Bone-Healing Pattern on Critical-Sized Defects Treated by rhPTH

Intermittent Recombinant Human Parathyroid Hormone (rhPTH 1-34) is an effective treatment for improving bone mass in patients with osteoporosis; however, its effects on bone regeneration are still unclear. The objective of this study was to evaluate the potential toxicity systemic rhPTH, as well as its ability to regenerate critical-sized defects (CZD) in bone. We used 43 female Wistar rats (body weight, 150 +/- 50 g). Critical-sized bone defects in rat calvaria received vehicle alone (Control Group, CG) or daily rhPTH (20 mu g/Kg/day) by subcutaneous injection (Experimental Group, EG). We evaluated bone healing obtained at the 1st, 3rd, and 6th wks post-surgery by biochemical, soft x-ray, histological, and morphometric studies. In the EG, at the 1st and 3rd wks, many areas of focal osteoblast hyperplasia were found on parietal bone. At the 3rd wk, woven and/or lamellar bone, in an organized interconnected trabecular network, showed disrupted mineralization. At the 6th wk, looped bone was found to have formed patterns on parietal bone. New bone formed in the EG showed significant statistical differences (p = 0.023) at the 6th wk. Systemic rhPTH at the dose of 20 mu g/Kg/day was able to stimulate bone formation on rat CZD. Also, pre-existing and new bone showed non-proliferative forms of bone hyperostosis (increased non-neoplastic bone).