title: Assessment of regional changes in skeletal metabolism following 3 and 18 months of teriparatide treatment.
abstract: Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium-99m methylene diphosphonate ((99m)Tc-MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 microg/day subcutaneously. Subjects were injected with 600 MBq (99m)Tc-MDP, and whole-body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free (99m)Tc-MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole-skeleton K(bone) were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional K(bone) values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole-skeleton K(bone). This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics.
authors.affiliation: King's College London, Guy's Campus, London, United Kingdom. amelia.moore@kcl.ac.uk
authors.forename: Amelia E B
authors.initials: AE
authors.lastname: Moore
authors.forename: Glen M
authors.initials: GM
authors.lastname: Blake
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Taylor
authors.forename: Asad E
authors.initials: AE
authors.lastname: Rana
authors.forename: Mayme
authors.initials: M
authors.lastname: Wong
authors.forename: Peiqi
authors.initials: P
authors.lastname: Chen
authors.forename: Ignac
authors.initials: I
authors.lastname: Fogelman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism*; D024042:Collagen Type I / Q000652:urine; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000652:urine; D011347:Procollagen / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013669:Technetium Tc 99m Medronate; D019379:Teriparatide / Q000627:therapeutic use*
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D019275:Radiopharmaceuticals; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D019379:Teriparatide; D000469:Alkaline Phosphatase; D013669:Technetium Tc 99m Medronate