SummaryAmong 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women.IntroductionPrior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12–24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management.MethodsThis retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥  2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk.ResultsAmong 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65–74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7–14% fractured again within 1 year depending on initial fracture site; risk rose to 15–26% within 2 years and 28–42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture.ConclusionsWe observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.Electronic supplementary materialThe online version of this article (10.1007/s00198-018-4732-1) contains supplementary material, which is available to authorized users.

We sequenced and characterized the inhibitor of apoptosis (iap) 1 gene from Aedes albopictus, designated as Aaiap1. The Aaiap1 gene rescued Spodoptera frugiperda (Sf9) cells from apoptosis when cotransfected with the Drosophila pro-apoptotic hid gene. The antiapoptotic function of the Aaiap1 gene was evaluated in the bluetongue virus (BTV)-induced apoptosis system. BTV infection induced apoptosis in vertebrate cells via the intrinsic apoptotic pathway. This was shown by the translocation of cytochrome C and the second mitochondria-derived activator of caspase (Smac, also known as DIABLO) from the mitochondria and the subsequent activation of caspase-9 and -3. Stable expression of the Aaiap1 gene in derivative baby hamster kidney cells delayed BTV-induced apoptosis by 24 h and reduced the BTV progeny yield by 10-fold. This study provides the first evidence that the mosquito AaIAP1 protein possesses antiapoptotic activity.

SummaryIn normal mice neonatal injection of staphylococcal enterotoxin B (SEB) induces tolerance in T cells that express reactive T cell receptor (TCK) V/~ regions. To determine if a T cell neonatal defect was present in MRL-Ipr/Ipr mice, 20 #g of SEB was injected intraperitoneally every other day into VBS.2 TCR transgenic and nontransgenic MR.b +/+ and MKL-Ipr/Ipr mice from birth to 2 wk of age. At 2 wk of age, V~8 + T cells were depleted, and SEB reactivity was lost, in spleen, lymph node, and thymus. These effects were equivalent in +/+ and Ipr/lpr SEB-tolerized mice. However, MILL-Ipr/Ipr mice failed to maintain neonatal tolerance. By 4 wk of age, there was a dramatic increase in T cells expressing V~8.2 in the peripheral lymph nodes of MRblpr/lt,r mice but not MRD +/+ mice. In vitro stimulation with SEB or TCR crosslinking revealed a total loss of neonatal tolerance 2 wk after cessation of SEB treatment in Ipr/Ipr mice, but not +/+ mice. The time-course of recovery of V~8 + T cells and reactivity to SEB and TCR crosslinking in the thymus of MRL-Ipr/Ipr mice was similar to that in the lymph node. Thymectomy at 2 wk of age eliminated tolerance loss in lymph nodes of MtLL-Ipr/Ipr mice at 4 wk of age, indicating that loss of peripheral tolerance was due to the emigration of untolerized T cells from the thymus. Challenge of neonatally tolerized MRb.lpr/Ipr mice with SEB (100 #g, i.p.) at 8 wk of age resulted in a dramatic onset of T cell-mediated autoimmune disease characterized by 30% weight loss and 60% morality. This indicated that loss of tolerance to SEB also occurred in vivo. In contrast, neonatally tolerized MRL-+ / + mice remained totally unresponsive to SEB challenge and did not undergo any detectable weight loss. These results suggest that there is normal induction of neonatal tolerance to SEB in lpr/Ipr mice, but that tolerance is not maintained after the tolerizing antigen is removed. This loss of neonatal tolerance can lead to severe weight loss and death on exposure to the tolerizing antigen later in life. In MRblpr/Ipr mice, which develop lymphadenopathy and autoimmune disease, extensive studies suggest that abnormal thymic development results in release of increased numbers of T cells from the thymus before tolerance induction, leading to excessive numbers of self-reactive T cells in peripheral lymphoid organs (1). This is supported by the recent finding that the Ipr gene is a mutation in the Fas antigen, which normally induces apoptosis (2--4). Although autoreactive T cells are thought to play a prominent role in the development of autoimmune disease, it is unclear if the persistence of autoreactive T cells results from a defect in induction of functional elimination either by clonal deletion or anergy induction, or from a defect in the maintenance of anergy. The present experiments were designed to study directly defects in induction and maintenance of T cell tolerance in MRL-lpr/Ipr mice. Antibodies and Reagents. Anti-CD4 (clone GK1.5), anti-CD8(clone 53-6.77), anti-CD3 (clone 145-2Cll), an...

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