@article {6666, title = {Association of Fetuin-A With Incident Fractures in Community-Dwelling Older Adults: The Cardiovascular Health Study.}, journal = {J Bone Miner Res}, volume = {30}, year = {2015}, month = {2015 Aug}, pages = {1394-402}, abstract = {

Fetuin-A, a serum protein that regulates calcium mineralization, has been associated with bone mineral density (BMD) in several cross-sectional human studies, suggesting a possible beneficial effect on clinically important measures of bone health. Fetuin-A and incidence of subsequent fracture was assessed in 4714 men and women >=65 years of age. Proportional hazards models were used to estimate risk of incident hip (hospital discharge ICD-9 codes) and composite fracture (hip, pelvis, humerus, or proximal forearm; hospital discharge ICD-9 codes and Medicare claims data). A total of 576 participants had an incident hip fracture (median follow-up 11.2 years) and 768 had an incident composite fracture (median follow-up 6.9 years). In unadjusted analyses, there was no association between fetuin-A (per SD increase) and risk of hip fracture (hazard ratio [HR], 0.96; 95\% CI, 0.88 to 1.05) or composite fracture (HR, 0.99; 95\% CI, 0.92 to 1.06). Results were not significantly changed after adjustment for potential confounding variables. Analyses modeling fetuin-A in quartiles or within a subset with available BMD measures also showed no statistically significant association with risk of hip or composite fracture. Though fetuin-A was positively associated with areal BMD in partially adjusted models (total hip: β, 0.013 g/cm(2) ; 95\% CI, 0.005 to 0.021; femoral neck: β, 0.011 g/cm(2) ; 95\% CI, 0.004 to 0.018; and lumbar spine: β, 0.007 g/cm(2) ; 95\% CI, 0.001 to 0.028), these associations were no longer significant after further adjustment for BMI and in final multivariate models. In this large sample of community-dwelling older adults, a small positive association between fetuin-A and areal BMD appeared attributable to confounding variables and we found no evidence of an association between fetuin-A and risk of clinical fracture.

}, keywords = {Adult, Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Bone Density, Cross-Sectional Studies, Female, Follow-Up Studies, Fractures, Bone, Humans, Incidence, Male, Models, Biological}, issn = {1523-4681}, doi = {10.1002/jbmr.2475}, author = {Fink, Howard A and B{\r u}zkov{\'a}, Petra and Garimella, Pranav S and Mukamal, Kenneth J and Cauley, Jane A and Kizer, Jorge R and Barzilay, Joshua I and Jalal, Diana I and Ix, Joachim H} } @article {8627, title = {Association of skeletal muscle mass, kidney disease and mortality in older men and women: the cardiovascular health study.}, journal = {Aging (Albany NY)}, volume = {12}, year = {2020}, month = {2020 11 02}, pages = {21023-21036}, abstract = {

Low muscle mass (sarcopenia) is a prevalent and major concern in the aging population as well as in patients with chronic kidney disease (CKD). We hypothesized that sarcopenia is an independent predictor of incident and progressive CKD and increased mortality in older men and women (>=65 years) from the Cardiovascular Health Study. Sarcopenia was defined by bioimpedance-estimated skeletal muscle mass index (SMI) as a continuous variable and categorically (normal, class I, and class II). Cox regression hazard ratios (HRs) estimated the risk of incident and prevalent CKD and mortality in individuals with and without CKD. Low SMI was associated with increased prevalence of CKD in men (p<0.001), but lower prevalence of CKD in women (p=0.03). Low muscle mass was not associated with incident CKD or rapid CKD progression (>3 ml/minute/1.73m/year decline in eGFR) in men, but was associated with lower risk of incident CKD in women ([adjusted RR=0.69, 95\% (0.51,0.94)]. Low muscle mass (class II) was independently associated with higher mortality only in men [(adjusted HR=1.26, 95\% (1.05,1.50)]. Neither definition of sarcopenia was associated with mortality in men or women with CKD. Further studies are needed to understand the mechanisms by which sarcopenia contributes to higher mortality in aging men.

}, issn = {1945-4589}, doi = {10.18632/aging.202135}, author = {Kruse, Nicholas T and B{\r u}zkov{\'a}, Petra and Barzilay, Joshua I and Valderr{\'a}bano, Rodrigo J and Robbins, John A and Fink, Howard A and Jalal, Diana I} } @article {9635, title = {Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures.}, journal = {J Bone Miner Res}, year = {2024}, month = {2024 Jan 04}, abstract = {

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Tr{\o}ndelag Health Study) with circulating proteomics data (aptamer-based 5~K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 {\texttimes} 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.

}, issn = {1523-4681}, doi = {10.1093/jbmr/zjad011}, author = {Austin, Thomas R and Fink, Howard A and Jalal, Diana I and T{\"o}rnqvist, Anna E and B{\r u}zkov{\'a}, Petra and Barzilay, Joshua I and Lu, Tianyuan and Carbone, Laura and Gabrielsen, Maiken E and Grahnemo, Louise and Hveem, Kristian and Jonasson, Christian and Kizer, Jorge R and Langhammer, Arnulf and Mukamal, Kenneth J and Gerszten, Robert E and Nethander, Maria and Psaty, Bruce M and Robbins, John A and Sun, Yan V and Skogholt, Anne Heidi and {\r A}svold, Bj{\o}rn Olav and Valderr{\'a}bano, Rodrigo J and Zheng, Jie and Richards, J Brent and Coward, Eivind and Ohlsson, Claes} }