GFR-corrected 24-hour whole body retention of diphosphonate: an improved index of bone metabolism

The 24-hour whole body retention of diphosphonate (WBR) depends on bone uptake and renal clearance of diphosphonate. To evaluate the influence of glomerular filtration we measured WBR, creatinine clearance (CrCl) and s-alkaline phosphatase (s-AP) in 91 normals and 79 patients with different calcium metabolic disorders. As presumed, a negative correlation between CrCl and WBR exists (r = -0.67, p less than 0.001). By defining CrCl = 100 ml/min as standard, we have introduced a new mathematical model which allows recalculation of the measured WBR to WBR at CrCl = 100 ml/min (WBR100): WBR100 = [(1-WBR) x 100/WBR x CrCl +1]-1 Whole body retention at a clearance of 100 ml/min is demonstrated to be independent of CrCl (r = 0.14, NS). Using this approach we estimate that deviations of CrCl below 70 ml/min and above 150 ml/min lead to more than 25% increase/decrease in WBR. Using s-alkaline phosphatase as a standard, it is shown that WBR overestimates bone formation when CrCl is low. This new model permits the interpretation of WBR measurements in terms of bone turnover in patients with low glomerular filtration rates.