Effects of the bisphosphonate tiludronate on bone resorption, calcium balance, and bone mineral density.
Bone resorption inhibitors, such as bisphosphonates, are potentially useful in treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has proven efficacious in preventing bone loss in postmenopausal women. However, it is not clearly established whether bisphosphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose-dependent decrease in retinoid-stimulated bone resorption. It increased the intestinal absorption and body retention of calcium. In OVX rats it caused a time- and dose-dependent increase in BMD at the level of the three investigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appeared to induce similar increases in BMD. These results indicate that tiludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.
Ammann
P
P
Department of Medicine, University Hospital, Geneva, Switzerland.
Rizzoli
R
R
Caverzasio
J
J
Shigematsu
T
T
Slosman
D
D
Bonjour
J P
JP
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D010052:Ovariectomy; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012176:Retinoids / Q000494:pharmacology; D013965:Thyroidectomy
D001565:Benzoates; D004164:Diphosphonates; D012176:Retinoids; C058651:tiludronic acid; C034814:ethyl-p-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl)benzoic acid; D002118:Calcium