Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures

We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However , in our previous study, I year treatment with high-dose etidronate (EHDP) did not increase microdamage accumulation in most skeletal sites of dogs in spite of complete remodeling suppression and the occurrence of spontaneous fractures of ribs and/or thoracic spinous processes. This study evaluates the effects of EHDP on microdamage accumulation and biomechanical propertie s before fractures occur. Thirty-six female beagles, 1-2 years old, were tr eated daily for 7 months with subcutaneous injections of saline vehicle (CN T) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechani cal testing were performed. EHDP treatment suppressed intracortical and tra becular remodeling by 60%-75% at the lower dose, and by 100% at the higher dose. Osteoid accumulation caused by a mineralization deficit occurred only in the E-high group, and this led to a reduction of mineralized bone mass. Microdamage accumulation increased significantly by two- to fivefold in th e rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and b y twofold in the lumbar vertebra and ilium in E-high. However, no significa nt increase in damage accumulation was observed in ribs or thoracic spinous processes in E-high where fractures occur following 12 months of treatment . Mechanical properties of lumbar vertebrae and thoracic spinous processes were reduced significantly in both E-low and E-high. These findings suggest that suppression of bone remodeling by EHDP allows microdamage accumulatio n, but that osteoid accumulation reduces production of microdamage. (Bone 2 9:271-278; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.