Alendronate treatment results in similar levels of trabecular bone remodeling in the femoral neck and vertebra

Introduction Bone turnover suppression in sites that already have a low surface-based remodeling rate may lead to oversuppression that could have negative effects on the biomechanical properties of bone. The goal was to determine how alendronate suppresses bone turnover at sites with different surface-based remodeling rates. Methods Dynamic histomorphometric parameters were assessed in trabecular bone of the femoral neck and lumbar vertebrae obtained from skeletally mature beagles treated with saline (1 ml/kg/day) or alendronate (ALN 0.2 or 1.0 mg/kg/day). The ALN0.2 and ALN1.0 doses approximate, on a milligram per kilogram basis, the clinical doses used for the treatment of postmenopausal osteoporosis and Paget’s disease, respectively. Results Alendronate treatment resulted in similar absolute levels of bone turnover in the femoral neck and vertebrae, although the femoral neck had 33% lower pre-treatment surface-based remodeling rate than the vertebra (p < 0.05). Additionally, the high dose of alendronate (ALN 1.0) suppressed bone turnover to similar absolute levels as the low dose of alendronate (ALN 0.2) in both sites. Conclusions Alendronate treatment may result in a lower limit of trabecular bone turnover suppression, suggesting that sites of low pre-treatment remodeling rate are not more susceptible to oversuppression than those of high pre-treatment remodeling rate

Effects of 1 to 3 years' treatment with alendronate on mechanical properties of the femoral shaft in a canine model: implications for subtrochanteric femoral fracture risk

Bisphosphonate (BP) treatment used to prevent bone loss in postmenopausal osteoporosis has recently been implicated in an apparent increase in subtrochanteric femoral fractures. Previous work showed that BPs can reduce the energy to fracture of cancellous bone, but limited data exist on material-level mechanical properties of compact bone from the long bones. This study examined intrinsic mechanical properties of the femoral diaphysis of a canine model treated for 1 or 3 years with alendronate at two different doses. Seventy-two dogs were treated orally with 0.2 mg/kg/day alendronate or 1.0 mg/kg/day alendronate; a control group was administered saline. Prismatic beam specimens were tested in four-point bending under displacement control, and the intrinsic mechanical properties were calculated. No significant differences were found among groups in any mechanical property at either 1 or 3 years of treatment. We conclude that the material properties of the femoral diaphysis are not degraded following 1 to 3 years treatment with alendronate, even at high doses. Longer periods of treatment have not been studied using clinical doses of alendronate, but such studies need to be carried out to confirm a lack of effect of alendronate on mechanical properties of cortical bone in the subtrochanteric region of the femur

One Year of Alendronate Treatment Lowers Microstructural Stresses Associated with Trabecular Microdamage Initiation

Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage

Effects of 1 to 3 years' treatment with alendronate on mechanical properties of the femoral shaft in a canine model: implications for subtrochanteric femoral fracture risk

Bisphosphonate (BP) treatment used to prevent bone loss in postmenopausal osteoporosis has recently been implicated in an apparent increase in subtrochanteric femoral fractures. Previous work showed that BPs can reduce the energy to fracture of cancellous bone, but limited data exist on material-level mechanical properties of compact bone from the long bones. This study examined intrinsic mechanical properties of the femoral diaphysis of a canine model treated for 1 or 3 years with alendronate at two different doses. Seventy-two dogs were treated orally with 0.2 mg/kg/day alendronate or 1.0 mg/kg/day alendronate; a control group was administered saline. Prismatic beam specimens were tested in four-point bending under displacement control, and the intrinsic mechanical properties were calculated. No significant differences were found among groups in any mechanical property at either 1 or 3 years of treatment. We conclude that the material properties of the femoral diaphysis are not degraded following 1 to 3 years treatment with alendronate, even at high doses. Longer periods of treatment have not been studied using clinical doses of alendronate, but such studies need to be carried out to confirm a lack of effect of alendronate on mechanical properties of cortical bone in the subtrochanteric region of the femur

One Year of Alendronate Treatment Lowers Microstructural Stresses Associated with Trabecular Microdamage Initiation

Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage