BISPHOSPHONATE EFFECTS AND THE BONE REMODELING TRANSIENT

Published randomized clinical trial data for alendronate, given at a d ose of 10 mg/day, were fitted by a computer algorithm to the currently accepted model of the bone remodeling process, The purpose was to det ermine how much of the reported improvement in lumbar spine bone densi ty could be attributed to the inevitable remodeling transient and how much might represent positive bone balance. Very good fits to the clin ical data were easily obtained, indicating the general validity of cur rent syntheses of bone remodeling biology. The best fit was provided b y simulations produced by combinations of 36-38% suppression of remode ling activation and positive remodeling balance ranging from 1.1 to 1. 4% per year, Whole body bone biomarker changes would have suggested bo th a slightly greater degree of suppression and a higher baseline leve l of remodeling than could be provided by any of the simulations if th ey were to fit the clinical data, Either regional skeletal heterogenei ty or lack of a one-to-one quantitative relationship between remodelin g changes and biomarker changes may explain the discrepancies between the two approaches.