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Erschienen in: Calcified Tissue International 3/2009

01.09.2009

Serum Osteocalcin/Bone-Specific Alkaline Phosphatase Ratio Is a Predictor for the Presence of Vertebral Fractures in Men with Type 2 Diabetes

verfasst von: Ippei Kanazawa, Toru Yamaguchi, Masahiro Yamamoto, Mika Yamauchi, Shozo Yano, Toshitsugu Sugimoto

Erschienen in: Calcified Tissue International | Ausgabe 3/2009

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Abstract

We examined whether or not BMD or bone markers were useful for assessing the risk of vertebral fractures in 248 Japanese men with type 2 diabetes. We analyzed the relationships between bone markers (osteocalcin [OC], bone-specific alkaline phosphatase [BAP], urinary N-terminal cross-linked telopeptide of type-I collagen) or BMD and HbA1c, urinary C-peptide, insulin-like growth factor-I (IGF-I), parathyroid hormone, 1,25(OH)2 vitamin D, and the presence of prevalent vertebral fractures. Multiple regression analysis adjusted for age, body height, weight, duration of diabetes, and serum creatinine showed that serum OC and OC/BAP ratio were correlated negatively with HbA1c (P < 0.01) and positively with IGF-I (P < 0.01). Multivariate logistic regression analysis adjusted for the above parameters showed that serum OC/BAP ratio was inversely associated with the presence of vertebral fractures (odds ratio = 0.695, P < 0.05). This association was still significant after additional adjustment for lumbar or femoral neck BMD. Our results suggest that poor diabetic control and lower IGF-I level are linked to impaired bone formation and resultant reduction in OC/BAP ratio in men with type 2 diabetes. The OC/BAP ratio could be clinically useful for assessing the risk of vertebral fractures independent of BMD in diabetic men.
Literatur
1.
Zurück zum Zitat Barrett-Connor E, Holbrook TL (1992) Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 268:3333–3337PubMedCrossRef Barrett-Connor E, Holbrook TL (1992) Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 268:3333–3337PubMedCrossRef
2.
Zurück zum Zitat Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–882PubMedCrossRef Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–882PubMedCrossRef
3.
Zurück zum Zitat Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11:556–561PubMedCrossRef Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11:556–561PubMedCrossRef
4.
Zurück zum Zitat Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRef Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRef
5.
Zurück zum Zitat Lipscombe LL, Jamal SA, Booth GL, Hawker GA (2007) The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care 30:835–841PubMedCrossRef Lipscombe LL, Jamal SA, Booth GL, Hawker GA (2007) The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care 30:835–841PubMedCrossRef
6.
Zurück zum Zitat Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2005) Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 165:1612–1617PubMedCrossRef Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, Tylavsky FA, de Rekeneire N, Harris TB, Newman AB (2005) Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med 165:1612–1617PubMedCrossRef
7.
Zurück zum Zitat Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of bone mineral density or diabetic complications. J Bone Miner Res 24:702–709PubMedCrossRef Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of bone mineral density or diabetic complications. J Bone Miner Res 24:702–709PubMedCrossRef
8.
Zurück zum Zitat Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 17:1514–1523PubMedCrossRef Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 17:1514–1523PubMedCrossRef
9.
Zurück zum Zitat Terada M, Inaba M, Yano Y, Hasuma T, Nishizawa Y, Morii H, Otani S (1998) Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells. Bone 22:17–23PubMedCrossRef Terada M, Inaba M, Yano Y, Hasuma T, Nishizawa Y, Morii H, Otani S (1998) Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells. Bone 22:17–23PubMedCrossRef
10.
Zurück zum Zitat Botolin S, MacCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99:411–424PubMedCrossRef Botolin S, MacCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99:411–424PubMedCrossRef
11.
Zurück zum Zitat Gopalakrishnan V, Vignesh RC, Arunakaran J, Aruldhas MM, Srinivasan N (2006) Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages. Biochem Cell Biol 84:93–101PubMedCrossRef Gopalakrishnan V, Vignesh RC, Arunakaran J, Aruldhas MM, Srinivasan N (2006) Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages. Biochem Cell Biol 84:93–101PubMedCrossRef
12.
Zurück zum Zitat Verhaeghe J, Suiker AM, Nyomba BL, Visser WJ, Einhorn TA, Dequeker J, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology 124:573–582PubMedCrossRef Verhaeghe J, Suiker AM, Nyomba BL, Visser WJ, Einhorn TA, Dequeker J, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology 124:573–582PubMedCrossRef
13.
Zurück zum Zitat Gerdhem P, Isaksson A, Akesson K, Obrant KJ (2005) Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int 16:1506–1512PubMedCrossRef Gerdhem P, Isaksson A, Akesson K, Obrant KJ (2005) Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int 16:1506–1512PubMedCrossRef
14.
Zurück zum Zitat Li YM, Schilling T, Benisch P, Zeck S, Meissner-Weigl J, Schneider D, Limbert C, Seufert J, Kassem M, Schutze N, Jakob F, Ebert R (2007) Effects of high glucose on mesenchymal stem cell proliferation and differentiation. Biochem Biophys Res Commun 363:209–215PubMedCrossRef Li YM, Schilling T, Benisch P, Zeck S, Meissner-Weigl J, Schneider D, Limbert C, Seufert J, Kassem M, Schutze N, Jakob F, Ebert R (2007) Effects of high glucose on mesenchymal stem cell proliferation and differentiation. Biochem Biophys Res Commun 363:209–215PubMedCrossRef
15.
Zurück zum Zitat Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, Pischon N, Trackman PC, Gerstenfeld L, Graves DT (2007) Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 40:345–353PubMedCrossRef Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, Pischon N, Trackman PC, Gerstenfeld L, Graves DT (2007) Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 40:345–353PubMedCrossRef
16.
Zurück zum Zitat Brenner RE, Riemenschneider B, Blum W, Morike M, Teller WM, Pirsig W, Heinze E (1992) Defective stimulation of proliferation and collagen biosynthesis of human bone cells by serum from diabetic patients. Acta Endocrinol 127:509–514PubMed Brenner RE, Riemenschneider B, Blum W, Morike M, Teller WM, Pirsig W, Heinze E (1992) Defective stimulation of proliferation and collagen biosynthesis of human bone cells by serum from diabetic patients. Acta Endocrinol 127:509–514PubMed
17.
Zurück zum Zitat Balint E, Szabo P, Marshall CF, Sprague SM (2001) Glucose-induced inhibition of in vitro bone mineralization. Bone 28:21–28PubMedCrossRef Balint E, Szabo P, Marshall CF, Sprague SM (2001) Glucose-induced inhibition of in vitro bone mineralization. Bone 28:21–28PubMedCrossRef
18.
Zurück zum Zitat Yamamoto T, Ozono K, Miyauchi A, Kasayama S, Kojima Y, Shima M, Okada S (2001) Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. Am J Kidney Dis 38:S161–S164PubMedCrossRef Yamamoto T, Ozono K, Miyauchi A, Kasayama S, Kojima Y, Shima M, Okada S (2001) Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy. Am J Kidney Dis 38:S161–S164PubMedCrossRef
19.
Zurück zum Zitat Ogawa N, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs. Horm Metab Res 39:871–875PubMedCrossRef Ogawa N, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs. Horm Metab Res 39:871–875PubMedCrossRef
20.
Zurück zum Zitat Okazaki R, Totsuka Y, Hamano K, Ajima M, Miura M, Hirota Y, Hata K, Fukumoto S, Matsumoto T (1997) Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 82:2915–2920PubMedCrossRef Okazaki R, Totsuka Y, Hamano K, Ajima M, Miura M, Hirota Y, Hata K, Fukumoto S, Matsumoto T (1997) Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 82:2915–2920PubMedCrossRef
21.
Zurück zum Zitat Stein GS, Lian JB (1993) Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev 14:424–442PubMed Stein GS, Lian JB (1993) Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev 14:424–442PubMed
22.
Zurück zum Zitat Reid IR, Evans MC, Cooper GJ, Ames RW, Stapleton J (1993) Circulating insulin levels are related to bone density in normal postmenopausal women. Am J Physiol Endocrinol Metab 265:E655–E659 Reid IR, Evans MC, Cooper GJ, Ames RW, Stapleton J (1993) Circulating insulin levels are related to bone density in normal postmenopausal women. Am J Physiol Endocrinol Metab 265:E655–E659
23.
Zurück zum Zitat Abrahamsen B, Rohold A, Henriksen JE, Beck-Nielsen H (2000) Correlations between insulin sensitivity and bone mineral density in non-diabetic men. Diabet Med 17:124–129PubMedCrossRef Abrahamsen B, Rohold A, Henriksen JE, Beck-Nielsen H (2000) Correlations between insulin sensitivity and bone mineral density in non-diabetic men. Diabet Med 17:124–129PubMedCrossRef
24.
Zurück zum Zitat Ravn P, Cizza G, Bjarnason NH, Thompson D, Daley M, Wasnich RD, McClung M, Hosking D, Yates AJ, Christiansen C (1999) Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group. J Bone Miner Res 14:1622–1627PubMedCrossRef Ravn P, Cizza G, Bjarnason NH, Thompson D, Daley M, Wasnich RD, McClung M, Hosking D, Yates AJ, Christiansen C (1999) Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group. J Bone Miner Res 14:1622–1627PubMedCrossRef
25.
Zurück zum Zitat Sugimoto T, Ritter C, Morrissey J, Hayes C, Slatopolsky E (1990) Effects of high concentrations of glucose on PTH secretion in parathyroid cells. Kidney Int 37:1522–1527PubMedCrossRef Sugimoto T, Ritter C, Morrissey J, Hayes C, Slatopolsky E (1990) Effects of high concentrations of glucose on PTH secretion in parathyroid cells. Kidney Int 37:1522–1527PubMedCrossRef
26.
Zurück zum Zitat Hanaire-Broutin H, Sallerin-Caute B, Poncet MF, Tauber M, Bastide R, Rosenfeld R, Tauber JP (1996) Insulin therapy and GH-IGF-I axis disorders in diabetes: impact of glycemic control and hepatic insulization. Diabetes Metab 22:245–250PubMed Hanaire-Broutin H, Sallerin-Caute B, Poncet MF, Tauber M, Bastide R, Rosenfeld R, Tauber JP (1996) Insulin therapy and GH-IGF-I axis disorders in diabetes: impact of glycemic control and hepatic insulization. Diabetes Metab 22:245–250PubMed
27.
28.
Zurück zum Zitat Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–996PubMedCrossRef Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–996PubMedCrossRef
29.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2007) Serum insulin-like growth factor-I is associated with the presence of vertebral fractures in postmonopausal women with type 2 diabetes mellitus. Osteoporos Int 18:1675–1681PubMedCrossRef Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2007) Serum insulin-like growth factor-I is associated with the presence of vertebral fractures in postmonopausal women with type 2 diabetes mellitus. Osteoporos Int 18:1675–1681PubMedCrossRef
30.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2008) Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. Calcif Tissue Int 83:324–331PubMedCrossRef Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2008) Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. Calcif Tissue Int 83:324–331PubMedCrossRef
31.
Zurück zum Zitat Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2007) Bone mineral density is not sensitive enough to assess the risk of vertebral fractures in type 2 diabetic women. Calcif Tissue Int 80:353–358PubMedCrossRef Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2007) Bone mineral density is not sensitive enough to assess the risk of vertebral fractures in type 2 diabetic women. Calcif Tissue Int 80:353–358PubMedCrossRef
32.
Zurück zum Zitat Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019PubMedCrossRef Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019PubMedCrossRef
33.
Zurück zum Zitat Thrailkill KM (2000) Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility. Diabetes Technol Ther 2:69–80PubMedCrossRef Thrailkill KM (2000) Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility. Diabetes Technol Ther 2:69–80PubMedCrossRef
34.
Zurück zum Zitat McCarthy TL, Centrella M, Canalis E (1989) Insulin-like growth factor (IGF) and bone. Connect Tissue Res 20:277–282PubMedCrossRef McCarthy TL, Centrella M, Canalis E (1989) Insulin-like growth factor (IGF) and bone. Connect Tissue Res 20:277–282PubMedCrossRef
35.
Zurück zum Zitat Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K (1997) Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 12:1272–1279PubMedCrossRef Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K (1997) Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 12:1272–1279PubMedCrossRef
36.
Zurück zum Zitat Yamaguchi T, Kanatani M, Yamauchi M, Kaji H, Sugishita T, Baylink DJ, Mohan S, Chihara K, Sugimoto T (2006) Serum levels of insulin-like growth factor (IGF); IGF-binding protein-3, -4, and -5; and their relationships to bone mineral density and the risk of vertebral fractures in postmenopausal women. Calcif Tissue Int 78:18–24PubMedCrossRef Yamaguchi T, Kanatani M, Yamauchi M, Kaji H, Sugishita T, Baylink DJ, Mohan S, Chihara K, Sugimoto T (2006) Serum levels of insulin-like growth factor (IGF); IGF-binding protein-3, -4, and -5; and their relationships to bone mineral density and the risk of vertebral fractures in postmenopausal women. Calcif Tissue Int 78:18–24PubMedCrossRef
37.
Zurück zum Zitat Raskin P, Stevenson MR, Barilla DE, Pak CY (1978) The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol 9:329–335CrossRef Raskin P, Stevenson MR, Barilla DE, Pak CY (1978) The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol 9:329–335CrossRef
38.
Zurück zum Zitat Kawagishi T, Morii H, Nakatsuka K, Sasao K, Kawasaki K, Miki T, Nishizawa Y (1991) Parathyroid hormone secretion in diabetes mellitus. Contrib Nephrol 90:217–222PubMed Kawagishi T, Morii H, Nakatsuka K, Sasao K, Kawasaki K, Miki T, Nishizawa Y (1991) Parathyroid hormone secretion in diabetes mellitus. Contrib Nephrol 90:217–222PubMed
39.
40.
Zurück zum Zitat Fujimoto WY (1996) Overview of non-insulin-dependent diabetes mellitus (NIDDM) in different population groups. Diabet Med 13:S7–S10PubMedCrossRef Fujimoto WY (1996) Overview of non-insulin-dependent diabetes mellitus (NIDDM) in different population groups. Diabet Med 13:S7–S10PubMedCrossRef
41.
Zurück zum Zitat Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469PubMedCrossRef Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469PubMedCrossRef
42.
Zurück zum Zitat Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270PubMedCrossRef Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270PubMedCrossRef
Metadaten
Titel
Serum Osteocalcin/Bone-Specific Alkaline Phosphatase Ratio Is a Predictor for the Presence of Vertebral Fractures in Men with Type 2 Diabetes
verfasst von
Ippei Kanazawa
Toru Yamaguchi
Masahiro Yamamoto
Mika Yamauchi
Shozo Yano
Toshitsugu Sugimoto
Publikationsdatum
01.09.2009
Verlag
Springer-Verlag
Erschienen in
Calcified Tissue International / Ausgabe 3/2009
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-009-9272-4

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