title: Combined treatment with PTH (1-34) and OPG increases bone volume and uniformity of mineralization in aged ovariectomized rats.
abstract: The combination of PTH with OPG has been proposed as a potential therapy in patients with severe osteoporosis. In the present study, we examined the bone material of aged ovariectomized (OVX) rats treated either with PTH (1-34) or OPG alone or in combination of both. The micro- and nanostructural characteristics of the mineralized bone were evaluated using quantitative backscattered electron imaging (qBEI) and small-angle X-ray scattering (SAXS). Rats (n=68) were either sham-operated or ovariectomized (OVX) at the age of 3 months, and 15 months later, OVX animals were treated either with vehicle, OPG (10 mg/kg), PTH (80 microg/kg) or a combination of both during 5.5 months. All treatments were by subcutaneous injection, 3 days per week. Secondary metaphyseal spongiosa from distal femora was assessed for mineralized bone volume (BV/TV), for the mean Ca-concentration (Camean), the width of the bone mineralization density distribution (Cawidth), as well as the average mineral particle thickness parameter (T) and the degree of alignment of the mineral particles (rho). A remarkable increase of BV/TV up to 139% (P<0.001) was observed in the PTH-treated groups independently of OPG. Camean was slightly increased (+1.7%, P<0.05) in the OPG-treated group. Cawidth was reduced (-6.4%, P<0.01, and -8.9%, P<0.001) in animals treated with OPG and PTH+OPG, respectively. In contrast, Cawidth in sham-operated rats was 16.0% (P<0.001) higher than in OVX. The T parameter was not altered in the trabecular bone within the group of treated and untreated OVX rats. However, the non-ovariectomized animals exhibited a significantly lower T value (-7.1%, P<0.01) with respect to OVX. In conclusion, qBEI and SAXS data of OVX rats suggest that PTH alone was responsible for increase of bone volume, whereas OPG positively influenced the homogeneity and density of mineralization without affecting the nanostructure of the bone material.
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital Heinrich Collin Str. 30 A-1140 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Valenta
authors.forename: P
authors.initials: P
authors.lastname: Roschger
authors.forename: N
authors.initials: N
authors.lastname: Fratzl-Zelman
authors.forename: P J
authors.initials: PJ
authors.lastname: Kostenuik
authors.forename: C R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: P
authors.initials: P
authors.lastname: Fratzl
authors.forename: K
authors.initials: K
authors.lastname: Klaushofer
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D004359:Drug Therapy, Combination; D004577:Electron Probe Microanalysis; D005269:Femur / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008903:Minerals / Q000032:analysis / Q000737:chemistry; D010024:Osteoporosis / Q000188:drug therapy; D053244:Osteoprotegerin; D010052:Ovariectomy; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D019379:Teriparatide / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D006023:Glycoproteins; D008903:Minerals; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506032:Tnfrsf11b protein, rat; D019379:Teriparatide; D002118:Calcium