Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Max D Kauther,Gero Hilken,Martina Broecker-Preuss,Florian Grabellus,Hagen S Bachmann,Gabriele Koehler,Marius Von Knoch,Christian Wedemeyer,Laura Neuerburg

doi:10.1186/1471-2474-12-186

Abstract

BackgroundPeriprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice.MethodsWe used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.ResultsBone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.ConclusionsAs anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

Highlights

Periprosthetic osteolysis is known to be a major cause of aseptic loosening in joint arthroplasty [1]
Hoff et al stated that “the absence of the CT/calcitonin gene-related peptide (CGRP) gene is associated with increased bone formation in the basal state, and in a condition characterized by increased osteoclastic resorption” [20]
Both alphaCGRP and calcitonin are generated by alternative splicing from the Calca gene, we were interested in the outstanding phenotype of Calca deficient mice with an increased bone formation rate (BFR) in contrast to the decreased BFR in alpha-CGRP knockout mice [20,28]

Summary

Introduction

Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. Periprosthetic osteolysis is known to be a major cause of aseptic loosening in joint arthroplasty [1] This process is mainly mediated by wear particles that stimulate an inflammatory response in the surrounding tissue, leading to implant loosening. Salmon CT is preferred as a therapeutic agent against Paget’s disease and osteoporosis because of its ability to slow down bone resorption by inhibiting osteoclast activity, even though calcitonin is not widely used to treat osteoporosis[15,16,17]. Hoff et al stated that “the absence of the CT/CGRP gene is associated with increased bone formation in the basal state, and in a condition characterized by increased osteoclastic resorption” [20] They described an unexpected phenotype of high bone mass in Calca deficiency that was contrary to the expected effects of both alpha-CGRP and CT [20]. This study investigates the impact of CT deficiency and CT substitution on particle-induced osteolysis

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Results

Discussion

Conclusion