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Gout and the Risk of Non-vertebral Fracture.

ABSTRACT: Prior studies suggest an association between osteoporosis, systemic inflammation, and pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Conflicting findings exist on the association between hyperuricemia and osteoporosis. Furthermore, it remains unknown whether gout, a common inflammatory arthritis, affects fracture risk. Using data from a US commercial health plan (2004-2013), we evaluated the risk of non-vertebral fracture (ie, forearm, wrist, hip, and pelvis) in patients with gout versus those without. Gout patients were identified with ?2 diagnosis codes and ?1 dispensing for a gout-related drug. Non-gout patients, identified with ?2 visits coded for any diagnosis and ?1 dispensing for any prescription drugs, were free of gout diagnosis and received no gout-related drugs. Hip fracture was the secondary outcome. Fractures were identified with a combination of diagnosis and procedure codes. Cox proportional hazards models compared the risk of non-vertebral fracture in gout patients versus non-gout, adjusting for more than 40 risk factors for osteoporotic fracture. Among gout patients with baseline serum uric acid (sUA) measurements available, we assessed the risk of non-vertebral fracture associated with sUA. We identified 73,202 gout and 219,606 non-gout patients, matched on age, sex, and the date of study entry. The mean age was 60 years and 82% were men. Over the mean 2-year follow-up, the incidence rate of non-vertebral fracture per 1,000 person-years was 2.92 in gout and 2.66 in non-gout. The adjusted hazard ratio (HR) was 0.98 (95% confidence interval [CI] 0.85-1.12) for non-vertebral fracture and 0.83 (95% CI 0.65-1.07) for hip fracture in gout versus non-gout. Subgroup analysis (n?=?15,079) showed no association between baseline sUA and non-vertebral fracture (HR?=?1.03, 95% CI 0.93-1.15), adjusted for age, sex, comorbidity score, and number of any prescription drugs. Gout was not associated with a risk of non-vertebral fracture. Among patients with gout, sUA was not associated with the risk of non-vertebral fracture. © 2016 American Society for Bone and Mineral Research.

SUBMITTER: Kim SC

PROVIDER: S-EPMC5292077 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Gout and the Risk of Non-vertebral Fracture.

Kim Seoyoung C SC Paik Julie M JM Liu Jun J Curhan Gary C GC Solomon Daniel H DH

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20160906 2

Prior studies suggest an association between osteoporosis, systemic inflammation, and pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Conflicting findings exist on the association between hyperuricemia and osteoporosis. Furthermore, it remains unknown whether gout, a common inflammatory arthritis, affects fracture risk. Using data from a US commercial health plan (2004-2013), we evaluated the risk of non-vertebral fracture (ie, forearm, wrist, hip, and pelvis) in patients with go ...[more]

PMID: 27541696

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Project description:UNLABELLED:Daily teriparatide injections have been shown to reduce vertebral and non-vertebral fractures. Here, we demonstrate that the magnitude of fracture risk reduction is independent of baseline fracture probability assessed by FRAX. INTRODUCTION:Daily administration of 20 or 40 ?g teriparatide has been shown to significantly decrease the risk of vertebral and non-vertebral fracture compared with placebo. The aim of the present study was to evaluate fracture risk assessed at baseline using the FRAX® tool and to determine the efficacy of teriparatide as a function of baseline fracture risk. METHODS:One thousand six hundred thirty-seven postmenopausal women in the pivotal phase three trial, randomly assigned to receive placebo (n?=?544), teriparatide 20 ?g per day (n?=?541) or teriparatide 40 ?g per day (n?=?552), were studied. Baseline clinical risk factors were entered into country-specific FRAX models to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. Because there was no difference in effect of 20 and 40 ?g teriparatide daily on fracture occurrence, the two active groups were merged. The interaction between probability of a major fracture and treatment efficacy was examined by Poisson regression. RESULTS:The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.2-67.2 %. Treatment with teriparatide was associated with a 37 % decrease in all non-vertebral fractures (95 % CI 10-56 %) and a 56 % decrease in low-energy non-vertebral fractures (95 % CI 24-75 %) compared with placebo. The risk of morphometric vertebral fractures decreased significantly by 66 % (95 % CI 50-77 %). Hazard ratios for the effect of teriparatide on the fracture outcome did not change significantly with increasing fracture probability (p?>?0.30). Similar findings were noted for the interaction when BMD was excluded from the FRAX model, or when probability of hip fracture was used as the marker of baseline risk. CONCLUSION:We conclude that teriparatide significantly decreases the risk of non-vertebral and morphometric vertebral fractures in women by a similar extent, irrespective of baseline fracture probability.

Project description:INTRODUCTION: Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. METHODS: Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. RESULTS: Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50-64 years, 53.2% were aged 65-74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score -1 or above), 37.4% were osteopenic (T-score -1.1 to -2.4) and 27.6% osteoporotic (T-score -2.5 or lower). Humerus (n=103, 31%), radius-ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score <or=-2.5, or low BMI, or with more than one prior non-vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some guidelines suggest that anti-resorptive therapy should be reserved for patients with DXA-proven osteoporosis. However, patients who have one or more prior vertebral fractures (prevalent at the time of their non-vertebral fracture) would also become candidates for anti-resorptive therapy-which would have not been the case had their vertebral fracture status not been known. Overall in this study, 8.9% of patients are likely to have had a change in management by virtue of their underlying vertebral deformity status. In other words, 11 patients who present with a non-vertebral fracture would need to undergo vertebral morphometry in order to identify one patient who ought to be managed differently. CONCLUSIONS: Our results support the recommendation to perform vertebral morphometry in patients who are referred for DXA after experiencing a non-vertebral fracture. Treatment decisions will then better reflect any given patient's future absolute fracture risk. The 'Number Needed to Screen' if vertebral morphometry is used in this way would be seven to identify one patient with vertebral deformity, and 14 to identify one patient with two or more vertebral deformities. Although carrying out MXA will increase radiation exposure for the patient, this increased exposure is significantly less than would be obtained if X-rays of the dorso-lumbar spine were obtained.

Project description:BACKGROUND:Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain, impedes respiratory function, lower the quality of life, and increases the risk of new fractures and deaths. Various medications have been prescribed to prevent a secondary fracture, but few study summarized their effects. Therefore, we investigated their effects on preventing subsequent OVCF via meta-analyses of randomized controlled trials. METHODS:Electronic databases, including MEDLINE, EMBASE, CENTRAL, and Web of Science were searched for published randomized controlled trials from June 2015 to June 2019. The trials that recruited participants with at least one OVCF were included. We assessed the risk of bias of every study, estimated relative risk ratio of secondary OVCF, non-vertebral fracture, gastrointestinal complaints and discontinuation due to adverse events. Finally, we evaluated the quality of evidence. RESULTS:Forty-one articles were included. Moderate to high quality evidence proved the effectiveness of zoledronate (Relative Risk, RR: 0.34; 95% CI, 0.17-0.69, p?=?0.003), alendronate (RR: 0.54; 95% CI: 0.43-0.68; p <?0.0001), risedronate (RR: 0.61; 95% CI: 0.51-0.73; p?<?0.0001), etidronate (RR, 0.50; 95% CI, 0.29-0.87, p?<?0.01), ibandronate (RR: 0.52; 95% CI: 0.38-0.71; p <?0.0001), parathyroid hormone (RR: 0.31; 95% CI: 0.23-0.41; p?<?0.0001), denosumab (RR, 0.41; 95% CI, 0.29-0.57; p?<?0.0001) and selective estrogen receptor modulators (Raloxifene, RR: 0.58; 95% CI: 0.44-0.76; p?<?0.0001; Bazedoxifene, RR: 0.66; 95% CI: 0.53-0.82; p =?0.0002) in preventing secondary fractures. Moderate quality evidence proved romosozumab had better effect than alendronate (Romosozumab vs. alendronate, RR: 0.64; 95% CI: 0.49-0.84; p =?0.001) and high quality evidence proved that teriparatide had better effect than risedronate (risedronate vs. teriparatide, RR: 1.98; 95% CI: 1.44-2.70; p <?0.0001). CONCLUSION:Zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone, denosumab and selective estrogen receptor modulators had significant secondary prevention effects on OVCF. Moderate quality evidence proved romosozumab had better effect than alendronate. High quality evidence proved PTH had better effect than risedronate, but with higher risk of adverse events.

Project description:Recent studies suggest a positive association between obstructive sleep apnea (OSA), a disorder associated with intermittent hypoxia and sleep fragmentation, and derangements in bone metabolism. However, no prospective study to date has investigated the association between OSA and fracture risk in women. We conducted a prospective study examining the relation between OSA and risk of incident vertebral fracture (VF) and hip fracture (HF) in the Nurses' Health Study. History of physician-diagnosed OSA was assessed by self-reported questionnaires. A previous validation study demonstrated high concordance between self-reports and medical record identification of OSA. OSA severity was further categorized according to the presence or absence of self-reported sleepiness. Self-reports of VF were confirmed by medical record review. Self-reported HF was assessed by biennial questionnaires. Cox proportional-hazards models estimated the hazard ratio for fracture according to OSA status, adjusted for potential confounders, including BMI, physical activity, calcium intake, history of osteoporosis, and falls, and use of sleep medications. Among 55,264 women without prior history of fracture, physician-diagnosed OSA was self-reported in 1.3% in 2002 and increased to 3.3% by 2012. Between 2002 and 2014, 461 incident VF cases and 921 incident HF cases were documented. The multivariable-adjusted hazard ratio (HR) for confirmed VF for women with history of OSA was 2.00 (95% CI, 1.29-3.12) compared with no OSA history, with the strongest association observed for OSA with daytime sleepiness (HR 2.86; 95% CI, 1.31-6.21). No association was observed between OSA history and self-reported HF risk (HR 0.83; 95% CI, 0.49-1.43). History of OSA is independently associated with higher risk of confirmed VF but did not have a statistically significant association with self-reported HF in women. Further research is warranted in understanding the role of OSA and intermittent hypoxia in bone metabolism and health that may differ by fracture site. © 2020 American Society for Bone and Mineral Research (ASBMR).

Project description:Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n?=?15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n?=?21,701) and clinical vertebral fracture (n?=?5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]?=?3%) was associated with higher vBMD (??=?0.22, p?=?1.9?×?10-8 ) and decreased risk of radiographic vertebral fracture (odds ratio [OR]?=?0.75; false discovery rate [FDR] p?=?0.01). In 1p36.12, rs12742784 (MAF?=?21%) was associated with higher vBMD (??=?0.09, p?=?1.2?×?10-10 ) and decreased risk of clinical vertebral fracture (OR?=?0.82; FDR p?=?7.4?×?10-4 ). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (??=?0.28, FDR p?=?0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (??=?0.12, FDR p?=?1.7?×?10-3 , functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.

Dataset Information

Gout and the Risk of Non-vertebral Fracture.

Publications

Gout and the Risk of Non-vertebral Fracture.

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