Antiresorptive drugs and trabecular bone turnover: validation and testing of a computer model.
A computer model of trabecular bone turnover has been developed, based on concepts of Jonathan Reeve [1]. This model predicts changes in bone volume by summing bone resorption and formation over a large number of remodeling sites. Clinical data [histomorphometry and bone mineral content (BMC)] from two clinical studies using an antiresorptive drug (etidronate disodium, EHDP) in postmenopausal osteoporosis were used to test the model. The results for BMC obtained from the EHDP and placebo groups in each study at 60 and 120 weeks were correctly predicted by the model from the histomorphometric data obtained from baseline and week 60 biopsies. The parameter in this model having the greatest influence on predicted changes in bone volume was found by sensitivity analysis to be activation frequency. These results suggest that the contribution of bone turnover to BMC can be predicted solely by considering the cell kinetics of the basic multicellular unit (BMU), and that, in the case of antiresorptive drugs, maximal effects on bone volume may be achieved by pharmacological reduction of activation frequency. The results also suggest that the present model may be useful in predicting in clinical studies the effects of EHDP and similar drugs on bone turnover.
Lacy
M E
ME
Procter & Gamble Pharmaceuticals, Miami Valley Laboratory, Cincinnati, Ohio 45239-8707.
Bevan
J A
JA
Boyce
R W
RW
Geddes
A D
AD
D015502:Absorptiometry, Photon; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003198:Computer Simulation; D012968:Etidronic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008954:Models, Biological; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism
D012968:Etidronic Acid