Doses effects of zoledronic acid on mineral apatite and collagen quality of newly-formed bone in the rat's calvaria defect

- Zoledronic acid (ZA) acid affects the bone quality during bone formation in a craniofacial defect rat model
- The cristallinity is lowered in newly-formed bone with high ZA dose
- The hydroxyproline-to-proline ratio, an indicator of the collagen stability, is lowered in newly-formed bone with high ZA dose
- Contrarily to high ZA dose, newly-formed bone is not modified neither by single nor fractionated low ZA doses
- The cristallinity is positively correlated with the hydroxyproline-to-proline ratio in the newly-formed bone

Due to their inhibitory effects on resorption, bisphosphonates are widely used in the treatment of diseases associated to an extensive bone loss. Yet, little is known about bisphosphonates effects on newly-formed bone quality. In the present study, adult male Sprague-Dawley rats (n = 80) with a bone defect calvaria area were used and short-term effects of zoledronic acid (ZA) were studied on the healing bone area. Three ZA treatments were tested by using either: 1°) a low single dose (120 μg ZA/kg, n = 10; equivalent to human osteoporosis treatment), 2°) a low fractionated doses (20 μg ZA/kg daily for 6 days either a total of 120 μg/kg, n = 15), and 3°) a high fractionated doses, (100 μg ZA/kg weekly for 6 weeks, n = 15; equivalent to 6 months of human bone metastasis treatment). For each treatment, a control “vehicle” treatment was performed (with an identical number of rats). After ZA administration, the intrinsic bone material properties were evaluated by quantitative backscattered electron imaging (qBEI) and Raman microspectroscopy. Neither single nor fractionated low ZA doses modify the intrinsic bone material properties of the newly-formed bone compared to their respective control animals. On the opposite, the high ZA treatment resulted in a significant decrease of the crystallinity (− 25%, P < 0.05) and of the hydroxyproline-to-proline ratio (− 30%, P < 0.05) in newly-formed bones. Moreover, with the high ZA treatment, the crystallinity was positively correlated with the hydroxyproline-to-proline ratio (ρ = 0.78, P < 0.0001). The present data highlight new properties for ZA on bone formation in a craniofacial defect model. As such, ZA at high doses disrupted the apatite crystal organization. In addition, we report here for the first time that high ZA doses decreased the hydroxyproline-to-proline ratio suggesting that ZA may affect the early collagen organization during the bone healing.