To elaborate the understanding of diphosphonate kinetics, a non compartmental analysis is introduced. Using continuous infusion of 99mTc-methylene diphosphonate (Tc-MDP) and 51Cr-EDTA, as a cotracer, the diphosphonate clearance to bone (BDC) can be calculated. BDC is found to correlate well with the 24 h whole body retention of diphosphonate (WBR) (r = 0.89, P less than 0.01) when renal function is normal, but not in cases of reduced 51Cr-EDTA clearance. These findings indicate that BDC measurements are superior to the WBR technique in the estimation of bone turnover, especially when renal function is reduced. The BDC measurements may also constitute a useful tool for studies of diphosphonate uptake in bone, the foundation of bone scintigraphy.