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Clinical Investigations |
1 Department of Nuclear Medicine, Guy’s Hospital, London, United Kingdom
Quantitative radionuclide studies of bone using the short-lived tracers 18F-fluoride and 99mTc-methylene diphosphonate (MDP) are an alternative method to biochemical markers of bone turnover for investigating the dynamic state of the skeleton. In this study we evaluated their use to quantify bone turnover in women receiving antiresorptive therapy compared with that of untreated control subjects. Methods: The patients were 69 healthy postmenopausal women. Twenty-six women were receiving hormone replacement therapy (HRT) and 43 were untreated age-matched control subjects. After bolus injection of 18F-fluoride (1 MBq), 99mTc-MDP (1 MBq), 51Cr-ethylenediaminetetraacetic acid (3 MBq), and 125I-labeled human serum albumin (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h. The clearance to bone mineral Kbone was first evaluated using the area under the plasma concentration curve (AUC) on the assumption that the rate constant k4 for the outflow of tracer from bone was negligibly small. AUC values of Kbone were then compared with those found using a compartmental model method that allowed k4 to be fitted as a free parameter. Results: Using the AUC method the mean ± SD for Kbone for the 2 tracers were: 18F-fluoride, 61.8 ± 12.0 mL · min-1 (HRT group) versus 67.2 ± 12.6 mL · min-1 (control group) (P = 0.045); and 99mTc-MDP, 40.3 ± 8.2 mL · min-1 (HRT group) versus 44.2 ± 7.6 mL · min-1 (control group) (P = 0.024). Values for the 2 tracers in individual patients were moderately well correlated (r = 0.76; P < 0.001). Using the compartmental model method, k4 for 18F-fluoride was shown to lie in the range 0–0.0025 min-1 with a best-fit value of 0.0018 min-1. Values of Kbone determined using k4 = 0.0018 min-1 were highly correlated with the AUC values (r = 0.989; SEE = 2.05 mL · min-1) with numeric values that were larger by a factor of 1.53. Analysis of the 99mTc-MDP data was more difficult because of uncertainties in protein binding in the extracellular fluid compartment space. The best fit for k4 was in the range 0.0010–0.0014 min-1 with values of Kbone similar to those found using the AUC method. Conclusion: Values of Kbone determined using the AUC method were able to differentiate between HRT-treated women and postmenopausal women who were not treated and were highly correlated with those determined using a compartmental model method with nonzero values of k4.
Key Words: bone turnover • 18F-fluoride • 99mTc-methylene diphosphonate
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