New Biological Markers of Bone Metabolism in Osteoporosis Treatment

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Endocrinol Metab 2016;31:400-401

http://dx.doi.org/10.3803/EnM.2016.31.3.400 pISSN 2093-596X · eISSN 2093-5978

Editorial

New Biological Markers of Bone Metabolism in Osteoporosis Treatment

Sun Wook Cho

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Osteoporosis is a chronic skeletal disorder characterized by low bone mass and poor bone quality. It is a major public health concern in aging society and requires life-long treatment for preventing fragility bone fracture. One of the main limitations in treatment of osteoporosis is the lack of smart surrogate mark- ers that reflect the status of bone quality and measure the effect of a specific treatment and that correlates with the real clinical end-point of fragility fracture.

For more than 20 years, serum type I collagen N-propeptide and crosslinked C-terminal telopeptide were used as markers of bone formation and bone resorption, respectively. However, these markers have several limitations. First, these markers are not bone tissue-specific. Since osteoporosis in elderly patients is often combined with another disease such as that of kidney or liver, the lack of specificity is a crucial issue in clinical use. Sec- ond, these markers cannot reflect the osteocyte activity or peri- osteal apposition that has been recently emphasized in mainte- nance of skeletal integrity. To overcome these limitations, recent studies have focused on the identification of new biological markers. In line with these efforts, in this issue of Endocrinolo- gy and Metabolism, Kim et al. [1] report the potential of plasma macrophage migration inhibitory factor (MIF) as a novel bio- marker of bone metabolism. They demonstrate that higher plas- ma MIF level was inversely correlated with bone mineral densi- ty (BMD) and suggest that it might be a potential early bio- marker of osteoporosis. This is the first clinical study to show

the significant association between circulating MIF level and BMD in postmenopausal women. Although the biological rele- vance or cause-effect relationship between MIF and bone mass was not reported in their study, the authors suggested that estro- gen-withdrawal-related inflammation might be the link between increased MIF and BMD loss [1]. Moreover, tissue resident os- teal macrophages, which play a pivotal role in bone remodeling [2], could be the origin of MIF in high bone turnover status. In this point of view, MIF might be an important player or surro- gate marker in bone remodeling.

Recently, several protein-based biomarkers including perios- tin [3], shingosine-1-phosphate [4], and sclerostin [5] as well as microRNAs [6] have been intensively studied. However, none of the candidates fully satisfied the expected characteristics of (1) bone tissue specificity; (2) stability and celerity of reflecting bone metabolism; and (3) universality to reflect the multiple components of bone metabolism such as osteoblast, osteoclast, and osteocyte. MIF has been established as an inflammatory protein exerting various roles in inflammation and immune functions. To use this factor as a biomarker of bone metabolism, careful consideration is needed.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was re- ported.

Corresponding author: Sun Wook Cho

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea

Tel: +82-2-2072-4761, Fax: +82-2-764-2199, E-mail: swchomd@snu.ac.kr

Copyright © 2016 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Com- mons Attribution Non-Commercial License (http://creativecommons.org/

licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribu- tion, and reproduction in any medium, provided the original work is properly cited.

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Biological Markers for Osteoporosis Endocrinol Metab 2016;31:400-401

http://dx.doi.org/10.3803/EnM.2016.31.3.400 pISSN 2093-596X · eISSN 2093-5978

ORCID

Sun Wook Cho http://orcid.org/0000-0002-7394-3830

REFERENCES

1. Kim H, Ahn SH, Shin C, Lee SH, Kim BJ, Koh JM. The as- sociation of higher plasma macrophage migration inhibitory factor levels with lower bone mineral density and higher bone turnover rate in postmenopausal women. Endocrinol Metab (Seoul) 2016;31:454-61.

2. Cho SW, Soki FN, Koh AJ, Eber MR, Entezami P, Park SI, et al. Osteal macrophages support physiologic skeletal re- modeling and anabolic actions of parathyroid hormone in bone. Proc Natl Acad Sci U S A 2014;111:1545-50.

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Garnero P. Serum periostin is associated with fracture risk in postmenopausal women: a 7-year prospective analysis of the OFELY study. J Clin Endocrinol Metab 2014;99:2533-9.

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Higher circulating sphingosine 1-phosphate levels are asso- ciated with lower bone mineral density and higher bone re- sorption marker in humans. J Clin Endocrinol Metab 2012;

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