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ID PMID Title PublicationDate abstract
28981461 Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxi 2017 Oct 5 Abstract: Reductive stress (RS) is the counterpart oxidative stress (OS), and can occur in response to conditions that shift the redox balance of important biological redox couples, such as the NAD⁺/NADH, NADP⁺/NADPH, and GSH/GSSG, to a more reducing state. Overexpression of antioxidant enzymatic systems leads to excess reducing equivalents that can deplete reactive oxidative species, driving the cells to RS. A feedback regulation is established in which chronic RS induces OS, which in turn, stimulates again RS. Excess reducing equivalents may regulate cellular signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism, and thus, contribute to the development of some diseases in which NF-κB, a redox-sensitive transcription factor, participates. Here, we described the diseases in which an inflammatory condition is associated to RS, and where delayed folding, disordered transport, failed oxidation, and aggregation are found. Some of these diseases are aggregation protein cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer's disease, and metabolic syndrome, among others. Moreover, chronic consumption of antioxidant supplements, such as vitamins and/or flavonoids, may have pro-oxidant effects that may alter the redox cellular equilibrium and contribute to RS, even diminishing life expectancy.
28866631 Association of gender-specific risk factors in metabolic and cardiovascular diseases: an N 2018 Jan In the present cross-sectional study, based on National Health and Nutrition Examination Survey (NHANES, 2007-2010) cohorts, various risk factors for metabolic syndrome (MetS) and cardiovascular diseases (CVDs) were analyzed (n=12,153). The variables analyzed include, demographics, comorbidities associated with MetS or CVD, behavioral and dietary factors, while the primary endpoints were the prevalence of MetS and CVD. The prevalence of MetS and CVD was slightly higher in males as compared with females (42.50% and 7.65% vs 41.29% and 4.13%, respectively). After controlling for confounding factors, advanced age, family history of diabetes mellitus (DM), overweight, and obesity were significantly associated with the likelihood of MetS, irrespective of gender differences. In males, the diagnosis of prostate cancer and regular smoking were additional risk factors of MetS, whereas, advanced age, family history of heart attack or angina, health insurance coverage, diagnosis of rheumatoid arthritis or depression, obesity and low calorie intake were identified as risk factors for CVD. In addition to the above risk factors, higher physical activity and vitamin D insufficiency were also found to increase the risk of CVD in females. Furthermore, obesity was a higher risk factor for MetS than CVD. Emerging risk factors for CVD identified in this study has major clinical implications. Of interest is the correlation of higher physical activity and the risk of CVD in women and the role of depression and lower calorie intake in general population.
28828392 Thermal Stability as a Determinant of AAV Serotype Identity. 2017 Sep 15 Currently, there are over 150 ongoing clinical trials utilizing adeno-associated viruses (AAVs) to target various genetic diseases, including hemophilia (AAV2 and AAV8), congenital heart failure (AAV1 and AAV6), cystic fibrosis (AAV2), rheumatoid arthritis (AAV2), and Batten disease (AAVrh.10). Prior to patient administration, AAV vectors must have their serotype, concentration, purity, and stability confirmed. Here, we report the application of differential scanning fluorimetry (DSF) as a good manufacturing practice (GMP) capable of determining the melting temperature (T(m)) for AAV serotype identification. This is a simple, rapid, cost effective, and robust method utilizing small amounts of purified AAV capsids (∼25 μL of ∼10(11) particles). AAV1-9 and AAVrh.10 exhibit specific T(m)s in buffer formulations commonly used in clinical trials. Notably, AAV2 and AAV3, which are the least stable, have varied T(m)s, whereas AAV5, the most stable, has a narrow T(m) range in the different buffers, respectively. Vector stability was dictated by VP3 only, specifically, the ratio of basic/acidic amino acids, and was independent of VP1 and VP2 content or the genome packaged. Furthermore, stability of recombinant AAVs differing by a single basic or acidic amino acid residue are distinguishable. Hence, AAV DSF profiles can serve as a robust method for serotype identification of clinical vectors.
28779592 Psoralidin suppresses osteoclastogenesis in BMMs and attenuates LPS-mediated osteolysis by 2017 Oct Psoralidin is a metabolic product from the seed of psoraleacorylifolia, possessed anti-inflammatory and immunomodulatory effects. We speculated that psoralidin might impact osteoclastogenesis and bone loss. By using both in vitro and in vivo studies, we observed psoralidin strongly inhibited RANKL induced osteoclast formation during preosteoclast cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. At the molecular level, by using MAPKs specific inhibitors (U-0126, SB-203580 and SP-600125) we demonstrated that psoralidin markedly abrogated the phosphorylation of p38, ERK, JNK. Moreover, the RANKL induced NF-κB/p65 phosphorylation and I-κB degradation were significantly inhibited by psoralidin. Further, psoralidin significantly suppressed osteoclastogenesis marker genes of TRAP, Cathepsin K and OSCAR. These were accompanied by the decreased expression of c-Fos and NFATc1 transcription factors. Consistent with in vitro results, our in vivo and serologic studies showed psoralidin inhibited lipopolysaccharide induced bone resorption by suppressing the inflammatory cytokines: TNF-α and IL-6 expression, as well as the ratio of RNAKL : OPG. These results collectively suggested that psoralidin could represent a novel therapeutic strategy for osteoclast-related disorders, such as rheumatoid arthritis and postmenopausal osteoporosis.
28480161 Multiple cavities with halo sign in a case of invasive pulmonary aspergillosis during ther 2017 A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine. Human herpes virus 6 (HHV-6) variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA), and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patient's general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients.
28444576 Expression of CCR6 on B cells in systemic lupus erythematosus patients. 2017 Jun B cells are known to play a dominant pathogenic role in autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. In recent times, the chemokine receptor CCR6 and its cognate ligand CCL20 have been shown to play a role in the fundamental kinetics of germinal centres and B cell responses. As CCR6 is found on B cells and is upregulated after activation, we investigated the expression of CCR6 on naive, pre-germinal centre (GC), GC/plasma cell and memory B cells in peripheral B cells of SLE patients and healthy controls using flow cytometry. Pre-germinal centre B cells are found in lower proportions and the expression of CCR6 is increased on B cells of SLE patients, suggesting a role for the chemokine pair in the pathogenesis of the disease. Further studies are needed to explore these preliminary results.
28413980 Therapeutic Applications of Liposomal Based Drug Delivery and Drug Targeting for Immune Li 2017 Immune-based inflammatory diseases involve immune related dysregulation in different sites of body, which includes rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atherosclerosis, etc. Advancements in molecular research have facilitated investigation of their pathogenesis that is involved in inflammatory cytokines cells and several genes. The available drug therapy provides suboptimal therapeutic effects and higher adverse effects. Emergence of liposomal systems of the drugs meant for the above mentioned disease has gained broader importance due to their high treatment efficacy by means of optimal therapeutic drug delivery. Beyond the conventional liposomal formulations, evolution of second generation liposomes including stealth liposomes, cationic liposomes, immuno-liposomes, etc. has gained tremendous attention owing to their drug target potential, diagnostic importance and imaging in treatment of above mentioned immune mediated inflammatory disorders.
28411808 Validation of a new method by nano-liquid chromatography on chip tandem mass spectrometry 2017 Jul 1 Microfluidic liquid chromatography coupled to a nanoelectrospray source ion trap mass spectrometry was used for the absolute and simultaneous quantitation of C3f and the V65 vitronectin fragment in serum. The method was first carefully optimized and then validated in serum biological matrix. Stable isotopes for the two biomarkers of interest were used as stable isotope labeled peptide standards. A weighted 1/x(2) quadratic regression for C3f and a weighted 1/x quadratic regression for the V65 vitronectin peptide were selected for calibration curves. Trueness (with a relative bias <10%), precision (repeatability and intermediate precision <15%) and accuracy (risk <15%) of the method were successfully demonstrated. The linearity of results was validated in the concentration range of 2.5-200ng/mL for C3f and 2.5-100ng/mL for the V65 vitronectin fragment. Serum samples (n=147) classified in 7 groups [(healthy volunteers, OA with 5 grades of severity and rheumatoid arthritis (RA) patients] were analyzed with our new quantitative method. Our data confirm that C3f and the V65 vitronectin fragment are biomarkers of OA severity, but also that C3f fragment is further related to OA severity whereas the V65 vitronectin fragment is more related to early OA detection.
27579490 Involvement of CX3CL1 in the Migration of Osteoclast Precursors Across Osteoblast Layer St 2017 Jul The trigger for bone remodeling is bone resorption by osteoclasts. Osteoclast differentiation only occurs on the old bone, which needs to be repaired under physiological conditions. However, uncontrolled bone resorption is often observed in pro-inflammatory bone diseases, such as rheumatoid arthritis. Mature osteoclasts are multinuclear cells that differentiate from monocyte/macrophage lineage cells by cell fusion. Although Osteoclast precursors should migrate across osteoblast layer to reach bone matrix before maturation, the underlying mechanisms have not yet been elucidated in detail. We herein found that osteoclast precursors utilize two routes to migrate across osteoblast layer by confocal- and electro-microscopic observations. The osteoclast supporting activity of osteoblasts inversely correlated with osteoblast density and was positively related to the number of osteoclast precursors under the osteoblast layer. Osteoclast differentiation was induced by IL-1ß, but not by PGE(2) in high-density osteoblasts. Osteoblasts and osteoclast precursors expressed CX3CL1 and CX3CR1, respectively, and the expression of CX3CL1 increased in response to interleukin-1ß. An anti-CX3CL1-neutralizing antibody inhibited the migration of osteoclast precursors and osteoclast differentiation. These results strongly suggest the involvement of CX3CL1 in the migration of osteoclast precursors and osteoclastogenesis, and will contribute to the development of new therapies for bone diseases. J. Cell. Physiol. 232: 1739-1745, 2017. © 2016 Wiley Periodicals, Inc.
27056250 Feasibility and efficacy of a robotic device for hand rehabilitation in hemiplegic stroke 2017 Mar OBJECTIVE: The purpose of the study was to evaluate the feasibility and efficacy of robot-assisted hand rehabilitation in improving arm function abilities in sub-acute hemiplegic patients. DESIGN: Randomized controlled pilot study. SETTING: Inpatient rehabilitation centers. PARTICIPANTS: Thirty hemiplegic stroke patients (Ashworth spasticity index <3) were recruited and randomly divided into a Treatment group (TG) and Control group (CG). INTERVENTIONS: Patients in the TG received intensive hand training with Gloreha, a hand rehabilitation glove that provides computer-controlled, repetitive, passive mobilization of the fingers, with multisensory feedback. Patients in the CG received the same amount of time in terms of conventional hand rehabilitation. MAIN OUTCOME MEASURES: Hand motor function (Motricity Index, MI), fine manual dexterity (Nine Hole Peg Test, NHPT) and strength (Grip and Pinch test) were measured at baseline and after rehabilitation, and the differences, (Δ) mean(standard deviation), compared between groups. Results Twenty-seven patients concluded the program: 14 in the TG and 13 in the CG. None of the patients refused the device and only one adverse event of rheumatoid arthritis reactivation was reported. Baseline data did not differ significantly between the two groups. In TG, ΔMI 23(16.4), ΔNHPT 0.16(0.16), ΔGRIP 0.27(0.23) and ΔPINCH 0.07(0.07) were significantly greater than in CG, ΔMI 5.2(9.2), ΔNHPT 0.02(0.07), ΔGRIP 0.03(0.06) and ΔPINCH 0.02(0.03)] ( p=0.002, p=0.009, p=0.003 and p=0.038, respectively). CONCLUSIONS: Gloreha Professional is feasible and effective in recovering fine manual dexterity and strength and reducing arm disability in sub-acute hemiplegic patients.
26853723 Trans-presentation of interleukin-15 by interleukin-15 receptor alpha is dispensable for t 2017 Jul Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is required for the survival and activation of memory CD8(+)T cells, natural killer (NK) cells, innate lymphoid cells, macrophages and dendritic cells. IL-15 is implicated in the pathogenesis of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis and autoimmune type 1 diabetes (T1D). IL-15 receptor (IL-15R) consists of a specific α chain, the β chain that is shared with IL-2R and the common γ chain. IL-15 is unique in the manner in which it binds and signals through its receptor subunits. IL-15 that is complexed with IL-15Rα binds to the βγ receptor complex present on the responding cell to mediate its biological effects through a process referred to as trans-presentation. The trans-presented IL-15 is essential to mediate the biological effects on T lymphocytes and NK cells. Here we show that IL-15, but not IL-15Rα, is required for the development of spontaneous and virus-induced T1D, viral clearance and for antigen cross-presentation to CD8(+) T lymphocytes. Our findings provide insight into the complexities of IL-15 signalling in the initiation and maintenance of CD8(+) T cell-mediated immune responses.
29289276 Diseases of the lips. 2017 Sep Heath care providers should be comfortable with normal as well as pathologic findings in the lips, because the lips are highly visible and may display clinical manifestations of local, as well as systemic inflammatory, allergic, irritant, and neoplastic alterations. Fortunately, the lips are easily accessible. The evaluation should include a careful history and physical examination, including visual inspection, as well as palpation of the lips and an examination of associated cervical, submandibular, and submental nodes. Pathologic and microscopic studies, as well as a review of medications, allergies, and habits, may further highlight possible etiologies. Many lip conditions, including premalignant changes, are relatively easy to treat, when the abnormalities are detected early; however, advanced disease and malignancies are challenging for both the patient and clinician. Treatment should be focused on eliminating potential irritants or allergens and treatment of the primary dermatosis. In this paper we review physiologic variants as well as pathologic conditions of the lips.
28853298 Analyses of hair and salivary cortisol for evaluating hypothalamic-pituitary-adrenal axis 2017 Nov Although many studies have shown that patients with autoimmune disease present a hypoactive hypothalamic-pituitary-adrenal axis (HPA), controversial results have been described. Our objective was to study HPA axis activity in women with autoimmune disease compared to healthy women. Therefore, we analyzed salivary cortisol over the course of a day, and hair cortisol concentrations from the three preceding months, from 65 women divided into two groups: healthy women (n = 30), with a mean age of 44.70 ± 11.65 years; and women with autoimmune disease (n = 35), with a mean age of 48.26 ± 9.04 years. The latter group comprises women with systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and systemic sclerosis (SSc). Perceived stress and psychopathological symptomatology were also evaluated. Autoimmune disease group scored higher on the somatization subscale SCL-90-R and lower on the anxiety subscale than the control group. Regarding HPA axis activation, the area under curve for cortisol levels during the day was higher for the autoimmune disease group. In addition, higher cortisol levels in hair were found in the group with autoimmune disease. Our findings show greater short and long-term HPA axis activity in women with autoimmune disease than in healthy women.
29065905 Severe intestinal dysbiosis is prevalent in primary Sjögren's syndrome and is associated 2017 Oct 24 BACKGROUND: Altered microbial composition of the intestine, commonly referred to as dysbiosis, has been associated with several autoimmune diseases including primary Sjögren's syndrome (pSS). The aims of the current study were to study the intestinal microbial balance in pSS and to identify clinical features associated with dysbiosis. METHODS: Forty-two consecutive pSS patients and 35 age-matched and sex-matched control subjects were included in the study in an open clinic setting. Stool samples were analyzed for intestinal dysbiosis using a validated 16S rRNA-based microbiota test (GA-map™ Dysbiosis Test; Genetic Analysis, Oslo, Norway). Dysbiosis and severe dysbiosis were defined in accordance with the manufacturer's instructions. Patients were evaluated with regard to disease activity (European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and Clinical ESSDAI (ClinESSDAI)). In addition, patients were examined for laboratory and serological features of pSS as well as fecal calprotectin levels. Furthermore, patients were investigated regarding patient-reported outcomes for pSS (EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)) and irritable bowel syndrome (IBS)-like symptoms according to the Rome III criteria. RESULTS: Severe dysbiosis was more prevalent in pSS patients in comparison to controls (21 vs 3%; p = 0.018). Subjects with pSS and severe dysbiosis had higher disease activity as evaluated by the ESSDAI total score (13 vs 5; p = 0.049) and the ClinESSDAI total score (12 vs 5; p = 0.049), lower levels of complement component 4 (0.11 vs 0.17 g/L; p = 0.004), as well as higher levels of fecal calprotectin (110 vs 33 μg/g; p = 0.001) compared to the other pSS patients. In contrast, severe dysbiosis among pSS patients was not associated with disease duration, IBS-like symptoms, or the ESSPRI total score. CONCLUSIONS: Severe intestinal dysbiosis is a prevalent finding in pSS and is associated both with clinical and laboratory markers of systemic disease activity as well as gastrointestinal inflammation. Further studies are warranted to elucidate a potential causative link between dysbiosis and pSS.
28668260 [Amyopathic dermatomyositis (DM) with anti-MDA5 antibodies, associated with bullous pemphi 2017 Oct BACKGROUND: The inflammatory myopathies are a heterogeneous group of muscle diseases and comprise polymyositis, dermatomyositis (DM), myopathies associated with cancers, necrotising myositis and inclusion body myositis. DM occasionally exhibits few or no muscular signs: i.e. hypomyopathic/amyopathic DM. Anti-MDA5 dermatomyositis (DM) is a rare form of dermatomyositis that is frequently amyopathic; the prognosis is linked mainly to pulmonary involvement. PATIENTS AND METHODS: A 69-year-old woman treated for mucosa-associated lymphoid tissue (MALT) gastric lymphoma was referred for a bullous eruption. Based on the investigations performed, a diagnosis was made of bullous pemphigoid. At the same time, amyopathic dermatomyositis was discovered together with interstitial lung disease. Systemic steroids were introduced in combination with rituximab. A favourable outcome was achieved. DISCUSSION: Anti-MDA5 dermatomyositis must be considered systematically in all cases of pulmonary involvement associated with cutaneous signs of dermatomyositis, in which no muscular involvement is generally seen. This condition accounts for up to 7% of DM and carries a severe prognosis due to pulmonary involvement.
28249724 Time-course of ultrasound abnormalities of major salivary glands in suspected Sjögren's s 2018 Mar OBJECTIVE: To evaluate whether major salivary-gland ultrasonography (SGUS) abnormalities change over time in patients with suspected primary Sjögren's syndrome (pSS) during the natural course of the disease. METHODS: We studied patients with suspected pSS who were included in the Brittany cohort of suspected pSS and underwent SGUS at least twice, as part of the routine diagnostic workup done at baseline then at least 1 year later as an additional investigation deemed appropriate by the physician. The evaluation criteria were the semi-quantitative SGUS score (0-4) for each parotid and submandibular gland, the highest SGUS score among the four glands, and the sum of SGUS scores for the four glands. These scores were compared in patients with and without pSS according to the workup at baseline, and their changes over time were assessed. RESULTS: Of 49 included patients, 29 received a diagnosis of pSS at baseline; none of the remaining 20 patients was diagnosed with pSS at either evaluation. The mean (SD) sum of SGUS scores at baseline was 8.9 (5.6) in patients with and 2.1 (2.9) in those without pSS (P<0.01). Mean time between SGUSs was 1.9 (1.6) years. None of the evaluation criteria changed between the two SGUSs in the overall population, pSS group, or group without pSS. Similar results were found in the subgroup with recent-onset symptoms. CONCLUSION: SGUS abnormalities assessed using a semi-quantitative score did not change significantly during a follow-up of nearly 2 years after an initial evaluation for suspected pSS.
28202864 Clinical Presentation of Tubulointerstitial Nephritis Caused by Amyloid Light-chain Amyloi 2017 We report a 70-year-old woman with Sjögren's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low-molecular-weight proteins. Based on these clinical presentations, interstitial nephritis due to Sjögren's syndrome was strongly suspected. Unexpectedly, renal pathology revealed amyloid light-chain (AL) lambda-type depositions predominantly in the vasculatures with severe tubulointerstitial damage. Concentrated urine immunofixation was positive for Bence Jones lambda-type monoclonal proteins. Given the involvement in other organs, systemic AL amyloidosis was diagnosed. The patient underwent chemotherapy, but hemodialysis was ultimately instituted. It should be remembered that renal amyloidosis occurs as a clinical presentation of interstitial nephritis.
28704602 Defective Early B Cell Tolerance Checkpoints in Sjögren's Syndrome Patients. 2017 Nov OBJECTIVE: Central and peripheral B cell tolerance checkpoints are defective in many patients with autoimmune diseases, but the functionality of each discrete checkpoint has not been assessed in patients with Sjögren's syndrome (SS). We undertook this study to assess this functionality in SS patients. METHODS: Using a polymerase chain reaction-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD19+CD21(low) CD10+IgM(high) CD27- newly emigrant/transitional B cells and CD19+CD21+CD10-IgM+CD27- mature naive B cells from 5 SS patients. RESULTS: We found that the frequencies of newly emigrant/transitional B cells expressing polyreactive antibodies were significantly increased in SS patients compared to those in healthy donors, revealing defective central B cell tolerance in SS patients. Frequencies of mature naive B cells expressing autoreactive antibodies were also significantly increased in SS patients, thereby illustrating an impaired peripheral B cell tolerance checkpoint in these patients. CONCLUSION: Defective counterselection of developing autoreactive B cells observed in SS patients is a feature common to many other autoimmune diseases and may favor the development of autoimmunity by allowing autoreactive B cells to present self antigens to T cells.
28148696 Attitudes and Approaches for Withdrawing Drugs for Children with Clinically Inactive Nonsy 2017 Mar OBJECTIVE: To assess the attitudes and strategies of pediatric rheumatology clinicians toward withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA). METHODS: Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision making and approaches for withdrawing medications for inactive nonsystemic JIA. Data were analyzed using descriptive statistics. RESULTS: Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision making for withdrawing medications were the duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of rheumatoid factor-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6-12 months of inactive disease before stopping methotrexate (MTX) or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children receiving combination MTX-biologic therapy, 63% of respondents preferred stopping MTX first. Most clinicians reported using imaging only seldom or sometimes to guide decision making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation. CONCLUSION: Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes.
28474780 The Effect of Abaloparatide-SC on Fracture Risk Is Independent of Baseline FRAX Fracture P 2017 Aug Daily subcutaneous (SC) injections of the investigational drug abaloparatide-SC (80 mcg) for 18 months significantly decrease the risk of vertebral and nonvertebral fracture compared with placebo in postmenopausal women. We examined the efficacy of abaloparatide-SC as a function of baseline fracture risk, assessed using the FRAX tool. Baseline clinical risk factors (age, body mass index [BMI], prior fracture, glucocorticoid use, rheumatoid arthritis, and smoking) were entered into country-specific FRAX models to calculate the 10-year probability of major osteoporotic fractures, with or without femoral neck bone mineral density (BMD). The interaction between probability of a major osteoporotic fracture and treatment efficacy was examined by a Poisson regression. A total of 821 women randomized to placebo and 824 women to abaloparatide-SC, mean age 69 years in both groups, were followed for up to 2 years. At baseline, the 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.3% to 57.5% (mean 13.2%). Treatment with abaloparatide-SC was associated with a 69% (95% confidence interval [CI] 38-85%) decrease in major osteoporotic fracture (MOF) and a 43% (95% CI 9-64%) decrease in any clinical fracture compared with placebo. For all outcomes, hazard ratios tended to decrease (ie, greater efficacy) with increasing fracture probability. Whereas the interaction approached significance for the outcome of any fracture (p = 0.11), there was no statistically significant interaction for any of the fracture outcomes. Similar results were noted when FRAX probability was computed without BMD. Efficacy of abaloparatide-SC to decrease the risk of major osteoporotic fracture or any clinical fracture in postmenopausal women with low BMD and/or prior fracture appears independent of baseline fracture probability. © 2017 American Society for Bone and Mineral Research.