Browsing by Subject "risedronate"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Bisphosphonates alter trabecular bone collagen cross-linking and isomerization in beagle dog vertebra
    (2008-03) Allen, Matthew R.; Gineyts, Evelyne; Leeming, Diana J.; Burr, David B.; Delmas, Pierre D.
    Changes 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. INTRODUCTION: The 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. METHODS: Skeletally 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 alpha/beta C-telopeptide [CTX]), enzymatic (pyridinoline [PYD] and deoxypyridinoline [DPD]), and non-enzymatic (pentosidine [PEN]) cross-links. RESULTS: All doses of both RIS and ALN increased PEN (+34-58%) and the ratio of PYD/DPD (+14-26%), and decreased the ratio of alpha/beta CTX (-29-56%) compared to VEH. RAL did not alter any collagen parameters. Bone turnover rate was significantly correlated to PEN (R = -0.664), alpha/beta CTX (R = 0.586), and PYD/DPD (R = -0.470). CONCLUSIONS: Bisphosphonate treatment significantly alters properties of bone collagen suggesting a contribution of the organic matrix to the anti-fracture efficacy of this drug class.
  • Thumbnail Image
    Item
    Changes in vertebral strength-density and energy absorption-density relationships following bisphosphonate treatment in beagle dogs
    (2008-01) Allen, Matthew R.; Burr, David B.
    We aimed to determine the effects of bisphosphonates on mechanical properties independent of changes in bone density. Our results show that at equivalent bone densities, vertebrae from beagles treated with bisphosphonate have equivalent bone strength and reduced bone energy absorption compared to those from untreated animals. INTRODUCTION: Assessing the relationship between mechanical properties and bone density allows a biomechanical evaluation of bone quality, with differences at a given density indicative of altered quality. The purpose of this study was to evaluate the strength-density and energy absorption-density relationships in vertebral bone following a one-year treatment with clinical doses of two different bisphosphonates in beagle dogs. METHODS: Areal bone mineral density (aBMD) and compressive mechanical properties (ultimate load and energy absorption) were assessed on lumbar vertebrae from skeletally mature beagle dogs treated with vehicle (VEH), alendronate (ALN), or risedronate (RIS). Relationships among properties were assessed using analyses of covariance. RESULTS: Neither treatment altered the strength-density relationship compared to VEH, suggesting increases in vertebral strength with bisphosphonate-treatment are explained by increased density. The energy absorption-density relationship was altered by ALN, resulting in significantly lower energy absorption capacity at a given aBMD compared to both VEH (-22%) and RIS (-14%). CONCLUSIONS: These data document that after adjusting for increased aBMD, vertebrae from animals treated with bisphosphonates have similar strength as those from untreated animals. Conversely, when adjusted for increased aBMD, alendronate treatment, but not risedronate treatment, significantly reduces the energy required for vertebral fracture, indicative of an alteration in bone quality.