Optimal intermittent administration interval of parathyroid hormone 1‐34 for bone morphogenetic protein‐induced bone formation in a rat spinal fusion model

Introduction Both bone morphogenetic protein 2 (BMP‐2) and teriparatide (parathyroid hormone [PTH] 1‐34) are used to enhance bone healing. There is still no established opinion regarding the optimum dose and administration method. We investigated the optimal administration method for the combination of BMP‐2 and PTH 1‐34 in a rat spinal fusion model. Methods Group I was implanted with a control carrier. Groups II, III, and IV were implanted with a carrier containing 3 μg of recombinant human BMP‐2 (rhBMP‐2). In addition, following implantation, PTH 1‐34 injections were administered to Group III thrice a week (total, 180 μg/kg/week) and Group IV six times a week (total, 180 μg/kg/week). The rats were euthanized after 8 weeks, and their spines were explanted; assessed by manual palpation, radiographs, and high‐resolution micro‐computed tomography (micro‐CT); and subjected to histological analysis. Serum markers of bone metabolism were also analyzed. Results Manual palpation tests showed that the fusion rates in Groups III and IV were considerably higher than those in Group I. They also had higher radiographic scores than Group I and II. Micro‐CT analysis revealed Tb.Th in the Group IV had higher values than that in the Group I, II, III with significant differences and Tb.Sp in the Group IV had lower values than that in the Group I, II, III with significant differences. Serum marker analysis revealed that Group IV had higher osteocalcin and lower tartrate‐resistant acid phosphatase‐5b than Group III. Histological analysis indicated that Group IV had enhanced trabecular bone structure. Conclusions Frequent administration of PTH may be better in making thicker and strengthening the trabecular bone structure in newly formed bone in the rat spinal fusion model using insufficient BMP‐2.

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