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Published in: Osteoporosis International 9/2008

01-09-2008 | Original Article

Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogs

Authors: M. Saito, S. Mori, T. Mashiba, S. Komatsubara, K. Marumo

Published in: Osteoporosis International | Issue 9/2008

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Abstract

Summary

Collagen cross-linking is a determinant of bone quality. A three-year treatment of bisphosphonate—incadronate disodium—in beagles increased degree of mineralization, collagen maturity, and pentosidine, a compound with advanced glycation end products. The treatment had no effect on the total amount of enzymatic cross-link formation.

Introduction

Collagen cross-linking is a determinant of bone quality. Recently, we reported that long-term treatment with bisphosphonate increased microdamage accumulation. The aim of this study was to clarify the effect of a three-year treatment with bisphosphonate on degree of mineralization and immature and mature enzymatic cross-links and non-enzymatic collagen cross-link, pentosidine, in cortical bone in the same dogs.

Methods

Twenty-nine 1-year-old beagles (15 males, 14 females) were divided into three groups that daily were given vehicle or incadronate at doses of 0.3 or 0.6 mg/kg/day orally for three years. A cortex of a rib was fractionated into low- and high-density portions. The contents of calcium, phosphorus, enzymatic immature and mature cross-links, and the non-enzymatic glycation product pentosidine were determined in each fraction.

Results

Calcium, phosphorus, and pentosidine contents and the ratio of mature to immature cross-links increased significantly with incadronate in a dose-dependent manner, but the total amount of enzymatic cross-links was unchanged. The pentosidine content correlated inversely with cortical activation frequency (p < 0.01).

Conclusion

Long-term suppression of bone remodeling by bisphosphonate increases degree of mineralization, collagen maturity, and non-enzymatic cross-linking.
Literature
1.
go back to reference Burr DB (2002) Bone material properties and mineral matrix contributions to fracture risk or age in women and men. J Musculoskelet Neuronal Interact 2:201–204PubMed Burr DB (2002) Bone material properties and mineral matrix contributions to fracture risk or age in women and men. J Musculoskelet Neuronal Interact 2:201–204PubMed
2.
go back to reference Turner CH (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteopor Int 13:97–104CrossRef Turner CH (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteopor Int 13:97–104CrossRef
3.
go back to reference Boivin GY, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteopor Int 14(supple 3):S19–S24 Boivin GY, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteopor Int 14(supple 3):S19–S24
4.
go back to reference Mori S, Harruff R, Ammrosius W et al (1997) Trabecular bone volume and microdamage accumulation on the femoral heads of women with and without femoral neck fractures. Bone 21:521–526PubMedCrossRef Mori S, Harruff R, Ammrosius W et al (1997) Trabecular bone volume and microdamage accumulation on the femoral heads of women with and without femoral neck fractures. Bone 21:521–526PubMedCrossRef
5.
go back to reference Vashishth D (2007) The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep 5:62–66PubMed Vashishth D (2007) The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep 5:62–66PubMed
6.
go back to reference Komatsubara S, Mori S, Mashiba T et al (2003) Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res 18:512–520PubMedCrossRef Komatsubara S, Mori S, Mashiba T et al (2003) Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res 18:512–520PubMedCrossRef
7.
go back to reference Komatsubara S, Mori S, Mashiba T et al (2004) Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res 19:999–1005PubMedCrossRef Komatsubara S, Mori S, Mashiba T et al (2004) Suppressed bone turnover by long-term bisphosphonate treatment accumulates microdamage but maintains intrinsic material properties in cortical bone of dog rib. J Bone Miner Res 19:999–1005PubMedCrossRef
8.
go back to reference Oxlund H, Barckman M, Ortoft G et al (1995) Reduced concentrations of collagen cross-links are associated with reduced strength of bone. Bone 17:365S–371SPubMed Oxlund H, Barckman M, Ortoft G et al (1995) Reduced concentrations of collagen cross-links are associated with reduced strength of bone. Bone 17:365S–371SPubMed
9.
go back to reference Wang X, Shen X, Li X et al (2002) Age-related changes in the collagen network and toughness of bone. Bone 31:1–7PubMedCrossRef Wang X, Shen X, Li X et al (2002) Age-related changes in the collagen network and toughness of bone. Bone 31:1–7PubMedCrossRef
10.
go back to reference Tang SY, Zeenath U, Vashishth D (2007) Effects of non-enzymatic glycation on cancellous bone fragility. Bone 40:1144–1151PubMedCrossRef Tang SY, Zeenath U, Vashishth D (2007) Effects of non-enzymatic glycation on cancellous bone fragility. Bone 40:1144–1151PubMedCrossRef
11.
go back to reference Saito M, Fujii K, Mori Y et al (2006) 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 et al (2006) 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
12.
go back to reference Kuboki Y, Kudo A, Mizuno M et al (1992) Time-dependent changes of collagen cross-links and their precursors in the culture of osteogenic cells. Calcif Tissue Int 50:473–480PubMedCrossRef Kuboki Y, Kudo A, Mizuno M et al (1992) Time-dependent changes of collagen cross-links and their precursors in the culture of osteogenic cells. Calcif Tissue Int 50:473–480PubMedCrossRef
13.
go back to reference Yamauchi M, Katz EP (1993) The post-translational chemistry and molecular packing of mineralizing tendon collagens. Connect Tissue Res 29:81–98PubMedCrossRef Yamauchi M, Katz EP (1993) The post-translational chemistry and molecular packing of mineralizing tendon collagens. Connect Tissue Res 29:81–98PubMedCrossRef
14.
go back to reference Saito M, Soshi S, Fujii K (2003) Effect of hyper- and microgravity on collagen post-translatonal controls of MC3T3-E1 osteoblasts. J Bone Miner Res 18:1695–1705PubMedCrossRef Saito M, Soshi S, Fujii K (2003) Effect of hyper- and microgravity on collagen post-translatonal controls of MC3T3-E1 osteoblasts. J Bone Miner Res 18:1695–1705PubMedCrossRef
15.
go back to reference Saito M, Sohsi S, Tanaka T et al (2004) Intensity-related differences in collagen post-traslational modification in MC3T3-E1 osteoblasts after exposure to low and high intensity pulsed ultrasound. Bone 35:644–655PubMedCrossRef Saito M, Sohsi S, Tanaka T et al (2004) Intensity-related differences in collagen post-traslational modification in MC3T3-E1 osteoblasts after exposure to low and high intensity pulsed ultrasound. Bone 35:644–655PubMedCrossRef
16.
go back to reference Saito M, Fujii K, Tanaka T et al (2004) Effect of low- and high-intensity pulsed ultrasound on collagen post-translational modifications in MC3T3-E1 osteoblasts. Calcif Tissue Int 75:384–395PubMedCrossRef Saito M, Fujii K, Tanaka T et al (2004) Effect of low- and high-intensity pulsed ultrasound on collagen post-translational modifications in MC3T3-E1 osteoblasts. Calcif Tissue Int 75:384–395PubMedCrossRef
17.
go back to reference Paschalis EP, Recker R, Dicarlo E et al (2003) Distribution of collagen cross-links in normal human trabecular bone. J Bone Miner Res 18:1942–1946PubMedCrossRef Paschalis EP, Recker R, Dicarlo E et al (2003) Distribution of collagen cross-links in normal human trabecular bone. J Bone Miner Res 18:1942–1946PubMedCrossRef
18.
go back to reference Uzawa K, Grzesik WJ, Nishiura T et al (1999) Differential expression of human lysyl hydroxylase genes, lysyl hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro. J Bone Miner Res 14:1272–1280PubMedCrossRef Uzawa K, Grzesik WJ, Nishiura T et al (1999) Differential expression of human lysyl hydroxylase genes, lysyl hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro. J Bone Miner Res 14:1272–1280PubMedCrossRef
19.
go back to reference Banse X, Sims TJ, Bailey AJ (2002) Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links. J Bone Miner Res 17:1621–1628PubMedCrossRef Banse X, Sims TJ, Bailey AJ (2002) Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links. J Bone Miner Res 17:1621–1628PubMedCrossRef
20.
go back to reference Oxlund H, Mosekilde L, Ortoft G (1996) Reduced concentration of collagen reducible crosslinks in human trabecular bone with respect to age and osteoporosis. Bone 19:479–484PubMedCrossRef Oxlund H, Mosekilde L, Ortoft G (1996) Reduced concentration of collagen reducible crosslinks in human trabecular bone with respect to age and osteoporosis. Bone 19:479–484PubMedCrossRef
21.
go back to reference Eyre DR, Dickson IR, Ness KV (1988) Collagen cross-linking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues. Biochem J 252:495–500PubMed Eyre DR, Dickson IR, Ness KV (1988) Collagen cross-linking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues. Biochem J 252:495–500PubMed
22.
go back to reference Marumo K, Saito M, Yamagishi M et al (2005) The “ligamentization” process in human anterior cruciate ligament reconstruction with autogenous patellar and hamstring tendons. Am J Sports Med 33:1166–1173PubMedCrossRef Marumo K, Saito M, Yamagishi M et al (2005) The “ligamentization” process in human anterior cruciate ligament reconstruction with autogenous patellar and hamstring tendons. Am J Sports Med 33:1166–1173PubMedCrossRef
23.
go back to reference Saito M, Marumo K, Fujii K et al (1997) Single column high – performance liquid chromatographic - fluorescence detection of immature, mature and senescent cross-links of collagen. Anal Biochem 253:26–32PubMedCrossRef Saito M, Marumo K, Fujii K et al (1997) Single column high – performance liquid chromatographic - fluorescence detection of immature, mature and senescent cross-links of collagen. Anal Biochem 253:26–32PubMedCrossRef
24.
go back to reference Vashishth D, Gibson GJ, Khoury JI et al (2001) Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 28:195–201PubMedCrossRef Vashishth D, Gibson GJ, Khoury JI et al (2001) Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 28:195–201PubMedCrossRef
25.
go back to reference McCarthy AD, Etcheverry SB, Bruzzone L et al (2001) Non-enzymatic glycation of a type I collagen matrix: effect on osteoblastic development and oxidative stress. BMC Cell Biol 2:16PubMedCrossRef McCarthy AD, Etcheverry SB, Bruzzone L et al (2001) Non-enzymatic glycation of a type I collagen matrix: effect on osteoblastic development and oxidative stress. BMC Cell Biol 2:16PubMedCrossRef
26.
go back to reference Paul RG, Bailey AJ (1996) Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol 28:1297–310PubMedCrossRef Paul RG, Bailey AJ (1996) Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol 28:1297–310PubMedCrossRef
27.
go back to reference Sell DR, Monnier VM (1989) Structure elucidation of a senescence cross-link from human extracellular matrix, Implication of pentoses in the aging process. J Biol Chem 264:21597–21602PubMed Sell DR, Monnier VM (1989) Structure elucidation of a senescence cross-link from human extracellular matrix, Implication of pentoses in the aging process. J Biol Chem 264:21597–21602PubMed
28.
go back to reference Saito M (1999) Age-related changes in biochemical characteristics of collagen from human weight-bearing and non-weight-bearing bone. Tokyo Jikeikai Medical Journal 114:327–337 (in Japanese) Saito M (1999) Age-related changes in biochemical characteristics of collagen from human weight-bearing and non-weight-bearing bone. Tokyo Jikeikai Medical Journal 114:327–337 (in Japanese)
29.
go back to reference Saito M, Fujii K, Soshi S et al (2006) Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation induced pentosidine in the femoral neck cortex in cases of femoral neck fracture. Osteoporos Int 17:986–995PubMedCrossRef Saito M, Fujii K, Soshi S et al (2006) Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation induced pentosidine in the femoral neck cortex in cases of femoral neck fracture. Osteoporos Int 17:986–995PubMedCrossRef
30.
go back to reference Saito M, Fujii K, Marumo K (2006) Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 79:160–168PubMedCrossRef Saito M, Fujii K, Marumo K (2006) Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 79:160–168PubMedCrossRef
31.
go back to reference Garnero P, Borel O, Gineyts E et al (2006) Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 38:300–309PubMedCrossRef Garnero P, Borel O, Gineyts E et al (2006) Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 38:300–309PubMedCrossRef
32.
go back to reference Allen MR, Iwata K, Phipps R, Burr DB (2006) Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone 39:872–879PubMedCrossRef Allen MR, Iwata K, Phipps R, Burr DB (2006) Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone 39:872–879PubMedCrossRef
33.
go back to reference Jowsey J (1964) Variation in bone mineralization with age and disease. In: Bone biodynamics. Little Brown, Boston, pp 461–479 Jowsey J (1964) Variation in bone mineralization with age and disease. In: Bone biodynamics. Little Brown, Boston, pp 461–479
34.
go back to reference Boivin GY, Chavassieux PM, Santora AC et al (2000) Alendronate increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694PubMedCrossRef Boivin GY, Chavassieux PM, Santora AC et al (2000) Alendronate increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694PubMedCrossRef
35.
go back to reference Grynpas M, Marie PJ (1990) Effects of low-doses of strontium on bone quality and quantity in rats. Bone 11:313–319PubMedCrossRef Grynpas M, Marie PJ (1990) Effects of low-doses of strontium on bone quality and quantity in rats. Bone 11:313–319PubMedCrossRef
36.
go back to reference Sodek KL, Tupy JH, Sodek J et al (2000) Relationships between bone protein and mineral in developing porcine bone and calvaria. Bone 26:189–198PubMedCrossRef Sodek KL, Tupy JH, Sodek J et al (2000) Relationships between bone protein and mineral in developing porcine bone and calvaria. Bone 26:189–198PubMedCrossRef
37.
go back to reference Vukicevic S, Stavljenic A, Boll T et al (1989) Effects of parathyroidectomy on tissue calcium, phosphorus, magnesium, and copper concentrations in aluminum-loaded uremic rats. Biol Trace Elem Res 22:45–53PubMedCrossRef Vukicevic S, Stavljenic A, Boll T et al (1989) Effects of parathyroidectomy on tissue calcium, phosphorus, magnesium, and copper concentrations in aluminum-loaded uremic rats. Biol Trace Elem Res 22:45–53PubMedCrossRef
38.
go back to reference Allen MR, Iwata K, Phipps R et al (2006) Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone 39:827–829 Allen MR, Iwata K, Phipps R et al (2006) Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone 39:827–829
39.
go back to reference Atsawasuwan P, Mochida Y, Parisuthiman D et al (2005) Expression of lysyl oxidase isoforms in MC3T3-E1 osteoblastic cells. Biochem Biophys Res Commun 327:1042–1046PubMedCrossRef Atsawasuwan P, Mochida Y, Parisuthiman D et al (2005) Expression of lysyl oxidase isoforms in MC3T3-E1 osteoblastic cells. Biochem Biophys Res Commun 327:1042–1046PubMedCrossRef
40.
go back to reference Knott L, Tarlton JF, Bailey AJ (1997) Chemistry of collagen cross-linking: biochemical changes in collagen during the partial mineralization of turkey leg tendon. Biochem J 322:535–542PubMed Knott L, Tarlton JF, Bailey AJ (1997) Chemistry of collagen cross-linking: biochemical changes in collagen during the partial mineralization of turkey leg tendon. Biochem J 322:535–542PubMed
41.
go back to reference Pornprasertsuk S, Duarte WR, Mochida Y et al (2005) Overexpression of lysyl hydroxylase-2b leads to defective collagen fibrillogenesis and matrix mineralization. J Bone Miner Res 20:81–87PubMedCrossRef Pornprasertsuk S, Duarte WR, Mochida Y et al (2005) Overexpression of lysyl hydroxylase-2b leads to defective collagen fibrillogenesis and matrix mineralization. J Bone Miner Res 20:81–87PubMedCrossRef
42.
go back to reference Tang SY, Berard GP, Allen MR et al (2007) Advanced glycation end-products and mechanical properties are altered in cortical bone of beagle dogs following 1-year treatment with high-doses, but not clinically-equivalent doses, of bisphosphonates. Trans Orthop Res Soc:264 Tang SY, Berard GP, Allen MR et al (2007) Advanced glycation end-products and mechanical properties are altered in cortical bone of beagle dogs following 1-year treatment with high-doses, but not clinically-equivalent doses, of bisphosphonates. Trans Orthop Res Soc:264
43.
go back to reference Gineyts E, Allen MR, Burr DB et al (2006) Effects of antiresorptive therapy on the bone tissue concentration of enzymatic mature collagen crosslinks and pentosidine. J Bone Miner Res, supple:M344 Gineyts E, Allen MR, Burr DB et al (2006) Effects of antiresorptive therapy on the bone tissue concentration of enzymatic mature collagen crosslinks and pentosidine. J Bone Miner Res, supple:M344
44.
go back to reference Allen MR, Burr DB (2007) Mineralization, microdamage, and matrix: How bisphosphonates influence material properties of bone. BoneKEy 4:49–60 Allen MR, Burr DB (2007) Mineralization, microdamage, and matrix: How bisphosphonates influence material properties of bone. BoneKEy 4:49–60
45.
go back to reference Allen MR, Iwata K, Sato M et al (2006) Raloxifene enhances vertebral mechanical properties independent of bone density. Bone 39:1130–1135PubMedCrossRef Allen MR, Iwata K, Sato M et al (2006) Raloxifene enhances vertebral mechanical properties independent of bone density. Bone 39:1130–1135PubMedCrossRef
46.
go back to reference Iwata k, Allen MR, Follet H et al (2005) Small increases in mineralization reduce predicted bone toughness in dog following bisphosphonate treatment. Trans Orhtop Res Soc:659 Iwata k, Allen MR, Follet H et al (2005) Small increases in mineralization reduce predicted bone toughness in dog following bisphosphonate treatment. Trans Orhtop Res Soc:659
47.
go back to reference Silva MJ, Brodt MD, Wopenka B et al (2006) Decreased collagen organization and content are associated with reduced strength of demineralized and intact bone in the SAMP6 mouse. J Bone Miner Res 21:78–88PubMedCrossRef Silva MJ, Brodt MD, Wopenka B et al (2006) Decreased collagen organization and content are associated with reduced strength of demineralized and intact bone in the SAMP6 mouse. J Bone Miner Res 21:78–88PubMedCrossRef
48.
go back to reference Nakamura K, Nakazawa Y, Ienaga K (1997) Acid-stable fluorescent advanced glycation end products: vesperlysines A, B, and C are formed as crosslinked products in the Maillard reaction between lysine or proteins with glucose. Biochem Biophys Res Commun 232:227–230PubMedCrossRef Nakamura K, Nakazawa Y, Ienaga K (1997) Acid-stable fluorescent advanced glycation end products: vesperlysines A, B, and C are formed as crosslinked products in the Maillard reaction between lysine or proteins with glucose. Biochem Biophys Res Commun 232:227–230PubMedCrossRef
49.
go back to reference Tang SY, Zeenath U, Wang Y et al (2006) The in vivo formation of glycoxidative maillard products is similar between human cortical and cancellous bone. J Bone Miner Res, supple:M068 Tang SY, Zeenath U, Wang Y et al (2006) The in vivo formation of glycoxidative maillard products is similar between human cortical and cancellous bone. J Bone Miner Res, supple:M068
Metadata
Title
Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogs
Authors
M. Saito
S. Mori
T. Mashiba
S. Komatsubara
K. Marumo
Publication date
01-09-2008
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 9/2008
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-008-0585-3

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