Parathyroid hormone PTH(1–34) increases the volume, mineral content, and mechanical properties of regenerated mineralizing tissue after distraction osteogenesis in rabbits

Abstract

Background and purpose Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. Recently, it has been suggested that PTH can also enhance bone repair after fracture and distraction osteogenesis. We analyzed bone density and strength of the newly regenerated mineralized tissue after intermittent treatment with PTH in rabbits, which undergo Haversian bone remodeling similar to that in humans.

Methods 72 New Zealand White rabbits underwent tibial mid-diaphyseal osteotomy and the callus was distracted 1 mm/day for 10 days. The rabbits were divided into 3 groups, which received injections of PTH 25 µg/kg/day for 30 days, saline for 10 days and PTH 25 µg/kg/day for 20 days, or saline for 30 days. At the end of the study, the rabbits were killed and the bone density was evaluated with DEXA. The mechanical bone strength was determined by use of a 3-point bending test.

Results In the 2 PTH-treated groups the regenerate callus ultimate load was 33% and 30% higher, absorbed energy was 100% and 65% higher, BMC was 61% and 60% higher, and callus tissue volume was 179% and 197% higher than for the control group.

Interpretation We found that treatment with PTH during distraction osteogenesis resulted in substantially higher mineralized tissue volume, mineral content, and bending strength. This suggests that treatment with PTH may benefit new bone formation during distraction osteogenesis and could form a basis for clinical application of this therapy in humans.

Acknowledgements

RA, HE, KGB, ML, and IH: study design, data analysis, and preparation of manuscript. RA, HE, and KGB: operation of animals. JST: mechanical testing, data analysis, and preparation of manuscript. RA: densitometry.

We thank Henrik Barlebo, MD, and animal caretakers Torben Madsen, Jens Sørensen, and Ole Sørensen at the animal laboratory of the Institute of Pathology, Aalborg Hospital, University of Aarhus for their technical assistance and support during the animal experiment. Anne Arveschoug is acknowledged for help with DEXA measurements at the Department of Nuclear Medicine, Aalborg Hospital, University of Aarhus, and we are grateful to laboratory technicians Anette Milton and Jane Pauli for their assistance during preparation of the bone samples at the Orthopaedic Surgery Research Laboratory, University of Aarhus. We thank Merete Fischer, Institute of Anatomy, University of Aarhus, for linguistic revision of the manuscript.

This study was financially supported by Aarhus University Research Foundation, the Gangste Foundation, the Helga and Peter Korning Foundation, the Obel Family Foundation, the Herta Christensen Foundation, the A.P. Møller Foundation, the Division of Orthopaedic Surgery in Northern Jutland, the Aarhus University Research Initiative, and by the Sahva Foundation.

No competing interests declared.

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