Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Background: Fall risk assessment and preventive interventions are important for preventing secondary fractures after hip fracture. The aim of this study was to investigate the distribution and characteristics of Fall Risk Index-21 (FRI-21) scores based on prefracture living conditions in patients with fall-related unilateral hip fracture. Methods: This study included 95 people who had suffered a hip fracture after a fall and had undergone surgery. FRI-21, dual energy X-ray absorptiometry (DXA), and hip structure analysis/trabecular bone score based on DXA were performed within 1 week after surgery. We compared bone parameters between the two groups, which were divided according to the cutoff value of the FRI-21. We also performed cluster analysis on the components of the FRI-21 and compared the characteristics of the subgroups via analysis of variance and multiple comparison tests. Results: All participants had experienced a fall-related fracture, but 47 (49.5%) of the patients were judged to have low scores (<10) on the FRI-21. Moreover, cluster analysis revealed that the subjects were classified into three subgroups, and the characteristics of the items that constitute fall risk, namely, physical function, disease or geriatric syndrome, and environmental factors, were diverse. Conclusions These results suggest that caution is needed when interpreting the FRI-21 total score based on preoperative living conditions in post-fracture patients, as it may not adequately reflect fall risk. Considering the characteristics of the FRI-21 score in patients with hip fractures, identifying appropriate fall prevention strategies and healthcare professionals involved may be important for preventing future re-fractures.

Objectives: Physical activity to maintain bone mass and strength is important for hip fracture prevention. We aim to investigate the relationship between physical performance/activity status and bone mineral density (BMD)/hip structural analysis (HSA) parameters among postmenopausal women in Japan. Methods: Sixty-two postmenopausal women diagnosed with osteoporosis (mean age: 72.61 ± 7.43 years) were enrolled in this cross-sectional observational study. They were evaluated for BMD and HSA in the proximal femur by dual-energy X-ray absorptiometry and underwent several physical performance tests, the Geriatric Locomotive Function Scale of 25 questions (GLFS-25). Principal component analysis (PCA) was used to summarize data on the BMD/HSA parameters. Partial correlation analysis, multiple regression analysis, and structural equation modeling (SEM) were performed to investigate the relationship between physical performance/activity status and BMD/HSA parameters of the proximal femur. Results: In a partial correlation analysis adjusted for age and body mass index (BMI), GLFS-25 scores were correlated with HSA parameter (|r| = 0.260–0.396, P < 0.05). Principal component 1 (PC1) calculated by PCA was interpreted as more reflective of bone strength based on the value of BMD/HSA parameters. The SEM results showed that the model created by the 3 questions (Q13, brisk walking; Q15, keep walking without rest; Q20, load-bearing tasks and housework) of the GLFS-25 had the best fit and was associated with the PC1 score (β = −0.444, P = 0.001). Conclusions The GLFS-25 score was associated with the BMD/HSA parameter, which may reflect the bone strength of the proximal femur as calculated by PCA.

Objectives: The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. Methods: Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. Results: Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. Conclusions Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HRpQCT parameters in the tibia than in the radius, the magnitude of association is modest.

Objectives: The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. Methods: Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. Results: Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. Conclusions Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HRpQCT parameters in the tibia than in the radius, the magnitude of association is modest.

OBJECTIVES: The purpose of this study was to investigate the influences of interruption and reinitiation of monthly minodronate therapy on the bone mineral density (BMD) and bone metabolism markers in postmenopausal women with osteoporosis. METHODS: Study patients were included if they had been administered monthly minodronate therapy for ≥6 months, interrupted the therapy, and reinitiated the therapy for ≥12 months. The BMD and bone metabolism markers were assessed at 4 time points: initiation, interruption, reinitiation and 1 year after reinitiation of therapy. RESULTS: A total of 23 patients were enrolled. The mean monthly minodronate treatment period was 23.8 ± 12.9 months following a mean interruption period of 11.9 ± 5.4 months. Once increased by monthly minodronate treatment for 2 years on average, the BMD of lumbar spine and radius did not significantly decrease even after an interruption for 1 year on average. However, the BMD of the femoral neck did decrease after interruption. The BMD of the lumbar spine and radius increased further after 1 year of monthly minodronate retreatment. The BMD of the femoral neck did not change. Once decreased after the treatment for an average of 2 years followed by an interruption for 1 year, bone metabolism markers increased gradually but did not recover to baseline levels. A potent suppressive effect on bone resorption was noted. The change rate was greater for the bone formation marker procollagen 1 N-terminal propeptide. CONCLUSIONS: Monthly minodronate treatment increases BMD and reduces bone metabolism markers. The effect lessens after treatment interruptions, and can be restored by retreatment.
Bone Density ; Bone Resorption ; Female ; Femur Neck ; Humans ; Metabolism ; Osteogenesis ; Osteoporosis ; Procollagen ; Radius ; Retreatment ; Spine

OBJECTIVESThe prevalence of thoracic kyphosis is considered to increase as the population is ageing in Japan. However, little is known about the clinical and preventive significance of kyphosis. The purpose of the study is to assess the association of kyphosis with subjective poor health and functional activity in the community-dwelling Japanese elderly. The relation of kyphosis with blood pressure, as a subclinical indicator of arteriosclerosis, is also examined.

METHODSThe subjects consisted of 536 (male 241, female 295) elderly persons aged 65 years old and older. Trained examiners measured thoracic kyphosis using a flexicurve, and kyphosis index was calculated. Information on the subjects' subjective poor health and functional activity were collected through a face-to-face interview, and blood pressure was measured by a conventional method.

RESULTSIn females, their kyphosis index increased with age increased, whereas in males, there was no clear age-related change. An increased kyphosis index was associated with subjective poor health only among females. Compared with the lowest kyphosis index tertile, adjusted odds ratios for being in poor health were 5.4 (95% confidence interval: 1.1-27.4) in the middle tertile, and 6.4 (95% confidence interval: 1.3-32.1) in the highest tertile. Kyphosis index did not seem to be associated with functional activity score and blood pressure both in males and females even after adjustment.

CONCLUSIONSKyphosis is associated with subjective poor health in the community-dwelling female elderly in this study population, but not with functional activity and blood pressure both in males and females.