Mechanical evaluation of bone samples following alendronate therapy in healthy male dogs

Abstract

Alendronate and other bisphosphonates are clinically efficacious in treating postmenopausal osteoporosis, Paget's disease and hypercalcemia associated with malignancy. Because bisphosphonates are being considered for use in younger patients with joint replacements to prevent osteolysis, and for stress fracture prophylaxis in military recruits, it is important to know how bisphosphonate therapy affects healthy bone. We sought to determine whether bones from healthy male dogs exhibit alterations in structural or mechanical properties following alendronate treatment for 23 weeks. We tested trabecular tissue samples in compression and determined tissue ash density. We tested whole long bones in bending and torsion. For trabecular samples, we evaluated trabecular modulus, strength, and density. For whole bone specimens, we compared structural stiffness and ultimate load. We found no significant differences in any measure, between canines treated with alendronate for 23 weeks and controls, although we found consistent trends toward higher properties in the treated group. Correlation analysis revealed significant relationships between stiffness and strength measures for each mechanical test. Our results indicate bisphosphonate treatment in healthy canines does not weaken the properties of bone. The trends indicate a slight positive overall effect of alendronate treatment on the mechanical properties of healthy canine bone.

Anabolic effects of bisphosphonates on peri-implant bone stock

“…Our previous investigations of femora in a canine total hip arthroplasty model demonstrated that a prolonged bisphosphonate treatment over 23 weeks did not alter whole bone mechanical properties, such as fracture toughness, elastic modulus, or tensile strength [33]. In a separate evaluation, the torsional properties of bisphosphonate-treated bones were also unchanged, as were the trabecular modulus, strength and density [9]. Histomorphometric data similarly demonstrate no adverse effects on bone structure or mineralization [48].…”

“…Clinically, thicker peri-implant cortical bone improves the torsional strength of the bone as suggested by significantly increased polar moment of inertia. Our previous studies have demonstrated that bisphosphonate treatment over 23 weeks does not compromise the structural or mechanical properties of the bone [9,33].…”

“…A better understanding of the molecular biological mechanisms that generate particle-induced osteolysis has raised the possibility of potential pharmacological interventions [7,8]. We have focused on bisphosphonates as possible candidates for prevention and medical treatment of peri-implant osteolysis [8][9][10][11].…”

Assessment of vertebral fracture risk and therapeutic effects of alendronate in postmenopausal women using a quantitative computed tomography-based nonlinear finite element method

“…This assumption is based on a study which found that, in ovariectomized baboons, 2 years of alendronate treatment did not alter the mechanical properties of cortical tissue or the nonlinear strength-density correlation for trabecular bone [41]. In addition, a study on healthy male dogs showed that 23 weeks of alendronate treatment did not alter mechanical properties of trabecular bone [42]. Other limitations were that this study was a nonrandomized drug study, and only eight subjects were included in the untreated group.…”

Ibandronate treatment for osteoporosis: Rationale, preclinical and clinical development of extended dosing regimens

“…Currently available bisphosphonates, notably alendronate, risedronate, and zoledronate, have been extensively tested in animal models [8,[17][18][19][20][21][22][23][24][25]. In ovariectomized rats and nonhuman primates, these agents were shown to prevent bone turnover, while increasing BMD [8,[17][18][19][20][21].…”