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IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women

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Abstract

To find out which of the following parameters—serum levels of insulin-like growth factor 1 (IGF-1), osteoprotegerin (OPG), leptin, osteocalcin (OC), and urinary excretion of N-terminal telopeptide of type I collagen (NTx), can be used as an early marker for osteopenia/osteoporosis in women diagnosed by dual-energy X-ray absorptiometry (DXA), 282 premenopausal and 222 postmenopausal women aged 20–75 years were investigated by the measurement of bone mineral densities (BMDs) at lumbar spine (LS) and femoral neck (FN) by DXA, together with serum concentrations of IGF-1, OPG, leptin, OC, and urinary NTx. The characteristics of the earliest marker(s) were tested with the receiver operating characteristic (ROC) analysis. The area under the curve (AUC), sensitivity, and specificity parameters were determined. It was revealed that serum levels of IGF-1 and leptin changed the earliest, with both markers significantly decreasing (P < 0.0001) or increasing (P = 0.020), respectively, at age 30. However, in ROC analysis, IGF-1 was the only early parameter that had the capacity to differentiate the low bone mass/osteoporosis women from the normal ones (P < 0.0001). If the serum level of IGF-1 at 1.5 SD below its peak was adopted as a cutoff point, it could identify women with low bone mass/osteoporosis with a sensitivity of 73% and specificity of 67%. In the premenopausal women subgroup analysis, the low bone mass women (30/282, 10.6%) were older (38.2 ± 1.7 vs. 34.5 ± 0.5 years; P = 0.026), with lower serum levels of IGF-1 (215.1 ± 22.4 vs. 278.8 ± 9.4 ng/ml; P = 0.02) and less lean mass (33.1 ± 0.6 vs. 34.8 ± 0.2 kg; P = 0.010) than the normal ones. After controlling for age, the serum level of IGF-1 had a weak, but still significant, positive correlation with lean mass (r = 0.17, P < 0.001). In conclusion, measurement of serum IGF-1 in young women may help in the early identification of those at risk for developing low bone mass and osteoporosis.

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References

  1. Kung AW, Ho AY, Ross PD, Reginster JY (2005) Development of a clinical assessment tool in identifying Asian men with low bone mineral density and comparison of its usefulness to quantitative bone ultrasound. Osteoporos Int 16:849–855

    Article  PubMed  Google Scholar 

  2. Ongphiphadhanakul B, Chanprasertyothin S, Payattikul P, Saetung S, Rajatanavin R (2003) The implication of assessing a polymorphism in estrogen receptor alpha gene in the risk assessment of osteoporosis using a screening tool for osteoporosis in Asians. Osteoporos Int 14:863–867

    Article  PubMed  CAS  Google Scholar 

  3. Probst-Hensch NM, Wang H, Goh VH, Seow A, Lee HP, Yu MC (2003) Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women. Cancer Epidemiol Biomarkers Prev 12:739–746

    PubMed  CAS  Google Scholar 

  4. Ruhl CE, Everhart JE (2002) Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res 17:1896–1903

    Article  PubMed  CAS  Google Scholar 

  5. Kudlacek S, Schneider B, Woloszczuk W, Pietschmann P, Willvonseder R, Austrian Study Group on Normative Value of Bone Metabolism (2003) Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone (NY) 32:681–686

    CAS  Google Scholar 

  6. Riggs BL, Khosla S, Melton LJ (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23:279–302

    Article  PubMed  CAS  Google Scholar 

  7. Liu JM, Zhao HY, Ning G, Zhao YJ, Zhang LZ, Sun LH, Xu MY, Chen JL (2004) The relationship between body composition and bone mineral density in healthy young and premenopausal Chinese women. Osteoporosis Int 153:238–242

    Article  Google Scholar 

  8. Zhao HY, Liu JM, Ning G, Zhang YJ, Zhang LZ, Sun LH, Xu MY, Uitterlinden AG, Chen JL (2005) The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women. Osteoporos Int 16:1519–1524

    Article  PubMed  CAS  Google Scholar 

  9. WHO Scientific Group Research on the menopause in the 1990’s (1996) A report of the WHO Scientific Group, vol 866. World Health Organization, Geneva, Switzerland, pp 1–79

    Google Scholar 

  10. WHO (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. WHO Technical Report Series no. 843. WHO, Geneva

    Google Scholar 

  11. Gordeladze JO, Drevon CA, Syversen U, Reseland JE (2002) Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem 85:825–836

    Article  PubMed  CAS  Google Scholar 

  12. Zhao HY, Liu JM, Ning G (2004) Study of relationship between serum leptin level and bone mineral density in postmenopausal women. Shanghai Med 27:4–7

    CAS  Google Scholar 

  13. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, Nicholson GC (2001) Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab 86:1884–1887

    Article  PubMed  CAS  Google Scholar 

  14. Yamauchi M, Sugimoto T, Yamaguchi T, Nakaoka D, Kanzawa M, Yano S, Ozuru R, Suqishita T, Chihara K (2001) Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol 55:341–347

    Article  CAS  Google Scholar 

  15. Zhong N, Wu XP, Xu ZR, Wang AH, Luo XH, Cao XZ, Xie H, Shan PF, Liao EY (2005) Relationship of serum leptin with age, body weight, body mass index, and bone mineral density in healthy mainland Chinese women. Clin Chim Acta 351:161–168

    Article  PubMed  CAS  Google Scholar 

  16. Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240:1285–1293

    Article  PubMed  CAS  Google Scholar 

  17. Dennison EM, Syddall HE, Fall CH, Javaid MK, Arden NK, Phillips DI, Cooper C (2004) Plasma leptin concentration and change in bone density among elderly men and women: the Hertfordshire cohort study. Calcif Tissue Int 74:401–406

    Article  PubMed  CAS  Google Scholar 

  18. Kanbur NO, Derman O, Kmik E (2005) The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents. J Bone Miner Metab 23:76–83

    Article  PubMed  CAS  Google Scholar 

  19. Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D (2002) Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 110:771–781

    Article  PubMed  CAS  Google Scholar 

  20. Munoz-Torres M, Mezuita-Raya P, Lopez-Rodriguez F, Torres-Vela E, de Dios Luna J, Escobar-Jimene F (2001) The contribution of IGF-1 to skeletal integrity in postmenopausal women. Clin Endocrinol 55:759–766

    Article  CAS  Google Scholar 

  21. Gernero P, Sornay-Rendu E, Delmas PD (2000) Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet 355:898–899

    Article  Google Scholar 

  22. Kurland E, Rosen CJ, Cosman F, McMahon D, Chan F, Shane E, Lindsay R, Dempster D, Bilezikian JP (1997) Insulin-like growth factor-I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 82:2799–2805

    Article  PubMed  CAS  Google Scholar 

  23. Zhao HY, Liu JM, Ning G, Zhao YJ, Chen Y, Sun LH, Zhang LZ, Xu MY, Chen JL (2007) Relationships between insulin-like growth factor-I (IGF-I) and OPG, RANKL, bone mineral density in healthy Chinese women. Osteoporosis Int (in press)

  24. Jiang J, Lichtler AC, Gronowiez GA, Adams DJ, Clark SH, Rosen CJ, Kream BE (2006) Transgenic mice with osteoblast-targeted insulin-like growth factor-1 show increased bone remodeling. Bone (NY) 39:494–504

    CAS  Google Scholar 

  25. Niu T, Rosen CJ (2005) The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene (Amst) 361:38–56

    CAS  Google Scholar 

  26. Szulc P, Joly-Pharaboz MO, Marchand F, Delmas PD (2004) Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study. Calcif Tissue Int 74:322–329

    Article  PubMed  CAS  Google Scholar 

  27. Rivadeneira F, van Meurs JB, Kant J, Zillikens MC, Stolk L, Beck TJ, Arp P, Schuit SC, Hofman A, Houwing-Duistermaat JJ, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG (2006) Estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor alpha (ESR1) and insulin-like growth factor I (IGF1) variants influence the risk of fracture in postmenopausal women. J Bone Miner Res 21:1443–1456

    Article  PubMed  CAS  Google Scholar 

  28. Vanderschueren D, Gevers G, Raymaekers G, Devos P, Dequeker J (1990) Sex-and age-related changes in bone and serum osteocalcin. Calcif Tissue Int 46:179–182

    Article  PubMed  CAS  Google Scholar 

  29. Resch H, Pietschmann P, Kudlacek S, Woloszczuk W, Krexner E, Bernecher P, Willvonseder R (1994) Influence of sex and age on biochemical bone metabolism parameters. Miner Electrolyte Metab 20:117–121

    PubMed  CAS  Google Scholar 

  30. Ebeling PR, Atley LM, Guthrie JR, Burger HG, Dennerstein L, Hopper JL, Wark JD (1996) Bone turnover markers and bone density across the menopausal transition. J Clin Endocrinol Metab 81:3366–3371

    Article  PubMed  CAS  Google Scholar 

  31. Kakonen SM, Hellman J, Karp M, Laaksoner P, Obrant KJ, Väänänen HK, Lövgren T, Pettersson K (2000) Development and evaluation of three immunofluorometric assays that measure different forms of osteocalcin in serum. Clin Chem 46:332–337

    PubMed  CAS  Google Scholar 

  32. Iki M, Morita A, Ikeda Y, Sato Y, Akiba T, Matsumoto T, Nishino H, Kagamimori H, Kagawa Y, Yoneshima H; JPOS Study Group (2007) Biochemical markers of bone turnover may predict progression to osteoporosis in osteopenic women: the JPOS Cohort Study. J Bone Miner Metab 25:122–129

    Article  PubMed  CAS  Google Scholar 

  33. Pietschmann P, Resch H, Krexner E, Woloszczuk W, Willvonseder R (1991) Decreased serum osteocalcin levels in patients with postmenopausal osteoporosis. Acta Med Aust 18: 114–116

    CAS  Google Scholar 

  34. Akesson K, Ljunghall S, Jonsson B, Sernbo I, Johnell O, Gärdsell P, Obrant KJ (1995) Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: a retrospective and prospective population-based study of women. J Bone Miner Res 10:1823–1829

    Article  PubMed  CAS  Google Scholar 

  35. Desai MP, Bhanuprakash KV, Khatkhatay MI, Donde UM (2007) Age-related changes in bone turnover markers and ovarian hormones in premenopausal and postmenopausal Indian women. J Clin Lab Anal 21:55–60

    Article  PubMed  CAS  Google Scholar 

  36. Ivaska KK, Hentunen TA, Vääräniemi J, Ylipahkala H, Pettersson K, Väänänen HK (2004) Release of intact and fragmented osteocalcin molecules from bone matrix during bone resorption in vitro. J Biol Chem 279:18361–18369

    Article  PubMed  CAS  Google Scholar 

  37. Delmas PD, Eastell R, Garneo P, Seibel MJ, Stepan J; Committee of Scientific Advisors of the International Osteoporosis Foundation (2000) The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 11(suppl 6):S2–S17

    Article  PubMed  Google Scholar 

  38. Berger CE, Kröner A, Thomas E, Kristen KH, Ogris E, Engel A (2002) Comparison of biochemical markers of bone metabolism in serum and femur aspirates. Clin Orthop 395:174–179

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University Medical School, 197 Shanghai Rui-jin Er Road, Shanghai, 200025, China

    Jian-min Liu, Hong-yan Zhao, Guang Ning, Ying Chen, Lian-zhen Zhang, Li-hao Sun, Yong-ju Zhao, Man-yin Xu & Jia-lun Chen

  2. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Endocrine and Metabolic Division, E-Institutes of Shanghai Universities (EISU), Shanghai, China

    Jian-min Liu, Hong-yan Zhao, Guang Ning, Ying Chen, Lian-zhen Zhang, Li-hao Sun, Yong-ju Zhao, Man-yin Xu & Jia-lun Chen

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  1. Jian-min Liu
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  2. Hong-yan Zhao
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  3. Guang Ning
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  9. Jia-lun Chen
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Correspondence to Guang Ning.

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Liu, Jm., Zhao, Hy., Ning, G. et al. IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab 26, 159–164 (2008). https://doi.org/10.1007/s00774-007-0799-z

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  • DOI: https://doi.org/10.1007/s00774-007-0799-z

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