J Bone Metab.  2013 May;20(1):37-41. 10.11005/jbm.2013.20.1.37.

Changes in Serum Osteocalcin are Not Associated with Changes in Glucose or Insulin for Osteoporotic Patients Treated with Bisphosphonate

• Hong SH
• Koo JW
• Hwang JK
• Hwang YC
• Jeong IK
• Ahn KJ
• Chung HY
• Kim DY

• KMID: 2286311
• DOI: http://doi.org/10.11005/jbm.2013.20.1.37

Abstract

BACKGROUND
Bisphosphonate is used in osteoporosis treatment to repress osteoclast activity, which then decreases levels of osteocalcin (OC). OC, a protein secreted by osteoblasts and released from the bone matrix during osteoclastic bone resorption, has been found to control blood glucose levels by increasing insulin production and sensitivity. The question addressed in this study is whether decreasing OC through bisphosphonate treatment will provoke a change in glucose homeostasis.
METHODS
Eighty-four patients with osteoporosis were treated with once-weekly risedronate 35 mg and cholecalciferol 5,600 IU. We measured fasting plasma glucose (FPG), insulin, and undercarboxylated (Glu) and carboxylated (Gla) OC levels at baseline and after 16 weeks. To estimate insulin resistance (IR) and beta-cell function (B)%, homeostasis model assessment (HOMA)-IR and HOMA-B% were also calculated, respectively.
RESULTS
The mean FPG level in total subjects increased significantly from 5.3 to 5.5 mmol/L, but no changes in blood glucose were noted in the 24 subjects with impaired fasting glucose. Glu and Gla OC levels declined significantly after treatment. No correlations were observed between changes in OC and changes in glucose, however.
CONCLUSIONS
Bisphosphonate treatment for osteoporosis reduced OC, but this change was not associated with changes in glucose metabolism.

Keyword

Bisphosphonate; Glucose; Osteocalcin

MeSH Terms

Blood Glucose
Bone Matrix
Bone Resorption
Cholecalciferol
Etidronic Acid
Fasting
Glucose
Homeostasis
Humans
Insulin
Insulin Resistance
Osteoblasts
Osteocalcin
Osteoclasts
Osteoporosis
Plasma
Risedronate Sodium
Blood Glucose
Cholecalciferol
Etidronic Acid
Glucose
Insulin
Osteocalcin

Reference

1. Motyl KJ, McCabe LR, Schwartz AV. Bone and glucose meta bolism: a two-way street. Arch Biochem Biophys. 2010. 503:2–10.

2. Ferron M, Wei J, Yoshizawa T, et al. An ELISA-based method to quantify osteocalcin carboxylation in mice. Biochem Biophys Res Commun. 2010. 397:691–696.

3. Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007. 130:456–469.

4. Ferron M, Hinoi E, Karsenty G, et al. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A. 2008. 105:5266–5270.

5. Fernández-Real JM, Izquierdo M, Ortega F, et al. The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab. 2009. 94:237–245.

6. Im JA, Yu BP, Jeon JY, et al. Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta. 2008. 396:66–69.

7. Kindblom JM, Ohlsson C, Ljunggren O, et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res. 2009. 24:785–791.

8. Liberman UA, Weiss SR, Bröll J, et al. The Alendronate Phase III Osteoporosis Treatment Study Group. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med. 1995. 333:1437–1443.

9. Chung HY, Chin SO, Kang MI, et al. Efficacy of risedronate with cholecalciferol on 25-hydroxyvitamin D level and bone turnover in Korean patients with osteoporosis. Clin Endocrinol (Oxf). 2011. 74:699–704.

10. Kanazawa I, Yamaguchi T, Yamamoto M, et al. Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009. 94:45–49.

11. Yeap BB, Chubb SA, Flicker L, et al. Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol. 2010. 163:265–272.

12. Hwang YC, Jeong IK, Ahn KJ, et al. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diabetes Metab Res Rev. 2009. 25:768–772.

13. Iki M, Tamaki J, Fujita Y, et al. Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study. Osteoporos Int. 2012. 23:761–770.

14. Shea MK, Gundberg CM, Meigs JB, et al. Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr. 2009. 90:1230–1235.

15. Schwartz AV, Schafer AL, Grey A, et al. Effects of antiresorptive therapies on glucose metabolism: Results from the FIT, HORIZON-PFT and FREEDOM trials. J Bone Miner Res. 2013. doi: http://dx.doi.org/10.1002/jbmr.1865.

16. Vestergaard P. Risk of newly diagnosed type 2 diabetes is reduced in users of alendronate. Calcif Tissue Int. 2011. 89:265–270.

17. Dane C, Dane B, Cetin A, et al. Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis. Gynecol Endocrinol. 2007. 23:398–403.

18. Kanaya AM, Herrington D, Vittinghoff E, et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003. 138:1–9.

19. Margolis KL, Bonds DE, Rodabough RJ, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Womens Health Initiative Hormone Trial. Diabetologia. 2004. 47:1175–1187.

20. Hwang YC, Jee JH, Jeong IK, et al. Circulating osteocalcin level is not associated with incident type 2 diabetes in middle-aged male subjects: mean 8.4-year retrospective follow-up study. Diabetes Care. 2012. 35:1919–1924.