Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. ) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication.

Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38,971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31,213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation 1-year postsurgery was investigated. During a median follow-up time of 3.1 (interquartile range [IQR], 1.7 to 4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (hazard ratio [HR] 1.26; 95% CI, 1.05 to 1.53; and HR 1.32; 95% CI, 1.18 to 1.47; respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. © 2018 American Society for Bone and Mineral Research.

Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.

Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention-totreat analysis. Time periods corresponding to the FLS hospitals were used for the non-FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow-up time of 2.2 years (range 0-6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73-0.92, p = .001), corresponding to a 3-year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients.

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