Abstract
Summary
These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation and therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans.
Introduction
Stimulation of bone formation by PTH is known to, in part, act via increased mechanosensitivity. Therefore, unloading should decrease the response to PTH treatment in uninjured bone. This has served as a background for speculations that PTH might be less efficacious for human fracture treatment in unloaded limbs, e.g. for distal radial fractures. We analyzed if the connection with mechanical stimulation also pertains to bone formation after trauma in cancellous bone.
Methods
20 male SD rats, 8 weeks old, had one hind leg immobilised via Botox injections. At 10 weeks of age the rats received bilateral screw implants into their proximal tibiae. Half of the rats were given daily injections of 5µg/kg PTH(1–34). After two weeks of healing, the tibias and femurs were harvested. Mechanical testing of screw fixation (pull-out) and µCT of the cancellous bone of the distal femurs was performed.
Results
The pull-out forces served as a read-out for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded (from 30 to 44 N). These force values are not limited by a ceiling effect, and the difference in relative effect of PTH was significant (p = 0.03).
Discussion/Conclusion
PTH appeared to exert a greater effect on bone healing in the unloaded limbs, compensating for the lack of mechanical stimulation. These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation. Therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans.
