Abstract: Objective To establish an animal model of chronic pancreatitis-induced osteoporosis and to investigate the effects of chronic pancreatitis (CP) on bone loss in mice and the underlying mechanism. Methods Forty Kunming (KM) mice aged 6-8 weeks were divided into control group (n=20) and CP group (n=20). The CP mouse model was established by intraperitoneal injection of L-arginine, while the control group received an equal volume of normal saline. Samples were collected at 8 and 12 weeks after modeling. Pathological changes in the pancreas were observed by HE staining and Masson staining. Bone quality and bone morphology were assessed by micro-CT and HE staining. The expression of bone formation markers OPN and Runx2 proteins was detected by immunohisto- chemical staining. Levels of fecal elastase-1, serum vitamin D, Ca²⁺, and osteocalcin were measured by ELISA. Results At 8 weeks after modeling, compared with the control group, the CP group showed atrophy and necrosis of the pancreatic parenchyma, accompanied by extensive inflammatory cell infiltration and increased fibrosis; decreased trabecular bone density in the femur and tibia, significant destruction of bone microstructure, and reduced overall bone mass (P＜0.05); and significantly decreased expression of bone formation markers OPN and Runx2 proteins in bone tissue (P＜0.05). The CP group also exhibited significantly lower levels of fecal elastase-1, serum vitamin D, Ca²⁺, and osteocalcin (P＜0.05). These changes became more significant with the extension of modeling duration to 12 weeks. Conclusions Intraperitoneal injection of L-arginine successfully establishes a mouse model of chronic pancreatitis-induced osteoporosis. The pathological mechanism is associated with impaired vitamin D absorption leading to reduced bone formation.

Key words: chronic pancreatitis, osteoporosis, bone formation, animal model