title: Radionuclide studies of bone metabolism: do bone uptake and bone plasma clearance provide equivalent measurements of bone turnover?
abstract: Quantitative radionuclide imaging using (18)F-fluoride positron emission tomography (18F-PET) or (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans provides a novel tool for studying regional and whole skeleton bone turnover that complements the information provided by biochemical markers. Radionuclide bone scans can be quantified by measuring either tracer uptake or, if blood sampling is performed, bone plasma clearance. This study examines whether these two methods provide equivalent information about bone turnover. We examined data from two clinical trials of the bone anabolic agent teriparatide. In Study 1 twenty osteoporotic women had 18F-PET scans of the lumbar spine at baseline and after 6 months treatment with teriparatide. Bone uptake in the lumbar spine was expressed as standardised uptake values (SUV) and blood samples taken to evaluate plasma clearance. In Study 2 ten women had (99m)Tc-MDP scans at baseline, 3 and 18 months after starting teriparatide. Blood samples were taken and whole skeleton plasma clearance and bone uptake calculated. In Study 1 spine plasma clearance increased by 23.8% after 6-months treatment (P=0.0003), whilst SUV increased by only 3.0% (P=0.84). In Study 2 whole skeleton plasma clearance increased by 37.1% after 18-months treatment (P=0.0002), whilst the 4-hour whole skeleton uptake increased by only 25.5% (P=0.0001). During treatment the 18F- plasma concentration decrease by 20% and (99m)Tc-MDP concentration by 13%, and these latter changes were sufficient to explain the differences between the uptake and plasma clearance results. Measurements of response to treatment using bone uptake and plasma clearance gave different results because the effects of teriparatide on bone resulted in a sufficiently increased demand for radionuclide tracer from the skeleton that the concentration in the circulation decreased. Similar effects may occur with other therapies that have a large enough effect on bone metabolism. In these circumstances changes in bone plasma clearance give a truer impression of response to treatment than those in SUV or uptake.
authors.affiliation: Division of Imaging Sciences, King's College London, Guy's Campus, London, UK. glen.blake@kcl.ac.uk
authors.forename: Glen M
authors.initials: GM
authors.lastname: Blake
authors.forename: Musib
authors.initials: M
authors.lastname: Siddique
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Frost
authors.forename: Amelia E B
authors.initials: AE
authors.lastname: Moore
authors.forename: Ignac
authors.initials: I
authors.lastname: Fogelman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011859:Radiography; D019275:Radiopharmaceuticals / Q000378:metabolism; D013669:Technetium Tc 99m Medronate / Q000378:metabolism; D019379:Teriparatide / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019379:Teriparatide; D013669:Technetium Tc 99m Medronate