title: Differential effects of teriparatide on regional bone formation using (18)F-fluoride positron emission tomography.
abstract: Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study (18)F-fluoride plasma clearance (K(i)) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K(i) values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K(i) values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k(3)/[k(2) + k(3)]), which increased by 23% (p = .0006). In contrast to K(i) , spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K(i) and SUVs was explained by a 20% decrease in (18)F(-) plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by (18)F(-) PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites.
authors.affiliation: Osteoporosis Research Unit, Division of Imaging Sciences, King's College London, Guy's Campus, London, UK.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Frost
authors.forename: Musib
authors.initials: M
authors.lastname: Siddique
authors.forename: Glen M
authors.initials: GM
authors.lastname: Blake
authors.forename: Amelia E B
authors.initials: AE
authors.lastname: Moore
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Schleyer
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dunn
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Somer
authors.forename: Paul K
authors.initials: PK
authors.lastname: Marsden
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Ignac
authors.initials: I
authors.lastname: Fogelman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D003710:Demography; D005260:Female; D005459:Fluorides / Q000097:blood / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D006801:Humans; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D049268:Positron-Emission Tomography; D018709:Statistics, Nonparametric; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D005462:Fluorine Radioisotopes; D019379:Teriparatide; D005459:Fluorides