Quantitative Measurements of Bone Remodeling Using 99mTc-Methylene Diphosphonate Bone Scans and Blood Sampling

Abstract

Quantitative studies of bone using (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) have a potentially valuable role in investigating the treatment of patients with metabolic bone disease. In this study we compared 3 different methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) in 12 osteoporotic postmenopausal women (mean age, 67.3 y) before participation in a clinical trial of an osteoporosis therapy. The aim was to compare the consistency and accuracy of the 3 methods before their use in evaluating the subjects' response to treatment. Subjects were injected with 600 MBq (99m)Tc-MDP and 3 MBq (51)Cr-ethylenediaminetetraacetic acid ((51)Cr-EDTA) and whole-body bone scan images were acquired at 10 min, 1, 2, 3, and 4 h. Two-minute static images of the thighs were acquired immediately after the 1- to 4-h whole-body scans. Six blood samples were taken between 5 min and 4 h, and free (99m)Tc-MDP was measured using ultrafiltration. The glomerular filtration rate (GFR) was estimated from the (51)Cr-EDTA plasma curve. The methods used to evaluate K(bone) were (a) the area-under-the-curve (AUC) method, in which the GFR measurement was subtracted from the total (bone plus renal) clearance (K(total)) measured from the free (99m)Tc-MDP plasma curve; (b) the modified Brenner method, in which (99m)Tc-MDP renal clearance estimated from the whole-body counts was subtracted from the total clearance measured from the rate of elimination of tracer from soft tissue; and (c) the Patlak plot method, which was also used to derive regional values of K(bone) for the skull, spine, pelvis, arms, and legs. There was good agreement between the 3 methods of measuring K(bone). (mean K(bone) +/- SD: AUC method, 30.3 +/- 6.4 mL x min(-1); Brenner method, 31.1 +/- 5.8 mL x min(-1); Patlak method, 35.7 +/- 5.8 mL x min(-1)). The correlation coefficients between the methods varied from r = 0.767 (P = 0.004) to r = 0.805 (P = 0.002). Regional measurements of (99m)Tc-MDP clearance gave the following percentages of the whole-skeleton clearance: skull, 13.3%; spine, 16.6%; pelvis, 17.2%; arms, 11.1%; legs, 23.7%. The 3 methods gave consistent and accurate measurements of K(bone). The Patlak method can be used to study regional as well as total-skeleton values of K(bone).