CTRP3 is Significantly Decreased in Patients with Primary Hyperparathyroidism and Closely Related with Osteoporosis

Abstract

Background Adipokines derived from adipocytes are one of the important factors that act as circulating regulators of bone metabolism. Complement C1q/tumor necrosis factor-related protein-3 (CTRP3), a paralog of adiponectin, is are member of the CTRP superfamily. The aim of this study was to investigate the role of serum CTRP3 in the development of osteoporosis in patients with primary hyperparathyroidism.

Methods This study included 53 patients with diagnosed primary hyperparathyroidism and 30 healthy controls. Laboratory tests for the diagnosis of primary hyperparathyroidism and serum levels of CTRP3 measured for all patients. Bone mineral density was obtained on lumbar spine 1 and 4 by dual energy X-ray absorptiometry.

Results Serum CTRP3 levels were lower in patients with primary hyperparathyroidism than in the control group (p<0.001). In addition, primary hyperparathyroidism patients are were divided into two groups as, with and without osteoporosis; the levels of CTRP3 were lower in patients with osteoporosis than in patients without osteoporosis (p=0.004). In logistic regression analysis, only CTRP3 levels independently determined the patients to be osteoporosis (p<0.05). According to this analysis, decreased CTRP3 (per 1 ng/mL) levels were found to increase the risk of patients for osteoporosis by 6.9%. When the CTRP3 cut-off values were taken as 30 ng/mL, it determined osteoporosis with 76.4% sensitivity and 73.2% specificity. CTRP3 and urine calcium levels were independently associated with T score in dual energy X-ray absorptiometry.

Conclusions CTRP3 levels were significantly decreased in patients with primary hyperparathyroidism, and it is also related to osteoporosis.

Key words

adiponectin - bone mineral density - adipokine - osteopenia - dual energy X-ray absorptiometry

• References

• 1 Lumachi F, Camozzi V, Ermani M. et al. Lumbar spine bone mineral density changes in patients with primary hyperparathyroidism according to age and gender. Ann NY Acad Sci 2007; 1117: 362-366
• 2 Imanishi Y. Secondary osteoporosis. Secondary osteoporosis by primary hyperparathyroidism. Clin Calcium 2018; 28: 1627-1634
• 3 Sitges-Serra A, García L, Prieto R. et al. Effect of parathyroidectomy for primary hyperparathyroidism on bone mineral density in postmenopausal women. Br J Surg 2010; 97: 1013-1019
• 4 Poulos SP, Hausman DB, Hausman GJ. The development and endocrine functions of adipose tissue. Mol Cell Endocrinol 2010; 323 pp 20-34
• 5 Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Current Biology 1998; 8: 335-340
• 6 Wong GW, Wang J, Hug C. et al. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci USA 2004; 101: 10302-10307
• 7 Ghaib R, Waters P, Roumenina LT. et al. C1q and its growing family Immunobiology. 2007; 212: 253-266
• 8 Li Y, Wright GL, Peterson JM. C1q/TNF-Related Protein 3 (CTRP3) Function and Regulation. Compr Physiol 2017; 7: 863-878
• 9 Liu Y, Song CY, Wu SS. et al. Novel adipokines and bone metabolism. Int J Endocrinol 2013; 2013: 895045
• 10 Maeda T, Jikko A, Abe M. et al. Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes. J Cell Physiol 2006; 206: 537-544
• 11 Yokohama-Tamaki T, Maeda T, Tanaka TS. et al. Functional analysis of CTRP3/cartducin in Meckel’s cartilage and developing condylar cartilage in the fetal mouse mandible. J Anat 218: 517-533
• 12 Kim JY, Min JY, Baek JM. et al. CTRP3 acts as a negative regulator of osteoclastogenesis through AMPK-c-Fos-NFATc1 signaling in vitro and RANKL-induced calvarial bone destruction in vivo. Bone 2015; 79: 242-251
• 13 Karsenty G, Wagner EF, Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development, Dev Cell. 2002; Apr 2: 389-406
• 14 Xu ZH, Zhang X, Xie H. et al. Serum CTRP3 level is associated with osteoporosis in postmenopausal women. Exp Clin Endocrinol Diabetes 2018; Oct 126: 559-563
• 15 Bilezikian JP, Brandi ML, Eastell R. et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the fourth international workshop. J Clin Endocrinol Metab 2014; Oct 99: 3561-3569
• 16 Bushinsky DA, Monk RD. Electrolyte quintet: Calcium. Lancet 1998; 352: 306-311
• 17 Li X, Jiang L, Yang M. et al. CTRP3 modulates the expression and secretion of adipokines in 3T3-L1 adipocytes. Endocr J 2014; 61: 1153-116
• 18 Kim JY, Min JY, Baek JM. et al. CTRP3 acts as a negative regulator of osteoclastogenesis through AMPK-c-Fos-NFATc1 signaling in vitro and RANKL-induced calvarial bone destruction in vivo. Bone 2015; 79: 242-251
• 19 Akiyama H, Furukawa S, Wakisaka S. et al. Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through both extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways. FEBS J 2006; 273: 2257-2263
• 20 Murayama MA, Kakuta S, Maruhashi T. et al. CTRP3 plays an important role in the development of collagen-induced arthritis in mice. Biochem Biophys Res Commun 2014; 443: 42-48
• 21 Noda S, Onoda N, Ohira M. Secondary osteoporosis. Surgical treatment for patients with secondary osteoporosis. Clin Calcium 2018; 28: 1671-1677
• 22 Mendoza-Moreno F, Díez-Alonso M, Ovejero-Merino E. et al. Analysis of the increase in bone mineral density after surgical treatment of primary hyperparathyroidism. J Clin Densitom 2018; Nov 9. pii S1094-S6950 30189-30186
• 23 Peterson JM, Wei Z, Wong GW. C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output. J Biol Chem 2010; 285: 39691-39701
• 24 Peterson JM, Seldin MM, Wei Z. et al. CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism. Am J Physiol Gastrointest Liver Physiol 2013; 305: G214-G224
• 25 Yoo HJ, Hwang SY, Hong HC. et al. Implication of progranulin and C1q/TNF-related protein-3 (CTRP3) on inflammation and atherosclerosis in subjects with or without metabolic syndrome. PLoS One 2013; 8: e55744
• 26 Sumbul HE, Koc AS. The abdominal aortic intima-media thickness increases in patients with primary hyperparathyroidism. Exp Clin Endocrinol Diabetes 2019; 127: 387-395 10.1055/a-0664-7820