Strontium combined with bioceramics for osteoporotic bone repair: Oral intake or as a dopant?

Abstract Osteoporotic bone defect repair using synthetic biomaterial-based strategies is promising but remains challenging as it requires superior efficient osteogenic effects. Due to the strong osteogenic potential of strontium (Sr), there is a growing interest in modifying inorganic porous scaffolds by incorporating Sr or combining the scaffold with strontium ranelate (SrRAN) drug administration. To compare the therapeutic effect of these two approaches, critical-sized bone defects were repaired using pure hydroxyapatite bioceramics (HA group), Sr-doped HA (SrHA group), or pure HA combined SrRAN drug oral intake (SrRAN+HA group). After 8 and 12 weeks of implantation, micro-CT analysis revealed excellent bone formation in the SrRAN+HA group compared to the SrHA group in terms of a significantly higher bone volume ratio within the defect (dBV/TV). With regard to the new bone volume ratio at the periphery of the defect (pBV/TV), the values of SrHA and SrRAN+HA in a peri-implant 500-μm region at week 12 were comparable. Furthermore, a histological analysis demonstrated that the implant and the host bone were tightly connected without any gaps in the SrRAN+HA group after week 8. In addition, SrRAN+HA expressed more Emcn/CD31 double-positive vessels and OCN protein than the SrHA group. Finally, we discovered that SrHA substantially increased the Sr concentration in the surrounding bone tissue, but no improvement in the mechanical properties was observed. Our findings indicated that, compare to Sr-dopant, implantation of bioceramics with SrRAN systematic treatment would be a more efficient method to increase new bone formation and osteointegration in critical-sized osteoporotic bone defects.