A Prospective Study of Risedronate on Regional Bone Metabolism and Blood Flow at the Lumbar Spine Measured by18F-Fluoride Positron Emission Tomography

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Abstract
The effect of risedronate on bone metabolism at the lumbar spine was assessed in 18 women who had a 18F-fluoride PET scan at baseline and after 6 months of therapy. The net plasma clearance of fluoride to bone mineral reflecting osteoblastic activity decreased significantly after therapy. Quantitative radionuclide studies of bone reflect bone blood flow and regional osteoblastic activity, and the latter should change after treatment with a bisphosphonate, although this has not been previously demonstrated. The aim of this study was to examine regional 18F-fluoride kinetics in the lumbar spine measured by 18F-fluoride positron emission tomography (PET) before and after treatment with risedronate. Eighteen women, with a mean age of 67.0 years and a T-score of less than -2 at the spine or hip, had a dynamic PET scan of the lumbar spine after the injection of 90 MBq 18F-fluoride ion at baseline and 6 months after commencing risedronate therapy. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were measured by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K(1)) and the net plasma clearance of tracer to bone mineral (K(i)). Rate constants k(2), k(3), and k(4), which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, respectively, were also measured. Mean vertebral K(i) decreased significantly by 18.4% from baseline (3.32 x 10(-2) ml/min/ml) to 6 months post-treatment (2.71 x 10(-2) ml/min/ml; p = 0.04). This decrease was similar in magnitude to the decrease observed for bone-specific alkaline phosphatase, a marker of bone formation. There was no significant difference in K(1) from baseline (1.49 x 10(-1) ml/min/ml) to 6 months after treatment (1.38 x 10(-1) ml/min/ml; p > 0.05). There was a significant increase in k(2), reflecting the reverse transport of fluoride from the extravascular tissue compartment to plasma, after 6 months of treatment (2.90 x 10(-1)/min versus 4.43 x 10(-1)/min; p = 0.01). No significant changes were seen for k(3) or k(4). There was a significant decrease from baseline in the fraction of tracer in the extravascular tissue space that underwent specific binding to the bone matrix (k(3)/[k(2) + k(3)]), decreasing by 18.1% (p = 0.02). K(i), the net plasma clearance to bone mineral reflecting regional osteoblastic activity, displayed a significant decrease after 6 months of antiresorptive therapy. This is the first study to show a direct metabolic effect of antiresorptive therapy on skeletal kinetics at the clinically important site of the lumbar spine. The use of 18F-fluoride PET may provide a useful noninvasive tool to assess novel treatments currently being developed for osteoporosis.