Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption.