title: Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT.
abstract: Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to detail effects on compartmental geometry, density, and microarchitecture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 µg sc daily, n = 18) or PTH 1-84 (100 µg sc daily, n = 20) for 18 months in an open-label, nonrandomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n = 33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32 ± 37%, PTH 1-84 39 ± 32%, both p < 0.001) and tibia (PTH 1-34 13 ± 27%, PTH 1-84 15 ± 22%, both p < 0.001) with corresponding declines in cortical density. With PTH 1-34, increases in cortical thickness in radius (2.0 ± 3.8%, p < 0.05) and tibia (3.8 ± 10.4%, p < 0.01) were found. Trabecular number increased in tibia with both PTH 1-34 (4.2 ± 7.1%, p < 0.05) and PTH 1-84 (5.3 ± 8.3%, p < 0.01). Zoledronic acid did not impact cortical porosity at either site but increased cortical thickness (3.0 ± 3.5%, p < 0.01), total (2.7 ± 2.5%, p < 0.001) and cortical density (1.5 ± 2.0%, p < 0.01) in tibia as well as trabecular volume fraction in radius (2.5 ± 5.1%, p < 0.05) and tibia (2.2 ± 2.2%, p < 0.01). FE estimated bone strength was preserved, but not increased, with PTH 1-34 and zoledronic acid at both sites, whereas it decreased with PTH 1-84 in radius (-2.8 ± 5.8%, p < 0.05) and tibia (-3.9 ± 4.8%, p < 0.001). Conclusively, divergent treatment-specific effects in cortical and trabecular bone were observed with anabolic and zoledronic acid therapy. The finding of decreased estimated strength with PTH 1-84 treatment was surprising and warrants confirmation.
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark. sthansen@dadlnet.dk
authors.forename: Stinus
authors.initials: S
authors.lastname: Hansen
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Hauge
authors.forename: Jens-Erik
authors.initials: JE
authors.lastname: Beck Jensen
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D010024:Osteoporosis / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D017698:Postmenopause; D011884:Radius / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013977:Tibia / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D010281:Parathyroid Hormone; D000077211:Zoledronic Acid