| Sclerostin antibody is being developed for the treatment of postmenopausal osteoporosis because of its robust efficacy in increasing bone volume. Generally, sclerostin, the protein product of the SOST gene, maintains bone surfaces quiescent. Neutralizing sclerostin with an antibody up-regulates Wnt signaling and activates quiescent surfaces into bone forming surfaces. While studies show that antibody treatment in animals and humans increases bone volume, little data has been published describing the quality of the newly formed bone. We hypothesize that treatment with sclerostin antibody will lead to a short-term depression in overall bone mineralization because of the anticipated increase in bone volume and the lag time associated with full mineralization. In the present experiment, the femurs of 30 Sprague Dawley rats that had received titanium implants in their contralateral limbs were used. The rats were treated with saline or sclerostin antibody (Scl-Ab III: 25mg/kg, twice weekly) for 2, 4 or 8 weeks. Positive effects of sclerostin antibody treatment on implant fixation were reported previously. In the present investigation, the intact femurs were harvested, formalin-fixed and scanned using micro-computed tomography (microCT) to assess bone volume and mineral tomography (microCT) to assess bone volume and mineral density. The bones were then embedded in polymethyl methacrylate, sectioned, polished, carbon-coated and imaged using quantitative backscatter electron imaging (qBEI) as a second assessment of mineral density. Both microCT and qBEI confirmed increases in bone volume: in trabecular bone, when 8 week controls and treated samples were compared, microCT noted a 3-fold increase in trabecular BV/TV (p<.00I), while qBEI noted an increase in trabecular BV/TV of 29% (p=.008). In cortical bone area, microCT noted an increase of 29% (p=0.001) and qBEI noted an increase of 19% (p=.033). qBEI also noted statistically significant increases in trabecular bone volume by as early as 2 weeks (p=.025). Contrary to our hypothesis however, the mineral density of the cortical and trabecular bone, whether assayed by microCT or qBEI showed no statistical difference between treated and untreated groups at 2, 4 and 8 weeks. The standard deviation, skewness and kurtosis of the mineral frequency distributions were also similar between groups. Although an interesting finding, additional studies need to be performed before the affect of sclerostin antibody on mineralization is fully elucidated. |
