Impact of baseline PINP on the BMD increase with romosozumab, teriparatide, and denosumab in treatment-naïve primary osteoporosis: A retrospective cohort study.

Purpose: To investigate the impact of baseline total N-terminal propeptide of procollagen (PINP) levels on increases in bone mineral density (BMD) after treatment with romosozumab (ROMO), teriparatide (TPTD), and denosumab (DMAb) in patients with treatment naïve primary osteoporosis.

Methods: This multicenter, retrospective cohort study included 462 treatment-naïve patients (88.7 % female; mean age, 75.

Receptor activator of nuclear factor-kappa B ligand-derived microglia healing peptide 1-AcN inhibits osteoarthritis progression in mice.

Background: Osteoarthritis (OA) is a degenerative disease characterized by subchondral bone sclerosis, chronic inflammation, and cartilage degradation. Abnormal mechanical stress by meniscal deviation activates osteoclasts and induces the release of transforming growth factor-beta (TGF-β), which promotes mesenchymal stem cell (MSC)-mediated type H angiogenesis and osteogenesis, contributing to bone sclerosis and cartilage damage. Subsequently, macrophages recognize cartilage-derived damage-associated molecular patterns (DAMPs) via Toll-like receptor 4 (TLR4), polarizing into the pro-inflammatory M1 phenotype, thereby exacerbating synovitis and cartilage loss.

Differential Impact of Concomitant Methotrexate and Glucocorticoids Dosages on Biologics and JAK Inhibitors: The ANSWER Cohort Study.

Aim: This multicenter retrospective study evaluated the differential impact of concomitant methotrexate (MTX) and glucocorticoids (GCs) administration by dosage on the effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) in a real-world cohort of patients with rheumatoid arthritis, adjusting for clinical backgrounds variables.

Methods: The study included 3751 treatment courses (bDMARD- or JAKi-naïve cases, 48.9%; tumor necrosis factor inhibitors: 1668; tocilizumab [TCZ]: 865; abatacept [ABT]: 825; JAKi: 393).

Predicting rheumatoid arthritis progression from seronegative undifferentiated arthritis using machine learning: a deep learning model trained on the KURAMA cohort and externally validated with the ANSWER cohort.

Background: Undifferentiated arthritis (UA) often develops into rheumatoid arthritis (RA), but predicting disease progression from seronegative UA remains challenging because seronegative RA often does not meet the classification criteria. This study aims to build a machine learning (ML) model to predict the progression from seronegative UA to RA using clinical and laboratory parameters.

Methods: KURAMA cohort (training dataset) and ANSWER cohort (validation dataset) were utilized.

Sustained efficacy of second-line JAK inhibitors in patients with rheumatoid arthritis: insights from the ANSWER cohort.

Objectives: This multicentre, retrospective study aimed to evaluate differences in drug continuation rates and efficacy between first- and second-line use of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) after failure of the initial therapy in real-world RA settings.

Methods: Data from an observational multicentre registry of patients with RA in Japan were analysed, encompassing 5900 treatment courses (4046 bDMARD/JAKi-naïve cases and 1854 second-line cases). Gray's tests were used to compare the cumulative incidence function (CIF) for drug discontinuation, considering discontinuation due to remission as a competing risk.

Distinct impact of RF and ACPA titre on the effectiveness and persistency of biologics and JAK inhibitors: The ANSWER cohort study.

Objectives: We aimed to identify the impact of rheumatoid factor (RF) or anticyclic citrullinated peptide antibody (ACPA) titres on the retention of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) in patients with rheumatoid arthritis.

Methods: We retrospectively analysed 5312 courses of bDMARDs or JAKis from the ANSWER cohort. To calculate hazard ratios (HRs) for treatment discontinuation, we used multivariate Cox proportional hazards modelling, adjusted for potential confounders.

Mid-term outcomes of distal tibial oblique osteotomy for rheumatoid arthritis-associated ankle arthropathy: A comparison with osteoarthritis outcomes.

Background: Distal tibial oblique osteotomy (DTOO) has traditionally been contraindicated in 'patients with rheumatoid arthritis (RA)'. However, with advances in RA treatment, an increasing number of patients present with arthritis resembling osteoarthritis (OA), suggesting DTOO as a potential option. This study aimed to compare mid-term clinical and radiographic outcomes of DTOO between the patients with OA and RA.

RANKL-derived peptide MHP1-AcN attenuates ovariectomy-induced osteoporosis by targeting RANK and TNFR1 in mice.

Purpose: Estrogen deficiency following menopause increases receptor activator of nuclear factor-kappa B ligand (RANKL) expression in osteoblasts, thereby promoting osteoclast differentiation, and enhances T cell-derived tumor necrosis factor-alpha (TNFα) production, which induces sclerostin expression in osteocytes, thereby inhibiting bone formation. This study aimed to develop a novel uncoupling therapeutic agent for osteoporosis.

Methods: We developed microglial healing peptide 1 with N-terminal acetylation and C-terminal amidation (MHP1-AcN), a modified RANKL peptide with N-terminal acetylation and C-terminal amidation lacking the osteoclast activating CD loop.

Impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in patients with postmenopausal osteoporosis: a case-control study.

Unlabelled: This case-control study investigated the impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in postmenopausal osteoporosis. Romosozumab demonstrated the most significant improvements in bone mineral density, particularly in the lumbar spine and total hip, by reducing bone resorption and increasing bone formation markers.

Purpose: To investigate the impact of switching from bisphosphonates (BP) to denosumab (DMAb), teriparatide (TPTD), or romosozumab (ROMO) in postmenopausal osteoporosis.

New Surgical Approach and Rehabilitation After Cemented Total Ankle Arthroplasty.

Background: According to the conventional postoperative procedure after total ankle arthroplasty (TAA) for end-stage osteoarthritis (OA) and rheumatoid arthritis (RA), mobilization and weight-bearing are currently started after completion of wound healing. Recently, an early rehabilitation program after cemented TAA with a modified anterolateral approach has been attempted because this approach could provide stable wound healing. To investigate the possibility of expediting rehabilitation, this study evaluated the feasibility, safety, and universality of an early rehabilitation program after cemented TAA using a modified anterolateral approach, even when a surgeon was completely changed.

Impact of prior teriparatide treatment on the effectiveness of romosozumab in patients with postmenopausal osteoporosis: A case-control study.

Purpose: To evaluate the impact of prior teriparatide (TPTD) treatment on the effectiveness of romosozumab (ROMO) in postmenopausal osteoporosis.

Methods: In this retrospective, case-controlled, multicenter study, 323 postmenopausal patients were initiated ROMO. Of these, 275 were treatment-naïve, and 48 were switched from TPTD, with uninterrupted ROMO treatment for 12 months.

Utility of external fixation for traumatic periprosthetic fracture after total ankle arthroplasty in patients with rheumatoid arthritis: A report of two cases.

This report describes two cases of implant-stable traumatic periprosthetic fractures after total ankle arthroplasty in patients with rheumatoid arthritis. One case with a low body mass index (14 kg/m2) achieved complete bone union with the use of an external fixator, while the other case with a high body mass index (32.83 kg/m2) failed to achieve bone union with the external fixator; however, complete union was achieved utilising secondary internal plate fixation.

Seronegative rheumatoid arthritis found in an 85-year-old woman during preoperative investigations for knee replacement surgery for osteoarthritis.

This report describes the case of an 85-year-old woman who was found to have seronegative rheumatoid arthritis during preoperative investigations for knee replacement surgery for osteoarthritis. Follow-up for knee osteoarthritis was continued for many years without any symptoms involving other joints. Before total knee arthroplasty for osteoarthritis, preoperative investigations revealed a highly inflammatory state.

The pivotal role of the Hes1/Piezo1 pathway in the pathophysiology of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) lacks fully effective treatments. This study investigated the role of Piezo1, a mechanosensitive ion channel component 1, in GIOP. We found reduced Piezo1 expression in cortical bone osteocytes from patients with GIOP and a GIOP mouse model.

Modified scarf osteotomy has a possible capability to be indicated against very severe hallux valgus deformity.

Background: Generally, scarf osteotomy is recommended for moderate-severe hallux valgus (HV) deformity. Although severe HV deformity is defined to be more than 40 degree (°), this definition of angular setting includes broad range of HV angle (HVA). Actually, very severe HV deformity such as more than 60° of the HVA is often seen.

Mid-term outcomes of distal tibial oblique osteotomy in patients with rheumatoid arthritis: A report of three cases.

Although distal tibial oblique osteotomy (DTOO) has usually been indicated for noninflammatory diseases such as osteoarthritis, we encountered three patients with rheumatoid arthritis (RA) who underwent DTOO. We evaluated radiographic parameters and clinical scores, including self-reported scores for the foot and ankle [self-administered foot evaluation questionnaire (SAFE-Q)] and the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale. In all three cases, radiographic improvements were achieved along with improvements in SAFE-Q and JSSF scores after mid-term follow-up.

Arthroscopic treatment of septic arthritis of the ankle joint caused by streptococcus in patients with chronic inflammatory diseases: Two case reports.

This report describes the arthroscopic treatment of septic arthritis of the ankle joint in two patients with inflammatory diseases, including rheumatoid arthritis and nail psoriasis. We treated both the ankle joints with antibiotic administration and urgent arthroscopic synovectomy and irrigation, although the procedure was performed several days (4 and 6 days) after the time at which the infection would have occurred. Fortunately, no recurrence has been seen for >18 and 20 months, respectively, after surgery, without antibiotic administration.

Flatfoot Surgery for Flexible Progressive Collapsing Foot Deformity With Inflammatory Joint Diseases: A Report of 3 Cases.

Case: Three cases of inflammatory joint diseases (systemic lupus erythematosus and ongoing juvenile idiopathic arthritis) with painful flexible progressive collapsing foot deformity (PCFD) underwent flatfoot surgery. All cases maintained sufficient radiological correction and achieved good clinical condition at final follow-up.

Conclusion: Although the prospect for recurrence of the deformity is not clear, even in inflammatory joint diseases, flat foot surgery such as flexor digitorum longs transfer, spring ligament reconstruction, and lateral column lengthening could have a possibility to be indicated against PCFD, as long as disease activity could be well suppressed by drug therapy, subsequently subtalar and talonavicular joints could be preserved.

Clinical effects of teriparatide, abaloparatide, and romosozumab in postmenopausal osteoporosis.

In the management of osteoporosis, anti-resorptive agents serve as a primary therapeutic approach. However, in cases where individuals exhibit an increased susceptibility to fractures, such as those characterized by severe low bone mass or a history of vertebral or hip fractures that markedly diminish life expectancy, the immediate reduction of fracture risk through the administration of osteoanabolic agents could be beneficial. Teriparatide, available in daily, once-weekly, or twice-weekly dosages, along with abaloparatide and romosozumab, constitutes a trio of such agents.

Cyclic compressive loading induces a mature meniscal cell phenotype in mesenchymal stem cells with an atelocollagen-based scaffold.

Biomechanical stimulation is reportedly pivotal in meniscal regeneration, although its effect on mesenchymal stem cell (MSC) meniscal differentiation remains elusive. In this study, we investigated how cyclic compressive loading (CCL) could impact MSCs using three-dimensional cultures in atelocollagen-based meniscal substitute (ACMS). We extracted MSCs from the meniscus, synovium, and articular cartilage, cultured them in three-dimensional cultures, and exposed them to CCL for 7 days.

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study.

Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort).

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

Objectives: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi).

Methods: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice.

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes.