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

T. Mashiba, C. H. Turner, T. Hirano, M. R. Forwood, D. S. Jacob, C. C. Johnston, David Burr

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalBone
Volume29
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Etidronic Acid
Spontaneous Fractures
Bone and Bones
Lumbar Vertebrae
Ribs
Thorax
Ilium
Bone Remodeling
Therapeutics
Subcutaneous Injections
Minerals
Dogs

Keywords

  • Biomechanics
  • Bisphosphonates
  • Bone remodeling
  • Histomorphometry
  • Microdamage
  • Osteoporosis

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures. / Mashiba, T.; Turner, C. H.; Hirano, T.; Forwood, M. R.; Jacob, D. S.; Johnston, C. C.; Burr, David.

In: Bone, Vol. 29, No. 3, 2001, p. 271-278.

Research output: Contribution to journalArticle

Mashiba, T. ; Turner, C. H. ; Hirano, T. ; Forwood, M. R. ; Jacob, D. S. ; Johnston, C. C. ; Burr, David. / Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures. In: Bone. 2001 ; Vol. 29, No. 3. pp. 271-278.
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