OR01-4 Low Plasma Leucine-Rich Repeat-Containing 17 (LRRc17) Level Is an Independent and Additive Risk Factor for Prevalent Vertebral Fractures in Postmenopausal Women

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR01-Osteoporosis: What You Had, What You Lost, and What You Gain
Translational
Friday, April 1, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 12:30 PM
Room 157 (BCEC)

Outstanding Abstract Award
Namki Hong*1, Beom-Jun Kim2, Chong Hwa Kim3, Ki-Hyun Baek4, Yong-Ki Min5, Deog-Yoon Kim6, Seung Hun Lee2, Jung-Min Koh2, Moo-Il Kang7 and Yumie Rhee1
1Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, South Korea, 2Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, 3Department of Internal Medicine, Sejong General Hospital, Bucheon city, 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, Seoul, Korea, Seoul, South Korea, 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, South Korea, 6Department of Nuclear Medicine, Kyunghee University School of Medicine, Seoul, South Korea, 7Seoul St. Mary’s Hospital, The Catholic University of Korea, College of Medicine, Seoul, South Korea
Abstract: Although bone mineral density (BMD) and several clinical risk factors (CRF) have been identified to predict the risk of osteoporotic fracture (OF), the ability to predict the risk of OF is still suboptimal. Leucine-rich repeat-containing 17 (LRRc17) was known to act as a negative regulator of receptoractivator of NF-kB ligand (RANKL) induced osteoclast differentiation, and thus to play a protective role in bone metabolism.(1) In this case-control study, we aimed to investigate whether decreased circulating plasma LRRc17 level can serve as an independent and additive risk factor for prevalent OF, even after divided into vertebral fracture (VF) and non-vertebral fracture (non-VF). Among 532 consecutive postmenopausal women without any disease or medications that could affect bone metabolism, 102 cases with OF and 102 age and body mass index (BMI)-matched controls (mean age 63.2 years) were enrolled. Morphological VF (n=49) and non-VF (i.e., forearm, humerus, hip, and pelvis; n=60) were identified by lateral thoracolumbar radiographs and an interviewer-assisted questionnaire, respectively. Plasma LRRc17 level was measured using LRRc17 ELISA kit (MyBioSource, San Diego, USA)and natural log-transformed LRRc17 were used due to right-skewed distribution. BMD was measured at lumbar spine and proximal femur by dual-energy X-ray absorptiometry (Lunar Prodigy, Madison, WI). Median plasma LRRc17 levels were significantly lower in subjects with any prevalent OF (117.5 vs. 197.3 pg/ml, P< 0.001), VF (93.2 vs. 172.4 pg/ml, P = 0.002), and non-VF (124.5 vs. 206.9 pg/ml, P = 0.008) compared to their controls. The prevalence of OF was increased in stepwise fashion from the highest LRRc17 tertile (LRRc17 ≥ 228.5 pg/ml, 33.8%) to the lowest (LRRc17 < 95.6 pg/ml, 63.2%). Each one log unit decrease of LRRc17 was associated with increased risk of prevalent OF (Odds ratio [OR] 1.47 [1.10-1.96], P=0.009) and VF (OR 2.43 [1.39-4.23], P=0.002) but only increased tendency with non-VF (OR 1.29 [0.90-1.85], P=0.162) in multivariable logistic models adjusted for CRF and BMD. Adding the information regarding plasma LRRc17 levels to CRF and BMD significantly improved discrimination of prevalent VF patients according to comparison of area under receiver operating characteristics curves (0.71 [0.60-0.82] to 0.81 [0.71-0.90], P=0.036), category-free net reclassification improvement (NRI 0.79, 0.37-1.21, P <0.001), and integrated discrimination improvement (IDI 0.13, 0.06-0.20, P < 0.001) but the improvement was not significant for discriminating non-VF. Our findings suggest that decreased plasma LRRc17 level may be an independent and additive risk factor for prevalent OF, particularly in spine, rather than non-vertebral skeletal sites.

(1) Kim et al., J Biol Chem. 2009 May 29;284(22):15308-16.

Nothing to Disclose: NH, BJK, CHK, KHB, YKM, DYK, SHL, JMK, MIK, YR

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