Physical Frailty May Predict 2-Year Prognosis in Elderly Patients With Acute Myocardial Infarction　- A Report From the FLAGSHIP Study.

BACKGROUND: Elderly patients with acute myocardial infarction (AMI) are a high-risk population for heart failure (HF), but the association between physical frailty and worsening prognosis, including HF development, has not been documented extensively.Methods and Results: As part of the FLAGSHIP study, we enrolled 524 patients aged ≥70 years hospitalized for AMI and capable of walking at discharge. Physical frailty was assessed using the FLAGSHIP frailty score. The primary outcome was a composite outcome of all-cause death and HF rehospitalization within 2 years after discharge. The secondary outcome was all-cause death and HF rehospitalization. After adjusting for confounders, physical frailty showed a significant association with an increased risk of the composite outcome (hazard ratio [HR]=2.09, 95% confidence interval [CI]: 1.03-4.22, P=0.040). The risk of HF rehospitalization increased with physical frailty, but the association was not statistically significant (HR=2.14, 95% CI: 0.84-5.44, P=0.110). Physical frailty was not associated with an increased risk of all-cause death (HR=1.45, 95% CI: 0.49-4.26, P=0.501). CONCLUSIONS: The findings suggest that physical frailty assessment serves as a stratifying tool to identify high-risk populations for post-discharge clinical events among ambulant elderly patients with AMI.

Gap between the prevalence of and consultation rate for lumbopelvic pain in postnatal Japanese women.

BACKGROUND: We aimed to assess the prevalence of lumbopelvic pain (LPP), including low back pain (LBP) and/or pelvic girdle pain (PGP), consultation rate, and desire for treatment of postnatal Japanese women. METHODS: We performed a cross-sectional study of 98 postnatal Japanese women within 1 year of childbirth. We retrospectively evaluated the prevalence of LBP before and during pregnancy and the prevalence of LPP after childbirth using a self-administered questionnaire. We used the distribution of pain to differentiate LBP and/or PGP after childbirth and its intensity was assessed using a visual analogue scale. The effects of LPP on daily life were assessed using the Oswestry disability index (ODI). In addition, we assessed the consultation rate for LPP and the desire to consult a healthcare professional, using self-administered questionnaires. RESULTS: The prevalence of LPP after childbirth was 66%. Women with a history of LBP before and during pregnancy were more likely to have LPP following childbirth (both P < 0.001). The consultation rate among the postnatal women with LPP was 9%, but 56% of the women wished to consult a healthcare professional. The ODI score was significantly higher in postnatal women who wanted to consult a healthcare professional than in those who did not (P < 0.01). CONCLUSIONS: Two thirds of the postnatal Japanese women who participated in this study had LPP, but the consultation rate was low. However, more than half of these women had the desire to consult a healthcare professional.

Dyspnea and outcome expectations are associated with physical activity in persons with pneumoconiosis: a cross-sectional study.

BACKGROUND: There are various reports on factors associated with physical activity in patients with chronic respiratory diseases. However, there are no studies on the relationship between physical activity and psychological or environmental factors. In this study, we investigated the relationship between physical activity and psychological and environmental factors using questionnaires for patients with pneumoconiosis. METHODS: This cross-sectional study included patients with pneumoconiosis who underwent a pneumoconiosis health examination in 2019. A self-administered questionnaire was used to conduct the study. Physical activity was evaluated using the International Physical Activity Questionnaire, and subjective symptoms [dyspnea and quality of life (QOL)], environmental factors (environment around home and life space), psychological factors (depression, stage of change, self-efficacy, decisional balance, and outcome expectations), and others (e.g., experience with pulmonary rehabilitation) were investigated. RESULTS: The number of respondents in the study was 185 (men: 171, women: 14). Age, dyspnea, stage of change, self-efficacy, outcome expectations, QOL, depression, decisional balance, and life space were significantly correlated with physical activity. In the multivariate analysis, outcome expectations and dyspnea were extracted as independent factors. In the path analysis, outcome expectations and dyspnea had a direct influence on physical activity. Dyspnea directly impacted not only physical activity but also outcome expectations, stage of change, QOL, life space, and depression. CONCLUSIONS: Dyspnea and outcome expectations were associated with physical activity in patients with pneumoconiosis. To improve physical activity in pneumoconiosis patients, it was suggested that it may be necessary to improve dyspnea and promote an understanding of physical activity.

The effects of skin cold stimulation on quadriceps muscle activity during walking in older adults.

Purpose: Given that walking speed declines with ageing and decreasing walking speed restricts activities of daily living (ADL), it is important for the old to maintain walking speed in order to prevent affecting ADL. Although skin cold stimulation (SCS) facilitates instantaneous muscle activity, which occurs during walking, the effects of SCS on muscle activity during walking remain unclear. Thus, the present study aimed to investigate the effect of SCS during walking in older adults.Methods: Seventeen community-dwelling healthy older adults (73 ± 6 years old) participated in this study. Walking speed at a comfortable pace and the electromyographic (EMG) activity of the vastus lateralis (VL) and biceps femoris (BF) were measured. SCS, which maintains the skin temperature at 25 °C, was applied to the front of the thigh during the procedures. Walking speed, root mean square EMG (rmsEMG) and mean power frequency (MPF) were compared under SCS and control conditions.Results: SCS significantly increased the walking speed (p < 0.01) and the rmsEMG of the vastus lateralis (p = 0.032). No change in the rmsEMG of the BF was observed, and SCS had no effect on MPF of both the VL and BF. Furthermore, a significant relationship was observed between these changes (r = 0.619, p = 0.042).Conclusion: SCS increased the EMG activity of the VL while increasing walking speed. Our results suggest that SCS is an effective strategy that can be included in daily life in order to improve walking ability of older adults.

Age differences in reactive strategies and execution time during choice stepping with visual interference.

PURPOSE: We aimed to explore the effects of visual interference from a flanker task on a reactive strategy and execution speed of choice stepping among young and older adults. METHODS: Twenty-two healthy young (21.9 ± 1.4 years) and 21 older participants (72.6 ± 4.9 years) were instructed to execute forward stepping as quickly and accurately as possible on the side indicated by a central arrow (←left vs. right→) of a visual cue during a neutral condition. During a flanker condition, participants were additionally required to ignore flanker arrows on each side of the central arrow (→→→→→ congruent or incongruent →→←→→). Errors in the direction of the initial weight transfer [anticipatory postural adjustment (APA) errors], step execution time, and divided phases (reaction, APA, and swing phases) were measured from the data of vertical force. RESULTS: Incongruence had larger effects on step execution times and APA phase in older adults than in young adults, while incongruence had smaller effects on reaction phase in older adults than in young adults. Step execution times were prolonged for trials with APA errors relative to trials without those in both groups. Only older adults showed that step execution times during trials with APA errors increased prominently in the incongruent condition as compared to the other conditions. CONCLUSION: Older adults might have a tendency to make hastier judgments, and might be vulnerable to potential motor program errors caused by an interference effect. Composite measurement of inhibition and stepping in a functional context may increase discriminative ability for age-related deficits in postural control.

Analysis of Choice Stepping with Visual Interference Can Detect Prolonged Postural Preparation in Older Adults with Mild Cognitive Impairment at High Risk of Falling.

BACKGROUND/AIMS: We aimed to clarify postural control deficits in older adults with mild cognitive impairment (MCI) at high risk of falling by addressing the inhibitory process. METHODS: This study involved 376 community-dwelling older adults with MCI. Participants were instructed to execute forward stepping on the side indicated by the central arrow while ignoring the 2 flanking arrows on each side (→→→→→, congruent, or →→←→→, incongruent). Initial weight transfer direction errors [anticipatory postural adjustment (APA) errors], step execution times, and divided phases (reaction, APA, and swing phases) were measured from vertical force data. Participants were categorized as fallers (n = 37) and non-fallers (n = 339) based on fall experiences in the last 12 months. RESULTS: There were no differences in the step execution times, swing phases, step error rates, and APA error rates between groups, but fallers had a significantly longer APA phase relative to non-fallers in trials of the incongruent condition with APA errors (p = 0.005). Fallers also had a longer reaction phase in trials with the correct APA, regardless of the condition (p = 0.01). CONCLUSION: Analyses of choice stepping with visual interference can detect prolonged postural preparation as a specific falling-associated deficit in older adults with MCI.

Association of Nutritional Risk With Gait Function and Activities of Daily Living in Older Adult Patients With Hip Fractures.

OBJECTIVE: To investigate the association of nutritional risk with gait function and activities of daily living (ADLs) in older adult patients with hip fractures. METHODS: The retrospective data of older adult patients diagnosed with hip fractures who visited the recovery-phase rehabilitation ward between January 2019 and December 2022 were reviewed. Nutritional risk was evaluated using the Geriatric Nutritional Risk Index; gait function and ADLs were assessed using the modified Harris Hip Score subitem and Functional Independence Measure, respectively. Multivariate linear regression and path analysis with structural equation modeling were used to examine the factors associated with ADLs and the associations among the study variables. RESULTS: This study included 206 participants (172 females and 34 males; mean age, 85.0±7.3 years). In the multivariate analysis, gait function (ß=0.488, p<0.001), cognitive function (ß=0.430, p<0.001), and surgery (ß=-0.143, p<0.001) were identified as independent factors. Pathway analysis revealed that nutritional risk was not directly correlated with ADLs but was directly associated with gait and cognitive functions. Gait and cognitive functions, in turn, were directly related to ADLs. CONCLUSION: Nutritional risk was found to be associated with ADLs through an intermediary of gait and cognitive functions.

Protective effects of hachimijiogan (HJG), a Japanese Kampo medicine, on cancer cachectic muscle wasting in mice.

Myogenesis is required to generate skeletal muscle tissue and to maintain skeletal muscle mass. Decreased myogenesis under various pathogenic conditions results in muscular atrophy. Through a small screening of Japanese traditional (Kampo) medicines, hachimijiogan (HJG) was shown to promote the myogenic differentiation of C2C12 myoblasts through the upregulation of myogenin. In tumor-bearing cancer-cachectic mice, HJG was also found to have a protective effect against cancer-cachectic muscle wasting. This effect was significant when HJG was administered in combination with aerobic exercise by treadmill running. Moreover, HJG ameliorated the cellular atrophy of C2C12 myotubes induced by treatment with conditioned medium derived from a colon-26 cancer cell culture. In addition, HJG suppressed H2O2-dependent myotube atrophy, suggesting that HJG could reverse the atrophic phenotypes by eliminating reactive oxygen species.

[Factors associated with fear of falling among community-dwelling elderly adults without reduced performance in instrumental activities of daily living].

AIM: The purpose of this study was to examine factors related to fear of falling (FOF) in elderly adults who showed no reduced performance regarding independent instrumental activities of daily living (IADL). METHODS: A total of 119 elderly adults participated in the study (mean age, 75.7±7.2 years, women, n=60). We investigated the prevalence of FOF, anamnesis, medications, body pain, and history of falls, the Geriatric Depression Scale, International Physical Activity Questionnaire, Life-Space Assessment (LSA). The Timed Up and Go test (TUG) and one-legged standing time were measured to evaluate physical performance. Participants were divided into elderly adults with FOF (FOF group) and those without FOF (non-FOF group). The unpaired t-test or chi-square test was used for group comparisons. Multiple logistic regression analysis was then performed to examine the factors associated with FOF. RESULTS: The prevalence of FOF was 51.3% overall. The FOF group had a higher prevalence of anamnesis, body pain, and history of falls than the non-FOF group. The FOF group had lower LSA scores, longer durations on the TUG, and shorter durations on the one-legged standing test than the non-FOF group. On multiple logistic regression analysis, LSA (total score, 120 points) was significantly associated with FOF (odds ratio: 0.96, 95% confidence interval=0.93-0.99). CONCLUSION: Fear of falling was significantly associated with life space in community-dwelling elderly adults who showed no reduced performance regarding IADL. In future, it will be necessary to clarify any possible causal relationship by longitudinal investigations.

IL-6 plays an essential role in neutrophilia under inflammation.

In the present study, we explored the involvement of interleukin-6 (IL-6) in neutrophilia under inflammatory conditions. The neutrophil count in the peripheral blood was high in arthritic monkeys, and anti-IL-6 receptor antibody reduced neutrophil counts to normal levels. IL-6 injection into normal monkeys significantly increased neutrophil counts in the blood 3h after injection. The expression of cluster of differentiation (CD) 162 on circulating neutrophils was reduced by IL-6 injection. IL-6 treatment in vitro did not affect CD162 expression on neutrophils from human blood. In IL-6-treated monkeys, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in plasma were clearly elevated. IL-8 and GM-CSF treatment in vitro reduced cell-surface CD162 expression on human neutrophils, and moreover, increased soluble CD162 expression in the cell supernatant. The addition of IL-6 into human whole peripheral blood induced IL-8 production and reduced CD162 expression on neutrophils. Furthermore, IL-8 and GM-CSF augmented mRNA expression of a disintegrin and metalloprotease like domain 10 (ADAM10) in neutrophils. Knock-down of ADAM10 by siRNA in neutrophil-like HL-60 cells partially reversed the expression of CD162 reduced by GM-CSF and IL-8 on HL-60 cells. In conclusion, IL-6 induced neutrophilia and reduced CD162 expression on neutrophils in inflammation.

Anti-IL-6 receptor antibody causes less promotion of tuberculosis infection than anti-TNF-α antibody in mice.

Objective. Our aim was to investigate the effects of IL-6 blockade on the progression of Mycobacterium tuberculosis (TB) and compare them with those of TNF-α blockade in mice. Methods. Mice were intravenously infected with TB and injected with antibodies. Survival was monitored and histological and immunological studies were carried out. Results. All anti-IL-6R Ab-treated mice and 8 of 10 control mice survived until sacrificed 224 days after TB challenge, whereas anti-TNF-α Ab-treated mice all died between 120 and 181 days. Anti-IL-6R Ab-treated mice exhibited no significant differences in TB CFU in organs, including the lungs, and no deterioration in histopathology compared to control mice at 4 weeks. In contrast, anti-TNF-α Ab-treated mice exhibited increased TB CFU and greater progression of histopathological findings in organs than control mice. Spleen cells from anti-TNF-α Ab-treated mice had decreased antigen-specific response in IFN-γ release and proliferation assays. The results in anti-IL-6R Ab-treated mice suggest that spleen cell responses were decreased to a lesser degree. Similar results were obtained in IL-6 knockout (KO) mice, compared with TNF receptor 1 (TNFR1) KO and TNFR1/IL-6 double KO (DKO) mice. Conclusion. IL-6R blockade promotes the progression of TB infection in mice far less than TNF-α blockade.

Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production.

We have reported that serum IL-6 level was related with the degree of anemia in monkey collagen-induced arthritis (CIA). In this study, we examined whether IL-6 blockade ameliorated an anemia in monkey CIA. CIA was induced by twice immunization of bovine type II collagen with adjuvant. When anemia became evident, anti-IL-6 receptor antibody, tocilizumab was intravenously injected once a week for 4 weeks. Controls received PBS in a same manner. Hematological and biochemical parameters were measured regularly and serum hepcidin-25 levels were measured by SELDI-TOF mass spectrometry. Moreover, hepcidin mRNA induction in Hep3B cells by serum from arthritic monkeys was examined by real-time PCR. Administration of tocilizumab rapidly decreased CRP levels and improved iron-deficient anemia within 1 week. Tocilizumab induced rapid but transient reduction in serum hepcidin-25. Hepcidin mRNA expression was more potently induced by serum from arthritic monkey and this was inhibited by the addition of tocilizumab. Blockade of IL-6 signaling rapidly improved anemia in monkey arthritis via the inhibition of IL-6-induced hepcidin production.

c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs.

Although active vitamin D drugs have been used for the treatment of osteoporosis, how the vitamin D receptor (VDR) regulates bone cell function remains largely unknown. Using osteoprotegerin-deficient mice, which exhibit severe osteoporosis due to excessive receptor activator of NF-kappaB ligand/receptor activator of NF-kappaB (RANKL/RANK) stimulation, we show herein that oral treatment of these mice with 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] inhibited bone resorption and prevented bone loss, suggesting that VDR counters RANKL/RANK signaling. In M-CSF-dependent osteoclast precursor cells isolated from mouse bone marrow, 1alpha,25(OH)2D3 potently and dose-dependently inhibited their differentiation into multinucleate osteoclasts induced by RANKL. Among signaling molecules downstream of RANK, 1alpha,25(OH)2D3 inhibited the induction of c-Fos protein after RANKL stimulation, and retroviral expression of c-Fos protein abrogated the suppressive effect of 1alpha,25(OH)2D3 on osteoclast development. By screening vitamin D analogs based on their c-Fos-suppressing activity, we identified a new analog, named DD281, that inhibited bone resorption and prevented bone loss in ovariectomized mice, more potently than 1alpha,25(OH)2D3, with similar levels of calcium absorption. Thus, c-Fos protein is an important target of the skeletal action of VDR-based drugs, and DD281 is a bone-selective analog that may be useful for the treatment of bone diseases with excessive osteoclastic activity.

[Relationship between exercise capacity and physical fitness in elderly people with chronic heart failure and chronic respiratory failure].

AIM: The purpose of this study was to examine the relationship between exercise capacity and physical fitness in healthy elderly people and elderly subject with chronic respiratory failure and chronic heart failure, and whether that relationship differs depending on level of exercise capacity. METHODS: Measurements were made in 15 healthy elderly people, 17 people with chronic respiratory failure, and 15 people with chronic heart failure in the incremental shuttle walking test, timed up and go test, functional reach test, one leg balance test, grip force, knee extension force, half-squat test, step test, and sitting trunk flexion. The correlation between incremental shuttle walking test distance and other variables was compared between the disease groups, and between groups with incremental shuttle walking test distance under and over 450 m, which was the index of physical capacity for heart transplant. RESULTS: In the disease groups, more physical fitness variables correlated with exercise capacity than in the healthy elderly group. The under-450 m group had poorer balance, muscular endurance, and agility than the over-450 m group. In the under-450 m group, exercise capacity was correlated with balance, muscle power, and agility. CONCLUSIONS: In elderly people with chronic respiratory failure and chronic heart failure, exercise capacity is influenced by various factors of physical performance. Training to improve physical fitness may be necessary for elderly people with incremental shuttle walking test distance of below 450 m.

[Does age-related change affect the short-term postoperative improvement of physical functions and abilities in compressive cervical myelopathy?].

AIM: This study aimed to clarify whether age-related changes affect the short-term postoperative improvement of physical functions and abilities in compressive cervical myelopathy by comparing elderly and non-elderly cervical myelopathy. METHODS: A total of 56 patients with cervical myelopathy who were candidates for surgery (63.1+/-11.5 years; 40 men, 16 women) were investigated. Written consent to participate in this study was obtained from all participants. The following items were assessed before and/or a month postoperatively; six basic characteristics (Hattori's classification, symptom duration, comorbidity, Pavlof ratio, dynamic instability of cervical spine and cervical intramedullary high intensity change); one motor and one sensory function in the lower and upper extremities, respectively; two walking abilities; one manual dexterity. After division into the elderly group (> or =65 years) and non-elderly group (65 years>). basic characteristics, physical functions and abilities were compared between the two groups. RESULTS: The elderly group consisted of 27 participants (72.7+/-5.2 years; 16 men, 11 women) and the non-elderly group consisted of 29 participants (54.1+/-8.1 years; 24 men, 5 women). In the 6 preoperative characteristics, the rate of having comorbidity in the elderly group (63.0%) was significantly greater than the non-elderly group (27.6%). Most comobidities were orthopedic disorders. Preoperative motor function in the lower extremity in the elderly group was significantly inferior to the non-elderly group, whereas the improvement rate based on preoperative finding at a month postoperatively was equal to the non-elderly group. Preoperative walking abilities were significantly inferior to the non-elderly group, although their improvement rates were equal to or significantly greater than the non-elderly group. Moreover, preoperative upper extremity motor function and manual dexterity in the elderly group were equal to those in the non-elderly group, and their improvement rates were also equal. CONCLUSIONS: Preoperative motor function in the lower extremity and walking abilities in elderly cases of compressive cervical myelopathy were significantly inferior to non-elderly cases of cervical myelopathy, although their improvement rates based on preoperation at one month postoperatively were equal to or significantly greater than non-elderly cases of cervical myelopathy; therefore age-related change is not a directly negative factor for short-term postoperative improvement.

Role of the BDNF-TrkB pathway in KCC2 regulation and rehabilitation following neuronal injury: A mini review.

In most mature neurons, low levels of intracellular Cl- concentrations ([Cl-]i) are maintained by channels and transporters, particularly the K+-Cl- cotransporter 2 (KCC2), which is the only Cl- extruder in most neurons. Recent studies have implicated KCC2 expression in the molecular mechanisms underlying neuronal disorders, such as spasticity, epilepsy and neuropathic pain. Alterations in KCC2 expression have been associated with brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB). The present review summarizes recent progress regarding the roles of Cl- regulators in immature and mature neurons. Moreover, we focus on the role of KCC2 regulation via the BDNF-TrkB pathway in spinal cord injury and rehabilitation, as prior studies have shown that the BDNF-TrkB pathway can affect both the pathological development and functional amelioration of spinal cord injuries. Evidence suggests that rehabilitation using active exercise and mechanical stimulation can attenuate spasticity and neuropathic pain in animal models, likely due to the upregulation of KCC2 expression via the BDNF-TrkB pathway. Moreover, research suggests that such rehabilitation efforts may recover KCC2 expression without the use of exogenous BDNF.

Identifying the Effects of Assistive and Resistive Guidance on the Gait of Elderly People Using a Smart Walker.

Progression of technology has expanded applications of smart walkers in clinical fields. However, it is essential to investigate the effects of different types of gait guidance in order to introduce smart walkers more widely throughout these fields. The purpose of this study was to identify the effects of assistive and resistive guidance on the gait of elderly people using a smart walker. Gait parameters, surface electromyography of lower limb muscles, and trunk acceleration were measured. The assistive guidance force significantly increased gait speed, step length, and cadence while increasing trunk acceleration variability. The same amount of resistive guidance force did not change gait parameters; instead, however, it restrained the speed-dependent increase of trunk acceleration variability in the mediolateral direction. An analysis of muscle activity suggested that the lower limb muscle activity could be increased by varying gait parameters including speed, step length, and cadence.

Gait-phase-dependent control using a smart walker for physical training.

Falling has become a key factor that affects the quality of life of the elderly. Currently, the use of a few rehabilitation robots can contribute to the restoration of balance. In this paper, a walker-based rehabilitation robot with a gait-phasedependent control algorithm is proposed to promote dynamic balance in the elderly. It has unique characteristics in that the level of the walker to resist the propulsion force exerted by a user can vary depending on the gait-phase that is estimated using the interaction force between the robot and the user. The robot efficiently improves the muscle power of various muscle groups of the user. Experiments with three young subjects were conducted to validate the effectiveness of the walker with the gait-phase-dependent control algorithm.

Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production.

We explored the mechanism for the increase of blood IL-6 level after anti-IL-6 receptor (IL-6R) antibody injection. First, we examined whether anti-IL-6R antibody stimulates IL-6 production. Single injection of tocilizumab (anti-IL-6R antibody) in monkeys with collagen-induced arthritis (CIA) caused a marked increase in blood IL-6 and IL-6R levels, but did not increase IL-6 mRNA and IL-6R mRNA expression in liver, spleen, lymph nodes, synovium or whole blood 1, 3 and 7 days later. This suggests that tocilizumab did not induce IL-6 and IL-6R production. Second, we investigated whether anti-IL-6R antibody releases IL-6 from IL-6 complexes in the blood. When plasma from CIA monkeys was incubated with tocilizumab, the IL-6 concentration was not affected. Finally, we studied whether anti-IL-6R antibody affects the clearance of IL-6 from the blood. When MR16-1 (anti-mouse IL-6R antibody) was injected into IL-6-deficient mice continuously infused with human IL-6, blood human IL-6 levels significantly increased. These results suggest that the elevation of blood IL-6 after the administration of anti-IL-6R antibody is the result of inhibition of the clearance of IL-6 due to IL-6R blockade, and that it is not the result of induction of IL-6 production or release of IL-6 from complexes.

Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model.

To understand the contribution of IL-6/IL-6R to subchondral bone and bone marrow abnormality in RA patients and the effects of tocilizumab on those abnormalities, we evaluated early change in a collagen-induced arthritis (CIA) monkey model with or without a single administration of tocilizumab. Six CIA cynomolgus monkeys received tocilizumab and 3 CIA monkeys received vehicle only. Their interphalangeal joints were analyzed using HE, silver impregnation (SI), or immunohistochemistry (RANKL) staining. The number of osteoclasts increased in the arthritis control but was suppressed in the tocilizumab-treated animals. Osteoblast/stromal cells of the arthritis control monkeys were of monolayer, while in the tocilizumab-treated monkeys, the cells were multi-layer or differentiated osteoblasts, and the meshwork of the reticulum fibers showed recovery in the SI. Hematopoietic marrow was replaced by interstitial fluid and reticulum fibers were eliminated in the arthritic model but showed recovery in the tocilizumab-treated animals. RANKL showed overproduction with arthritis and suppressed with tocilizumab treatment. The evidence indicates that IL-6/IL-6R is involved in subchondral bone and bone marrow change in RA patients. Tocilizumab treatment recovered changes in the CIA monkeys as a result of the co-differentiation between the osteoclasts and the osteoblast/stramal cells, at least partially through the suppression of RANKL overproduction.