This article discusses methods for quantifying bone turnover based on tracer kinetic studies of the short-lived radiopharmaceuticals 99mTc-MDP and 18F-fluoride. Measurements of skeletal clearance obtained by using these tracers reflect the combined effects of skeletal blood flow and osteoblastic activity. The pharmacokinetics of each tracer is described, together with some of the quantitative tests of skeletal function that have been described in the literature. The physiologic interpretation of quantitative measurements of bone obtained with the use of short half-life radionuclides is discussed, and the advantages and limitations of 99mTc-MDP and 18F-fluoride are compared and contrasted. Currently, 18F-fluoride dynamic positron emission tomography (PET) is the technique of choice for physiologically precise quantitative studies of bone. However, comparable data could probably be obtained by using 99mTc-MDP if methods for single photon emission computed tomography (SPECT) quantitation were improved.