title: Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures.
abstract: We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However, in our previous study, 1 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 properties before fractures occur. Thirty-six female beagles, 1-2 years old, were treated daily for 7 months with subcutaneous injections of saline vehicle (CNT) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechanical testing were performed. EHDP treatment suppressed intracortical and trabecular 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 the rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and by twofold in the lumbar vertebra and ilium in E-high. However, no significant 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 accumulation, but that osteoid accumulation reduces production of microdamage.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mashiba
authors.forename: C H
authors.initials: CH
authors.lastname: Turner
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: M R
authors.initials: MR
authors.lastname: Forwood
authors.forename: D S
authors.initials: DS
authors.lastname: Jacob
authors.forename: C C
authors.initials: CC
authors.lastname: Johnston
authors.forename: D B
authors.initials: DB
authors.lastname: Burr
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D012968:Etidronic Acid / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D005272:Femur Neck / Q000473:pathology / Q000503:physiopathology; D005598:Fractures, Spontaneous / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D007085:Ilium / Q000473:pathology / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D010024:Osteoporosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011859:Radiography; D012272:Ribs / Q000473:pathology / Q000503:physiopathology
chemical_list: D012968:Etidronic Acid