Dose-dependent effects of pharmaceutical treatments on bone matrix properties in ovariectomized rats

As both anabolic and anti-catabolic osteoporosis drugs affect bone formation and resorption processes, they may contribute to bone's overall mechanical behavior by altering the quality of the bone matrix. We used an ovariectomized rat model and a novel fracture mechanics approach to investigate whether treatment with an anabolic (parathyroid hormone) or anti-catabolic (alendronate) osteoporosis drugs will alter the organic and mineral matrix components and consequently cortical bone fracture toughness. Ovariectomized (at 5 months age) rats were treated with either parathyroid hormone or alendronate at low and high doses for 6 months (age 6-12 months). Specifically, treatment groups included untreated ovariectomized controls (n = 9), high-dose alendronate (n = 10), low-dose alendronate (n = 9), high-dose parathyroid hormone (n = 10), and low-dose parathyroid hormone (n = 9). After euthanasia, cortical microbeams from the lateral quadrant were extracted, notched, and tested in 3-point bending to measure fracture toughness. Portions of the bone were used to measure changes in the 1) organic matrix through quantification of advanced glycation end-products (AGEs) and non-collagenous proteins, and 2) mineral matrix through assessment of mineral crystallinity. Compared to the ovariectomized group, rats treated with high doses of parathyroid hormone and alendronate had significantly increased cortical bone fracture toughness, which corresponded primarily to increased non-collagenous proteins while there was no change in AGEs. Additionally, low-dose PTH treatment increased matrix crystallinity and decreased AGE levels. In summary, ovariectomized rats treated with pharmaceutical drugs had increased noncollagenous matrix proteins and improved fracture toughness compared to controls. Further investigation is required for different doses and longer treatment periods.