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Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mouse model of rheumatoid arthritis

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Abstract

Summary

This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA.

Introduction

Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA.

Methods

Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing.

Results

SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice.

Conclusions

Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.

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Abbreviations

RA:

Rheumatoid arthritis

RANKL:

Receptor activator of NF-kB ligand

SH2:

Src homology 2

ZAP-70:

ζ-associated protein of 70 kDa

CTX:

C-terminal telopeptides of type I collagen

BV/TV:

Trabecular bone volume fraction

Tb.N:

Trabecular number

Tb.Th:

Trabecular thickness

SMI:

Structural model index

Ct.Th:

Cortical thickness

FTIR:

Fourier transform infrared

PMMA:

Poly methyl methacrylate

MCT:

Mercury–cadmium–telluride

MTMR:

Mineral to matrix ratio

CTPR:

Carbonate to phosphate ratio

HAp:

Hydroxyapatite

SD:

Standard deviation

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Acknowledgments

This project was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan 25462357 (M. Takahata) and by a Grant-in-Aid for Scientific Research (A), MEXT (No. 15H02207) (S. Tadano).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    T. Shimizu, M. Takahata, Y. Kameda, K. Endo, H. Hamano, S. Hiratsuka, M. Ota, D. Sato & N. Iwasaki

  2. Chitose Institute of Science and Technology, Chitose, Japan

    H. Kimura-Suda & T. Ito

  3. Division of Human Mechanical Systems and Design, Faculty of Engineering, Hokkaido University, Sapporo, Japan

    K. Endo, M. Todoh & S. Tadano

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  1. T. Shimizu
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  2. M. Takahata
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  3. H. Kimura-Suda
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  4. Y. Kameda
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Corresponding author

Correspondence to M. Takahata.

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The Ethics Review Committee for Animal Experimentation of Hokkaido University approved the experimental protocol of this study.

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Shimizu, T., Takahata, M., Kimura-Suda, H. et al. Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mouse model of rheumatoid arthritis. Osteoporos Int 28, 709–718 (2017). https://doi.org/10.1007/s00198-016-3781-6

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  • DOI: https://doi.org/10.1007/s00198-016-3781-6

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