Combined treatment with PTH (1-34) and OPG increases bone volume and uniformity of mineralization in aged ovariectomnized rats

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 mu g/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 (Ca-mean), the width of the bone mineralization density distribution (Ca-width), as well as the average mineral particle thickness parameter (T) and the degree of alignment of the mineral particles (p). A remarkable increase of BV/TV up to 139% (P < 0.001) was observed in the PTH-treated groups independently of OPG. Ca-mean was slightly increased (+1.7%, P < 0.05) in the OPG-treated group. Ca-width was reduced (-6.4%, P < 0.01, and -8.9%, P < 0.001) in animals treated with OPG and PTH + OPG, respectively. In contrast, Ca-width 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. (C) 2005 Elsevier Inc. All rights reserved.