Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia

Cooper, David M. L.<sup>1</sup>; Harrison, Kim D.<sup>1</sup>; Hiebert, Beverly D.<sup>2</sup>; King, Gavin A.<sup>1</sup>; Panahifar, Arash<sup>3,4</sup>; Zhu, Ning<sup>3</sup>; Swekla, Kurtis J.<sup>5</sup>; Pivonka, Peter<sup>6</sup>; Chapman, L. Dean<sup>1</sup>; Arnason, Terra<sup>7</sup>

Affiliations

¹Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

²Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

³BioMedical Imaging and Therapy Beamline, Canadian Light Source, Saskatoon, Saskatchewan, Canada

⁴Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

⁵Animal Care and Research Support Office, Office of the Vice-President of Research, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

⁶School of Mechanical, Medical, and Process Engineering, Queensland University of Technology, Brisbane, Australia

⁷Department of Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Abstract and keywords

Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1–34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER). Two groups (n = 7 each) of six-month old female New Zealand white rabbits were both administered 30 μg/kg of PTH once daily for a period of two weeks to induce remodeling. Their distal right tibiae were then imaged in vivo by in-line phase contrast micro-CT at the Canadian Light Source synchrotron. Over the following two weeks the first group (PTH) received continued daily PTH while the second withdrawal group (PTHW) was administrated 0.9 % saline. At four weeks all animals were euthanized, their distal tibiae were imaged by conventional micro-CT ex vivo and histomorphometry was performed. Matching micro-CT datasets (in vivo and ex vivo) were co-registered in 3D and LER was measured from 612 BMUs. Counter to our hypothesis, mean LER was lower (p < 0.001) in the PTH group (30.19 ± 3.01 μm/day) versus the PTHW group (37.20 ± 2.77 μm/day). Despite the difference in LER, osteonal mineral apposition rate (On.MAR) did not differ between groups indicating the anabolic effect of PTH was sustained after withdrawal. The slowing of BMU progression by PTH warrants further investigation; slowed resorption combined with elevated bone formation rate, may play an important role in how PTH enhances coupling between resorption and formation within the BMU. Finally, the prolonged anabolic response following withdrawal may have utility in terms of optimizing clinical dosing regimens.

Keywords: Bone; Osteoporosis; Remodeling; μCT; Preclinical studies

Links

DOI: 10.1016/j.bone.2023.116864

PubMed: 37574096

WoS: 001066353600001

History

Received: 2023-06-9

Revised: 2023-07-19

Accepted: 2023-08-1

Online: 2023-08-11

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