The impact of leuprolide acetate-loaded calcium phosphate silicate cement to bone regeneration under osteoporotic conditions

Biomed Mater. 2021 Jun 18;16(4). doi: 10.1088/1748-605X/ac07c0.

Abstract

Osteoporosis is detrimental to the health of skeletal structure and significantly increases the risks of bone fracture. Moreover, bone regeneration is adversely impaired by increased osteoclastic activities as a result of osteoporosis. In this study, we developed a novel formulation of injectable bone cement based on calcium phosphate silicate cement (CPSC) and leuprolide acetate (LA). Several combinations of LA-CPSC bone cement were characterized and, it is found that LA could increase the setting time and compressive strength of CPSC in a concentration-dependent manner. Moreover, thein vitroresults revealed that LA-CPSC was biocompatible and able to encourage the osteoblast proliferation via the mTOR signalling pathway. Furthermore, the LA-CPSC was implanted in the osteoporotic rats to evaluate its effectiveness to repair bone fractures under the osteoporotic conditions. The biomarker study and micro-CT analyses indicated that LA-CPSC could effectively reduce the osteoclast activities and promote the bone regeneration. In conclusion, our study demonstrated that LA-CPSC injectable bone cement should be a viable solution to repair bone fractures under the osteoporotic conditions.

Keywords: bone regeneration; calcium phosphate silicate cement; leuprolide acetate; osteoclast activity; osteoporotic bone fracture.