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Home / Equine Research Bank / Bone Joint Res / Increased sclerostin associated with stress fracture of the ...
Bone & joint research2018; 7(1); 94-102; doi: 10.1302/2046-3758.71.BJR-2016-0202.R4

Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse.

Abstract: The exact aetiology and pathogenesis of microdamage-induced long bone fractures remain unknown. These fractures are likely to be the result of inadequate bone remodelling in response to damage. This study aims to identify an association of osteocyte apoptosis, the presence of osteocytic osteolysis, and any alterations in sclerostin expression with a fracture of the third metacarpal (Mc-III) bone of Thoroughbred racehorses. Methods: A total of 30 Mc-III bones were obtained; ten bones were fractured during racing, ten were from the contralateral limb, and ten were from control horses. Each Mc-III bone was divided into a fracture site, condyle, condylar groove, and sagittal ridge. Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were measured using TUNEL staining. Cathepsin K, matrix metalloproteinase-13 (MMP-13), HtrA1, and sclerostin expression were analyzed. Results: In the fracture group, microdamage was elevated 38.9% (sd 2.6) compared with controls. There was no difference in the osteocyte number and the percentage of apoptotic cells between contralateral limb and unraced control; however, there were significantly fewer apoptotic cells in fractured samples (p < 0.02). Immunohistochemistry showed that in deep zones of the fractured samples, sclerostin expression was significantly higher (p < 0.03) than the total number of osteocytes. No increase in cathepsin K, MMP-13, or HtrA1 was present. Conclusions: There is increased microdamage in Mc-III bones that have fractured during racing. In this study, this is not associated with osteocyte apoptosis or osteocytic osteolysis. The finding of increased sclerostin in the region of the fracture suggests that this protein may be playing a key role in the regulation of bone microdamage during stress adaptation. 2018;7:94-102.
© 2018 Hopper et al.
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Publication Date: 2018-01-25 PubMed ID: 29363519PubMed Central: PMC5805827DOI: 10.1302/2046-3758.71.BJR-2016-0202.R4Google Scholar: Lookup
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Summary

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This study investigates the causes of microdamage-induced long bone fractures in Thoroughbred racehorses, focusing on the third metacarpal bone. The research reveals a significant increase in a protein called sclerostin in the area of the fracture, suggesting its key role in managing bone microdamage during stress response.

Approach and Methods

  • The research involved an analysis of 30 third metacarpal (Mc-III) bones sourced from several types of horses. The first group included bones that had fractured during racing, the second group comprised bones from the unfractured side of the same horses and the third was a control group from control horses.
  • Each bone was divided into four parts – the fracture site, the condylar groove, the condyle, and the sagittal ridge. Then microcracks and other diffuse microdamage were quantitatively examined.
  • A test called TUNEL staining was used to measure the rate of apoptotic (self-destructing) osteocytes (bone cells).
  • The study looked at the expression of four molecules: sclerostin, HtrA1, cathepsin K, and matrix metalloproteinase-13 (MMP-13) in each bone sample.

Key Findings

  • The research revealed that microdamage was considerably higher (by 38.9%) in fractured bones compared to control ones.
  • No significant difference was found in the number of osteocytes and apoptotic cells between the unfractured limb and the control group. Interestingly, there were significantly fewer apoptotic cells in the fractured samples.
  • Immunohistochemistry tests showed an increase in the expression of sclerostin in deeper parts of the fractured samples, significantly higher than the total number of osteocytes.
  • However, there was no increase detected in the presence of the other three molecules – cathepsin K, MMP-13, and HtrA1.

Conclusion

  • The study concluded that there is a noticeable increase in microdamage in Mc-III bones that have fractured during racing.
  • The research demonstrated that sclerostin, a protein known for its role in bone formation and remodelling, may be a key factor in regulating such bone microdamage during high stress periods like racing.
  • The absence of a comparable increase in cell apoptosis or osteocytic osteolysis demonstrates that these factors are not significantly associated with the observed fractures.

Cite This Article

APA
Hopper N, Singer E, Henson F. (2018). Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred racehorse. Bone Joint Res, 7(1), 94-102. https://doi.org/10.1302/2046-3758.71.BJR-2016-0202.R4

Publication

Bone & joint research
ISSN: 2046-3758
NlmUniqueID: 101586057
Country: England
Language: English
Volume: 7
Issue: 1
Pages: 94-102

Researcher Affiliations

Hopper, N
  • Department of Surgery, University of Cambridge niina.hopper@gmail.com.
Singer, E
  • Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, School of Veterinary Medicine, Leahurst, Chester High Road, Neston CH64 6SW, UK.
Henson, F
  • Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK and Division of Trauma and Orthopaedic Surgery, University of Cambridge, Hills Road, Cambridge BC2 0QQ, UK.

Conflict of Interest Statement

Conflicts of Interest Statement: None declared

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