Human parathyroid hormone (1–34) accelerates the fracture healing process of woven to lamellar bone replacement and new cortical shell formation in rat femora

Abstract

This study aimed to test whether intermittent treatment of human parathyroid hormone [hPTH(1–34)] disturbs or accelerates the fracture healing process using rat surgical osteotomy model. One hundred five, 5-week-old SD rats were allocated to vehicle control (CNT) and four PTH groups; 10 and 30 μg/kg of hPTH(1–34) treatment before surgery (P10, P30), and treatment before and after surgery (C10, C30). All animals were given subcutaneous injections three times a week for 3 weeks. Then, fractures were produced by transversely cutting the midshaft of bilateral femora and fixing with intramedullary wire. Human PTH(1–34) treatment was continued in C10 and C30 groups until sacrifice at 3, 6, and 12 weeks after surgery. The femora were assessed by peripheral quantitative computed tomography, three-point bending mechanical test, and histomorphometry. Total cross-sectional area was not significantly different among all groups at any time point. At 3 weeks after surgery, the lamellar bone/callus area was significantly increased in C10 and C30 groups compared to the other groups. At 6 weeks, remodeling of woven bone to lamellar bone in the callus was almost complete in all groups. At 12 weeks, percent new cortical shell area was significantly higher in C10 and C30 groups compared to the other groups, and the ultimate load in mechanical testing was significantly higher in C30 group than in CNT, P10, and P30 groups. Intermittent PTH treatment at 30 μg/kg before and after osteotomy accelerated the healing process as evidenced by earlier replacement of woven bone to lamellar bone, increased new cortical shell formation, and increased the ultimate load up to 12 weeks after osteotomy.