered chondrocyte sheet transplantation); Group C, transplantation of a synoviocyte sheet containing 5.0 × 105 cells (synoviocyte sheet transplantation); or Group D, transplantation of both a synoviocyte sheet plus a layered chondrocyte sheet, each containing 5.0 × 105 cells (synoviocyte sheet plus layered chondrocyte sheet transplantation). Histological evaluation demonstrated that Group B showed cartilage regeneration with hyaline cartilage and fibrocartilage. In Groups C and D, the defect was filled with fibrous tissue but no hyaline cartilage. Transplanted cells were detected at 4 and 12 weeks after transplantation, but the number of cells had decreased at 12 weeks. Our results indicate that layered chondrocyte sheet transplantation contributes to articular cartilage regeneration; this model proved useful for evaluating these regenerative effects.

Summary Romosozumab is an effective treatment for spine osteoporosis because it reduces the incidence of new fractures and significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications. Introduction Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody, which increases bone formation and suppresses bone resorption. The aim of our study was to elucidate the clinical effects, safety, and predictors of the effects of one-year romosozumab treatment. Methods This study was an observational study designed as a pre–post study in 262 patients. Romosozumab (210 mg) was administered subcutaneously once every 4 weeks during 12 months. We focused on incidence of new fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. Results There were five cases of new fractures during one-year romosozumab treatment. There were no fatal adverse events. Percent changes from baseline in the spine and total hip BMD after 12 months of romosozumab treatment were 10.67% and 2.04%, respectively. Romosozumab had better effects in cases of severe osteoporosis with low spine BMD, high TRACP-5b, and high iP1NP at the start of romosozumab treatment. The percent change in the spine BMD at 12 months was significantly lower in the group transitioning from bisphosphonates than in the group not previously treated with other anti-osteoporosis medications. Conclusion Romosozumab is an effective treatment for spine osteoporosis because it significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications.

Background: Hindfoot varus deformity is a known risk factor for chronic lateral ankle instability (CLAI). The impact of this deformity on clinical results following arthroscopic lateral ankle ligament repair (ALLR) for CLAI has not been studied. Methods: Sixty-three ankles from 62 patients who received ALLR for CLAI were retrospectively examined. Preoperative plain radiographs were used to measure tibial articular surface (TAS) angles, and long axial hindfoot alignment radiographs were used to measure tibiocalcaneal angles (TCAs) pre- and postoperatively. Results included ratings on the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) and recurrent ankle instability (respraining of the operated ankle following surgery). Results: Recurrent ankle instability, defined as incidence of any new ankle sprain after surgery reported in the follow-up period, occurred in 13 ankles. The TAS angles of these patients were significantly low, and their preoperative TCA was significantly high. Multivariate analysis showed that preoperative TCA was an independent risk factor for recurrent ankle instability. The threshold values for preoperative TCA for recurrent instability were determined via the receiver operating characteristic curve analysis to be 3.4 degrees. Patients were assigned to a low- or high-TCA group based on the reported average TCA (2.7 degrees) of healthy patients. In the high-TCA group, recurrent instability was significantly more frequent, and the scores on the pain subscale of the postoperative SAFE-Q were significantly lower. Conclusion: Hindfoot varus alignment was associated with pooreroutcomes after ALLR. Level of Evidence: Level III, retrospective comparative study.

The combination of first metatarsophalangeal joint arthrodesis and resection arthroplasty of all lesser metatarsal heads has been historically considered the golden standard treatment for rheumatoid forefoot deformities. However, as recent improved management of rheumatoid arthritis have reduced progression of joint destruction, the surgical treatments for rheumatoid forefoot deformities have gradually changed from joint-sacrificing surgery, such as arthrodesis and resection arthroplasty, to joint-preserving surgery. The aim of this literature review was to provide current evidence for joint-preserving surgery for rheumatoid forefoot deformities. We focused on the indications, specific outcomes, and postsurgical complications of joint-preserving surgery in this review.