Strong effect of PTH (1-34) on regenerating bone: A time sequence study in rats

Abstract

This study compares the effects of parathyroid hormone (PTH) treatment on new bone formation and normal baseline remodelling in rats. To study new bone formation we used a titanium bone chamber, and to study normal remodelling we used the femur and vertebrae from the same animals. One titanium bone chamber was inserted in the proximal tibia of each of 37 rats. The rats were randomly assigned to daily injections of human PTH (1-34) 60 μg/kg) or vehicle control and killed after 2, 4 or 6 weeks. The total distance of bone growth into the chamber was slightly increased by PTH. Body weight was not affected, and there was only a minor increase in trabecular density of the vertebral and femoral cancellous bone after 6 weeks. The only dramatic effect of PTH was seen in the chambers. In the controls, a marrow cavity formed in the chamber so that the cancellous density decreased from 44% to 24%, and 11% over 2, 4 and 6 weeks. In the PTH-treated animals, a dense network of bone trabeculae was found in the entire bone chamber at all times. The cancellous density increased from 48% to 60%, and 73% at 2, 4 and 6 weeks, respectively. The results suggest that PTH treatment can reduce the development of a resorption cavity. Thus, PTH in this model had a net antiresorptive effect, probably solely because it stimulated osteoblastic activity. Even though osteoclastic activity was present throughout the PTH specimens, it was not sufficient to resorb all newly formed bone. Since PTH seemed to have a greater effect on new bone formation in the chamber than on normal bone remodeling, it might become useful for improving the incorporation of orthopedic implants and stimulating fracture repair.