Changes over time in callus formation caused by intermittently administering PTH in rabbit distraction osteogenesis models

Abstract

BackgroundChanges over time in the callus during intermittent administration of parathyroid hormone (PTH) were studied in rabbit distraction osteogenesis models.MethodModels of distraction osteogenesis in Japanese white rabbits were created, and distraction osteogenesis (total length: 10.5 mm) was performed for 2 weeks. Simultaneously with the start of distraction, 30 rabbits received 4 weeks of subcutaneous administration of 30 μg/kg of PTH(1–34), teriparatide, (P-group: n = 15) or saline (N-group: n = 15) every other day. The tibias of five rabbits were dissected at 6, 8, and 10 weeks after surgery to perform bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), and mechanical testing.ResultsThe mean BMD had no significant differences over time at 6, 8, and 10 weeks after surgery between the P-group and the N-group. On pQCT, the P-group had significant increases in total bone cross-sectional area of the callus compared to the N-group at 8 and 10 weeks after surgery. On mechanical testing, the P-group’s absorption energy had not changed at 6 weeks after surgery compared to the N-group, but it had significantly increased at 8 weeks. At 10 weeks after surgery, the N-group’s absorption energy rapidly increased, and the difference between the two groups disappeared.ConclusionThe intermittent administration of PTH(1–34), teriparatide, for 4 weeks every other day from the start of distraction had the potential to shorten the callus maturation period in the rabbit distraction osteogenesis models.

Locally administrated single-dose teriparatide affects critical-size rabbit calvarial defects: A histological, histomorphometric and micro-CT study

“…In recent years, systemic treatment by the administration of rhPTH at daily intervals has been shown to improve bone healing in calvarial defects in rats,14, 15 implants placed in the tibia,4, 16 periodontal defects, 17 and distraction osteogenesis in rabbits 18, 19. However, the effects of local administration of rhPTH have not been completely evaluated.…”

“…PTH is a polypeptide hormone consisting of 84 amino acids and exerts its biological effect via the 1-34 segment on the N-terminus region. This functional segment, known as rhPTH, has been shown to increase total bone mass by accelerating bone formation 18 . Systemic administration of rhPTH at daily intervals on spongy bone is thought to improve and strengthen the bone microstructure; it has been shown to exert this effect by increasing the connection between cortical and spongy bone and changing the structure of the trabeculae from a rod-like to a plate-like form 23 .…”

“…Many animal studies from fracture healing models to implant osteointegration models have demonstrated the positive effect of systemic administration of rhPTH at intervals on bone healing 18, 29. However, there are very few studies on the effect of a single dose of rhPTH administered locally during surgery.…”

Parathyroid Hormone (1-34) Might Not Improve Early Bone Healing after Sinus Augmentation in Healthy Rabbits

“…Data on the osteoanabolic effects of intermittent PTH in animal studies are accumulating [ 4 ]. When reviewing studies limited to rabbits, most studies have found positive effects of intermittent PTH on implant osteogenesis [ 11 , 31 , 34 ] and distraction osteogenesis [ 18 , 35 ]. A search for studies involving other animals and other sites did not reveal results of intermittent PTH administration not enhancing bone healing.…”

“…The early trials involved spinal fusion surgery, with PTH showing positive effects on the survival of allografts and autografts [ 15 – 17 ]. In other animal studies, PTH stimulated distraction osteogenesis in rabbits [ 18 ] and allograft integration in calvarial bone defects in mice [ 19 ]. Animal studies related to dental effects found that PTH stimulated healing after bone graft on extraction sockets [ 20 ] and calvarial bone autografts on the mandible in rats [ 21 ].…”