Recovery from pamidronate (APD): a two-year study in the dog.
The goal of this study was to find out if bone can recover after long-term administration of bisphosphonate. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5, and 25 mg/kg/day for 1 year (0.1% concentration) and the animals were allowed to recover for another year. At sacrifice, the os ilium was used to determine bone mineralization profile and, subsequently, each density fraction was analyzed chemically. The ribs were used to determine the lattice parameters and the size of the apatite crystals of bone. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and, subsequently, to determine bone mechanical properties using a 3-point bending technique. We found that the 12.5 and 25 mg/kg/day doses exhibit a significant shift towards greater mineralization versus control, whereas the lower dose (2.5 mg/kg/day) was indistinguishable from the controls. The lattice parameters and crystal size of bone apatite remained unchanged. The image analysis shows a dose-related increase in trabecular volume and thickness. The connectivity increased with dose but the anisotropy of bone remained unchanged. Both the elastic modulus and the maximum stress of bone remain unaffected by APD. We conclude that when dogs are treated with APD for 1 year, their bones can reestablish their physical-chemical characteristics (mineralization profile, chemistry, and crystal size/strain) after 1 year of recovery, provided that the treatment dose is 2.5 mg/kg/day. In addition, the mechanical properties of the bone remained unaffected and the gains in trabecular volume and thickness are maintained.
Grynpas
M D
MD
Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Kasra
M
M
Dumitriu
M
M
Nespeca
R
R
Very
J M
JM
Mertz
B P
BP
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005260:Female; D008297:Male; D000077268:Pamidronate; D013314:Stress, Mechanical; D013997:Time Factors
D004164:Diphosphonates; D000077268:Pamidronate