It is a particularly critical challenge to achieve enough bone regeneration in osteoporotic fractures with bone defects. In the present study, we designed a micro-/nano-structured calcium phosphate bioceramic composed of a nanoparticle-reinforced micro-whisker backbone (nwCaP). This sandwich-structured bioceramic exhibited a higher compressive strength, a suitable degradation rate and better cell attachment than traditional or intermediate bioceramics. In a rat model of osteoporotic bone defects, the nwCaP group showed a reduced fracture occurrence and an effective new bone substitution rate, as characterized by micro-CT analysis. The increased bone formation rate and greater amount of new bone formed within the defected area of the nwCaP group was revealed by the serum PINP level and histological staining. Moreover, a gene microarray study indicated that the promotion of osteogenesis might be attributed to selectively upregulated fibroblast growth factor 23 (FGF23) expression in cells co-cultured with the nwCaP bioceramic. Furthermore, the JAK2 signal pathway was confirmed to be involved in the nwCaP-induced elevation of FGF23 expression using primary osteoblasts derived from osteoporotic rats. Collectively, the findings suggested that the micro-/nano-structured bioceramic could enhance osteoporotic bone regeneration and presents a promising strategy for healing bone defects in osteoporosis.