Evelyne Gineyts

Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra

SummaryChanges in organic matrix may contribute to the anti-fracture efficacy of anti-remodeling agents. Following one year of treatment in beagle dogs, bisphosphonates alter the organic matrix of vertebral trabecular bone, while raloxifene had no effect. These results show that pharmacological suppression of turnover alters the organic matrix component of bone.IntroductionThe collagen matrix contributes significantly to a bone’s fracture resistance yet the effects of anti-remodeling agents on collagen properties are unclear. The goal of this study was to assess changes in collagen cross-linking and isomerization following anti-remodeling treatment.MethodsSkeletally mature female beagles were treated for one year with oral doses of vehicle (VEH), risedronate (RIS; 3 doses), alendronate (ALN; 3 doses), or raloxifene (RAL; 2 doses). The middle dose of RIS and ALN and the lower dose of RAL approximate doses used for treatment of post menopausal osteoporosis. Vertebral trabecular bone matrix was assessed for collagen isomerization (ratio of α/β C-telopeptide [CTX]), enzymatic (pyridinoline [PYD] and deoxypyridinoline [DPD]), and non-enzymatic (pentosidine [PEN]) cross-links.ResultsAll doses of both RIS and ALN increased PEN (+34–58%) and the ratio of PYD/DPD (+14–26%), and decreased the ratio of α/β CTX (−29–56%) compared to VEH. RAL did not alter any collagen parameters. Bone turnover rate was significantly correlated to PEN (Ru2009=u2009−0.664), α/β CTX (Ru2009=u20090.586), and PYD/DPD (Ru2009=u2009−0.470).ConclusionsBisphosphonate treatment significantly alters properties of bone collagen suggesting a contribution of the organic matrix to the anti-fracture efficacy of this drug class.

Relationships between human cortical bone toughness and collagen cross-links on paired anatomical locations

Human cortical bone fracture processes depend on the internal porosity network down to the lacunar length scale. Recent results show that at the collagen scale, the maturation of collagen cross-links may have a negative influence on bone mechanical behavior. While the effect of pentosidine on human cortical bone toughness has been studied, the influence of mature and immature enzymatic cross-links has only been studied in relation to strength and work of fracture. Moreover, these relationships have not been studied on different paired anatomical locations. Thus, the aim of the current study was to assess the relationships between both enzymatic and non-enzymatic collagen cross-links and human cortical bone toughness, on four human paired anatomical locations. Single Edge Notched Bending toughness tests were performed for two loading conditions: a quasi-static standard condition, and a condition representative of a fall. These tests were done with 32 paired femoral diaphyses, femoral necks and radial diaphyses (18 women, age 81u202f±u202f12u202fy.o.; 14 men, age 79u202f±u202f8u202fy.o.). Collagen enzymatic and non-enzymatic crosslinks were measured on the same bones. Maturation of collagen was defined as the ratio between immature and mature cross-links (CX). The results show that there was a significant correlation between collagen cross-link maturation and bone toughness when gathering femoral and radial diaphyses, but not when considering each anatomical location individually. These results show that the influence of collagen enzymatic and non-enzymatic cross-links is minor when considering human cortical bone crack propagation mechanisms.

Relationships between cortical bone quality biomarkers: Stiffness, toughness, microstructure, mineralization, cross-links and collagen

Bone quality encompasses bone properties that contribute to fracture risk, such as bone stiffness, microstructure, matrix constituents or tissue material properties. These aspects cannot be quantified in-vivo except for stiffness, a surrogate biomarker of strength, which can be assessed using quantitative ultrasound techniques. To better predict bone fracture risk, investigating the relationships between stiffness and other bone quality factors is important. Toward this goal, our group adapted resonant ultrasound spectroscopy (RUS) to precisely measure the whole set of stiffness coefficients of cortical bone by improving the signal processing and automatizing the inversion procedure based on a Bayesian framework. In this work, we present the relationships between bone quality biomarkers including stiffness, fracture toughness, microstructure, mineralization, cross-links and collagen.