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 biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 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. RESULTS: Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.

Prediction of Occurrence of Cerebral Infarction After Successful Mechanical Thrombectomy for Ischemic Stroke in the Anterior Circulation by Arterial Spin Labeling.

PURPOSE: The overall goal of our study is to create modified Alberta Stroke Program Early Computed Tomography Score (ASPECTS) determined by the findings on arterial spin labeling imaging (ASL) to predict the prognosis of patients with acute ischemic stroke after successful mechanical thrombectomy (MT). Prior to that, we examined predictive factors including the value of cerebral blood flow (CBF) measured by ASL for occurrence of cerebral infarction at the region of interest (ROI) used in the ASPECTS after successful MT. METHODS: Of the 92 consecutive patients with acute ischemic stroke treated with MT at our institution between April 2013 and April 2021, a total of 26 patients who arrived within 8 h after stroke onset and underwent MT resulting in a thrombolysis in cerebral infarction score of 2B or 3 were analyzed. Magnetic resonance imaging, including diffusion-weighted imaging (DWI) and ASL, was performed on arrival and the day after MT. The asymmetry index (AI) of CBF by ASL (ASL-CBF) before MT was calculated for 11 regions of interest using the DWI-Alberta Stroke Program Early CT Score. RESULTS: Occurrence of infarction after successful MT for ischemic stroke in the anterior circulation can be expected when the formula 0.3211â€¯× history of atrial fibrillation +0.0096â€¯× the AI of ASL-CBF before MT (%) +0.0012â€¯× the time from onset to reperfusion (min) yields a value below 1.0 or when the AI of ASL-CBF before MT is below 61.5%. CONCLUSION: The AI of ASL-CBF before MT or a combination of a history of atrial fibrillation, the AI of ASL-CBF before MT, and the time from onset to reperfusion can be used to predict the occurrence of infarction in patients arriving within 8 h after stroke onset in which reperfusion with MT was successful.

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors-A 2023 Update.

With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease-like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.

Visual Evoked Potential Can Predict Deterioration of Visual Function After Direct Clipping of Paraclinoid Aneurysm With Anterior Clinoidectomy.

BACKGROUND: The role of visual evoked potential (VEP) in direct clipping of the paraclinoid internal carotid artery (ICA) aneurysm remains uncertain. OBJECTIVE: To examine whether intraoperative neuromonitoring with VEP can predict deterioration of visual function after direct clipping of the paraclinoid ICA aneurysm with anterior clinoidectomy. METHODS: Among consecutive 274 patients with unruptured cerebral aneurysm, we enrolled 25 patients with paraclinoid ICA aneurysm treated by direct clipping after anterior clinoidectomy with intraoperative neuromonitoring with VEP in this study. We evaluated the visual acuity loss (VAL) and visual field loss (VFL) before surgery, 1 month after surgery, and at the final follow-up. RESULTS: The VAL at 1 month after surgery (VAL1M) and VAL at the final follow-up (Final VAL) were significantly related to the reduction rate of VEP amplitude at the end of surgery (RedEnd%), more than 76.5%, and the maximal reduction rate of VEP amplitude during surgery (MaxRed%), more than 66.7% to 70%. The VFL at 1 month after surgery (VFL1M) and the VFL at the final follow-up (Final VFL) were significantly related to MaxRed% more than 60.7%. CONCLUSION: VAL1M, Final VAL, VFL1M, and Final VFL could be significantly predicted by the value of RedEnd% and MaxRed% in direct clipping of Al-Rodhan group Ia, Ib, and II paraclinoid ICA aneurysms with anterior clinoidectomy.

Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Difficult-to-treat rheumatoid arthritis: Current concept and unsolved problems.

Over the past several decades, the treatment of rheumatoid arthritis (RA) has advanced significantly, and clinical, structural, and functional remission are achievable therapeutic goals. However, a substantial number of patients show resistance to multiple drugs. In particular, patients whose disease activity cannot be controlled despite the use of two or more biological disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs (tsDMARDs) with different mechanisms of action (MOA) have recently been referred to as having difficult-to-treat RA (D2T RA). D2T RA is a heterogeneous and multifactorial disease state, and the major problems are uncontrolled disease activity and decreased quality of life, as well as the economic burden due to frequent healthcare utilization and multiple admissions. Since the concept of D2T RA is relatively new and publication regarding D2T RA is limited, the mechanism underlying DMARD inefficacy and which factors form a "difficult-to-treat" state in such patients are not yet fully understood. It is also possible that factors contributing to D2T RA may differ by patient, sex, country, and race. The present Mini Review introduces the current concept and unsolved problems of D2T RA, including the definition, prevalence, and factors contributing to D2T RA. We then discuss the management and therapeutic strategies for D2T RA. Finally, we explore a clinical approach to prevent patients from developing D2T RA.

Factors affecting global neurocognitive status and frontal executive functions in the early stage after surgical clipping of unruptured anterior circulation aneurysms with respect to keyhole clipping and conventional clipping.

PURPOSE: This study investigated the most significant factor for the preservation of the global neurocognitive status and frontal executive functions in the surgical clipping of unruptured anterior circulation aneurysms, specifically in keyhole and conventional clipping procedures. METHODS: The prospective study that was performed to examine the effects of aneurysm surgery on the patient's global neurocognitive status and frontal executive functions started on April 2016. After exclusion posterior circulation aneurysms, anterior communicating aneurysms treated by interhemispheric approach, giant aneurysms, and paraclinoid aneurysms, 23 patients who were enrolled before May 2017 were treated by conventional clipping, and 18 patients who were enrolled after June 2017 were treated by keyhole clipping. Two patients were excluded from each group due to missing data. Finally, 21 and 16 patients in each group were analyzed, respectively. Three-tesla magnetic resonance imaging was performed before and after surgery to detect the presence of perioperative cerebral infarctions and brain edema. The Mini-Mental State Examination, Frontal Assessment Battery, and Self-Rating Depression Scale scores were obtained before and 1 month after surgery. RESULTS: Logistic regression analyses indicated that anterior communicating and internal carotid artery aneurysms were the most significant factors for poor outcomes and that keyhole clipping for these two types of aneurysm was the most significant factor for the preservation of patient global neurocognitive status. Keyhole clipping was also the most significant factor for the preservation of frontal executive functions in patients. CONCLUSIONS: Keyhole clipping may be more favorable than conventional clipping for the preservation of the global neurocognitive status and frontal executive functions. Moreover, it may be the most effective factor for preservation of global neurocognitive status when it is indicated for anterior communicating or internal carotid artery aneurysms.

Prediction of Post-operative Long-Term Outcome of the Motor Function by Multimodal Intraoperative Neuromonitoring With Transcranial Motor-Evoked Potential and Spinal Cord-Evoked Potential After Microsurgical Resection for Spinal Cord Tumors.

Objective: To examine the effect of multimodal intraoperative neuromonitoring on the long-term outcome of motor function after microsurgical resection for spinal cord tumors. Materials and Methods: Consecutive fourteen patients with spinal tumors who were surgically treated at the University of Fukui Hospital between 2009 and 2020 [M:F = 10:4, ages ranging from 22 to 83 years (mean ± SD = 58 ± 21 years)] were included in this study. There were eight intra-axial tumors and six extra-axial tumors. There were four patients with hypertension, two patients with diabetes mellitus, and four patients with hyperlipidemia. Three patients were under antithrombotic medication, two were under steroid medication, four were current smokers, and four were current drinkers. Manual muscle test (MMT) of the upper and lower extremities of the patients was examined before surgery, 2 weeks after surgery, and at the final follow-up. The mean follow-up period was 38 ± 37 months. McCormick scores were examined before surgery and at the final follow-up. Microsurgical resection of the tumor was underwent through the posterior approach under transcranial motor-evoked potential (TcMEP) monitoring. The MEP of 46 extremities was recorded during the surgery. Gross total resection was achieved in 13 of 14 surgeries. Spinal cord-evoked potential (Sp-SCEP) monitoring was performed in eight of 14 patients. Results: The length of peritumoral edema was significantly longer in patients with deterioration of McCormick scores than in patients with preservation of McCormick scores (p = 0.0274). Sp-SCEP could not predict the deterioration. The ratio of MEP at the beginning of the surgery to that at the end of the surgery was the only significant negative factor that predicts deterioration of motor function of the extremity at the final follow-up (p = 0.0374, odds ratio [OR] 1.02E-05, 95% CI 9.13E+01-7.15E+18). A receiver operating characteristic (ROC) analysis revealed that the cutoff value of the ratio of MEP to predict the deterioration at the final follow-up was 0.23 (specificity 100%, specificity 88%, positive predictive value 100%, and negative predictive value 88%) to predict deterioration at the final follow-up. Conclusions: Ratio MEP was the most significant negative factor to predict the deterioration of motor weakness at spinal tumor surgery. The setting of the cutoff value should be more strict as compared to the brain surgery and might be different depending on the institutions.

Functional Outcomes of Microsurgical Resection for Cavernous Malformations of the Brainstem.

Long-term functional outcomes of microsurgical resection for cavernous malformations of the brainstem (CMB) have been largely unknown. Favorable outcomes after CMB surgery might be related to the achievement of complete resection and mRS at 1 month after the surgery. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms tended to improve after surgery.We evaluated 25 consecutive patients with CMB surgically treated at our center between 2006 and 2021. The subjects included 11 men and 14 women, with ages ranging from 13 to 61 years (mean ± SD = 37 ± 12 years). Modified Rankin Scale (mRS) scores and neurological symptoms of the patients were evaluated before surgery, 1 month after surgery, and at the final follow-up at the outpatient clinic. The mean number of previous hemorrhages was 7 ± 1.0 and the mean lesion size was 21 ± 8 mm. The mRS scores on admission and at the final follow-up were 2.9 points and 1.7 points, respectively. The mRS scores at the final follow-up were significantly improved compared to those on admission. There was no statistical difference between the preoperative mRS and mRS at 1 month after the operation. Multivariable analysis indicated that mRS scores at 1 month after surgery were the most significant predictive factors for favorable outcomes. Complete resection was achieved in 24 of 33 operations. Incomplete resection was significantly related to the frequency of subsequent recurrent hemorrhage and high mRS scores at the final follow-up. Preoperative sensory, cerebellar, trigeminal nerve, and lower cranial nerve symptoms improved significantly after surgery.

Bexarotene-induced central hypothyroidism assessed by TRH stimulation test in cutaneous T-cell lymphoma patients.

Bexarotene-induced central hypothyroidism (CH), for which levothyroxine (LT4) replacement is recommended, has been shown to be caused by pituitary but not hypothalamic disorder experimentally, though the underlying mechanism in humans remains unclear. Here, the pathophysiology of bexarotene-induced CH was examined using a TRH stimulation test in cutaneous T-cell lymphoma (CTCL) patients. In this retrospective longitudinal observational study, serum TSH and free T4 (F-T4) levels were measured in 10 euthyroid patients with CTCL during 24 weeks of bexarotene treatment. TRH stimulation testing was performed following CH diagnosis, with LT4 replacement dosage adjusted to maintain F-T4 at the pre-treatment level. After one week of bexarotene administration, all 10 patients developed CH, based on combined findings of low or low-normal F-T4 with low or normal TSH levels. TSH peak response after a stimulation test at one week was reached at 30 minutes. However, that was <4 µIU/mL in all patients, indicating a blunted though not exaggerated and delayed TSH response. In eight who continued bexarotene for 24 weeks, median LT4 replacement dosage was 125 (range, 75-150) µg/day. TSH level at 30 as well as 15, 60, 90, and 120 minutes after TRH stimulation was significantly correlated with LT4 replacement dosage (ρ = -0.913, p = 0.002), whereas TSH and F-T4 basal levels at one week were not. These results suggest that pituitary hypothyroidism is responsible for bexarotene-induced CH, while TSH levels after TRH stimulation precisely reflect residual pituitary-thyroid function in patients receiving bexarotene.

Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients.

PURPOSE: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. METHODS: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. RESULTS: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9 µIU/mL, which were within the respective normal range, while serum FT3 was 2.2 ± 0.3 pg/mL. As many as 101 out of 332 (30.4%) HD patients exhibited a serum FT3 less than the normal lower limit of 2.2 pg/mL. The serum FT3/FT4 ratio correlated significantly positively with serum creatinine, and inversely with serum log CRP and total cholesterol, while it exhibited a tendency towards positive correlation with serum albumin. Multiple regression analysis, which included serum creatinine, albumin, and log CRP, simultaneously, in addition to sex, age, diabetic kidney disease or not, log HD duration, body mass index, systolic blood pressure, and Kt/V, as independent variables, revealed an independent and significant positive association of serum creatinine, but not serum albumin or CRP, with the serum FT3/FT4 ratio. CONCLUSIONS: The present study demonstrated an independent and positive correlation of serum creatinine with the serum FT3/FT4 ratio in HD patients. The lack of association of the serum FT3/FT4 ratio with serum albumin and CRP suggested the presence of a creatinine-specific mechanism to associate with serum FT3/FT4 ratio. Because of the local activation of T4 to T3 at muscle tissue, a lower muscle mass may be causatively associated with low T3 syndrome.

Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study.

INTRODUCTION: Romosozumab reportedly increases bone mineral density (BMD) potently but might adversely affect cardiovascular disease (CVD). We evaluated the efficacy of romosozumab in osteoporotic HD patients with a high risk of fracture. MATERIALS AND METHODS: This was a single-center 1-year study in Japanese HD patients. Among 96 HD romosozumab-treated HD patients with high risk of fracture, 76 HD patients completed 1 year of subcutaneous administration of romosozumab (210 mg/4 weeks) for 1 year. Romosozumab-untreated HD patients (n = 55) were also included. Changes in BMD and serum markers, together with fracture occurrence, and CVD events, were monitored. RESULTS: During romosozumab treatment of 76 HD patients, BMD time-dependently increased significantly by 15.3% ± 12.9% at the lumbar spine (L1-4), and 7.2% ± 8.3% at the femoral neck at 1 year. Serum BAP and total P1NP increased significantly and serum TRACP-5b decreased at 4 weeks. Fragility fractures occurred in three (3.8%) patients. Hypocalcemia occurred at 4-48 weeks despite the increased dosing of active vitamin-D derivatives, but without any symptom. New CVD events occurred in 5.2% of romosozumab-treated HD patients and10.9% in romosozumab-untreated HD patients. CONCLUSIONS: BMD was increased significantly during romosozumab treatment at the lumbar spine, and the femoral neck, respectively, at 1 year in HD patients. Hypocalcemia occurred but without any intolerable event. There was no apparent increase in CVD events during 1 year of study, suggesting romosozumab as a promising agent for HD patients with severe osteoporosis.

Potassium Metabolism and Management in Patients with CKD.

Potassium (K), the main cation inside cells, plays roles in maintaining cellular osmolarity and acid-base equilibrium, as well as nerve stimulation transmission, and regulation of cardiac and muscle functions. It has also recently been shown that K has an antihypertensive effect by promoting sodium excretion, while it is also attracting attention as an important component that can suppress hypertension associated with excessive sodium intake. Since most ingested K is excreted through the kidneys, decreased renal function is a major factor in increased serum levels, and target values for its intake according to the degree of renal dysfunction have been established. In older individuals with impaired renal function, not only hyperkalemia but also hypokalemia due to anorexia, K loss by dialysis, and effects of various drugs are likely to develop. Thus, it is necessary to pay attention to K management tailored to individual conditions. Since abnormalities in K metabolism can also cause lethal arrhythmia or sudden cardiac death, it is extremely important to monitor patients with a high risk of hyper- or hypokalemia and attempt to provide early and appropriate intervention.

Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease.

INTRODUCTION: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. METHODS: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57-75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. RESULTS: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3-122] vs. 25.7 [13.4-45.8] pmol/h/mL, p < 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. CONCLUSIONS: These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.

Evaluation of myostatin as a possible regulator and marker of skeletal muscle-cortical bone interaction in adults.

INTRODUCTION: Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Because circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in bone mass-skeletal muscle mass interactions. METHODS: The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. Cortical bone thickness and cancellous bone density were measured by ultrasonic bone densitometry in a health check-up survey. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle were then compared between the groups. RESULTS: The percentage of diabetic participants, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio (OR) of high myostatin levels in the LCT group compared with the NCT group was significant (OR 2.17) even after adjusting for related factors. Between the low cancellous bone density (LBD) and normal cancellous bone density (NBD) groups, significant differences were observed in the same items as between the LCT and NCT groups, but no significant differences were observed in skeletal muscle mass and blood myostatin levels. The myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass. CONCLUSIONS: A decrease in cortical bone thickness was associated with a decrease in skeletal muscle mass accompanied by an increase in the blood myostatin level. Blood myostatin may regulate the bone-skeletal muscle relationship and serve as a surrogate marker of bone metabolism, potentially linking muscle mass to bone structure.