Long-term safety of the aminobisphosphonate alendronate in adult dogs. II. Histomorphometric analysis of the L5 vertebrae.
Osteoporosis is a major health problem. Bisphosphonates are synthetic compounds that are taken up preferentially by the skeleton and suppress osteoclast-mediated bone resorption. Alendronate (ALN) is an aminobisphosphonate used in the treatment of diseases characterized by increased bone resorption including osteoporosis. The purpose of this study was to rule out possible adverse effects of the chronic administration of ALN on the quality of bone. Thirty-one 20- to 21-month-old beagles (n = 7-8 per group, females and males) were treated p.o. for 157 weeks with ALN at 0.00, 0.25, 0.5 or 1.00 mg/kg/day and labeled in vivo with oxytetracycline and calcein. Undecalcified bone sections obtained from the fifth lumbar vertebra were evaluated by static and dynamic histomorphometry. Cortical or cancellous bone volume and indices of architecture were not affected by treatment. Osteoid thickness and mineralization lag time were not changed by treatment. Tissue level bone turnover was inhibited in a dose-dependent manner in males. The results indicate that long-term ALN administration at up to 5 times the dose used for treatment of osteoporosis in clinical trials causes no abnormalities in bone remodeling or bone structure.
Balena
R
R
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Markatos
A
A
Seedor
J G
JG
Gentile
M
M
Stark
C
C
Peter
C P
CP
Rodan
G A
GA
D019386:Alendronate; D000818:Animals; D001696:Biomechanical Phenomena; D001846:Bone Development / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D004164:Diphosphonates / Q000633:toxicity*; D004285:Dogs; D005260:Female; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D013997:Time Factors
D004164:Diphosphonates; D019386:Alendronate