Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven.
OBJECTIVE
Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats.


METHODS
Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD.


RESULTS
HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density.


CONCLUSIONS
HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats.
Department of Medicine III, Dresden Technical University Medical Center, Dresden, Germany. Electronic address: martina.rauner@uniklinikum-dresden.de.
Martina
M
Rauner
Department of Medicine III, Dresden Technical University Medical Center, Dresden, Germany.
Sylvia
S
Thiele
Institut Cochin, Hôpital Cochin, Paris, France.
Ingrid
I
Fert
Institut Cochin, Hôpital Cochin, Paris, France.
Luiza M
LM
Araujo
Pediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD, USA.
Gerlinde
G
Layh-Schmitt
Pediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD, USA.
Robert A
RA
Colbert
Department of Orthopedics, Dresden Technical University Medical Center, Dresden, Germany.
Christine
C
Hofbauer
Max Bergmann Center of Biomaterials, Technical University, Dresden, Germany.
Ricardo
R
Bernhardt
Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland.
Alexander
A
Bürki
Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland.
Jakob
J
Schwiedrzik
Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland.
Philippe K
PK
Zysset
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria.
Peter
P
Pietschmann
University of TX Southwestern Medical Center, Dallas, USA.
Joel D
JD
Taurog
Institut Cochin, Hôpital Cochin, Paris, France.
Maxime
M
Breban
Department of Medicine III, Dresden Technical University Medical Center, Dresden, Germany; Center for Regenerative Therapies, Dresden, Germany.
Lorenz C
LC
Hofbauer
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D010010:Osteoclasts / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D025242:Spondylarthropathies / Q000150:complications / Q000235:genetics / Q000473:pathology*; D014057:Tomography, X-Ray Computed
D015796:HLA-B27 Antigen
Bone loss; Bone remodeling; HLA-B27 transgenic rat; Inflammatory bowel disease; Spondyloarthritis