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


BACKGROUND
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).


CONCLUSIONS
Long-term suppression of bone remodeling by bisphosphonate increases degree of mineralization, collagen maturity, and non-enzymatic cross-linking.
Saito
M
M
Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan. xlink67@gol.com
Mori
S
S
Mashiba
T
T
Komatsubara
S
S
Marumo
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001862:Bone Resorption / Q000503:physiopathology / Q000517:prevention & control; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D010758:Phosphorus / Q000378:metabolism; D012272:Ribs / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D017127:Glycation End Products, Advanced; C071542:cimadronate; D010758:Phosphorus; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008239:Lysine; D002118:Calcium