Changes in bone mineralization, architecture and mechanical properties due to long-term (1 year) administration of pamidronate (APD) to adult dogs.
The goal of this study was to evaluate the effect of 1 year of APD administration on bone mineralization and bone mineral chemistry in the dog. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5 and 25.0 mg/kg per day (0.1% concentration for 12 months) as part of a long-term toxicity study. The os ilium and a vertebra were used to determine the mineralization profile and, subsequently, each density fraction was analysed chemically. The ribs were used to determine lattice parameters of the apatite crystal size using X-ray diffraction. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and subsequently to determine mechanical properties using velocity-of-sound techniques. We found that for both the ilium and the vertebrae there was a significant shift of the mineralization profile towards greater density in a dose-related manner. This effect levelled off with the highest dose because the shift in mineralization profile correlated better with the square root of the dose than with the dose. Together with data on crystal size, which show an increase in lattice parameters and a decrease in crystal size with dose, our data lead us to believe that long-term administration of APD leads to an increase in bone mineralization without major changes in bone chemistry of Ca, Mg, and P and with a decrease in bone apatite crystal size. The image analysis shows a dose-related increase in trabecular bone volume and thickness.(ABSTRACT TRUNCATED AT 250 WORDS)
Grynpas
M D
MD
Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Canada.
Acito
A
A
Dimitriu
M
M
Mertz
B P
BP
Very
J M
JM
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects*; D005591:Chemical Fractionation; D004164:Diphosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D000077268:Pamidronate; D011859:Radiography; D013997:Time Factors; D014463:Ultrasonography; D014961:X-Ray Diffraction
D004164:Diphosphonates; D000077268:Pamidronate