Bencaosome [16:0 Lyso PA+XLGB28‐sRNA] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice

Abstract Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti‐osteoporosis agents is limited because of their serious side effects or the high cost of long‐term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28‐sRNA targeting TNFSF11 exerted a significant anti‐osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28‐sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28‐sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.