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Bone, not cartilage, should be the major focus in osteoarthritis

Nature Clinical Practice Rheumatology volume 3, pages 306–307 (2007)Cite this article

The importance of bone in osteoarthritis (OA) has been neglected. The main emphasis of research has been the delineation of the articular cartilage degradation mechanism, and bone changes have been generally accepted as secondary to these changes in the cartilage. The potential importance of bone in the development of OA was initially shown by Radin and others, who set the hypothesis that the increasingly thickened and stiffened subchondral bone results in damage to the articular cartilage during repetitive loading. Further impetus was provided by the demonstration that binding of technetium-labelled bisphosphonate to bone mineral correlates with progression of OA (as measured by joint space narrowing),1 which indicates a change in the OA activity of the bone.

Examination of the subchondral bone collagen of femoral heads in humans with OA has now revealed a twenty-fold increase in collagen turnover (as determined by rates of synthesis and degradation), a five-fold increase in transforming growth factor beta (TGFβ) levels, and reduced mineralization, compared with age-matched individuals without OA.2 Further analysis of the newly formed collagen has revealed an overall increase in lysine hydroxylation, caused by increased activity of the three isoforms of lysyl hydroxylase. An increase in the hydroxylation of the triple helical lysines results in the formation of narrow fibres; however, an increase in the hydroxylation of the terminal lysines changes the intermolecular cross-link profile from pyrrole to pyridinoline.3 We have shown that the pyrrole (rather than the pyridinoline) cross-link correlates with the tensile strength of compact bone.3 These changes in fibre diameter, hypo-mineralization and the presence of type I homotrimer4 are consistent with the reported reduction in strength and stiffness of bone by mechanical testing. The question arises, therefore, as to what initiates the formation of the excess new subchondral bone collagen. The abnormal presence of increased levels of TGFβ and insulin-like growth factor (IGF)-1 and 2, interleukin (IL)-1 and IL-6, prostaglandin H2 (PGE2),5 all important regulators of matrix turnover, are certainly involved; however, the question remains as to what stimulates the increased production of these factors.

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Authors and Affiliations

  1. JP Mansell is Director of Postgraduate Studies in the Department of Oral and Dental Science, C Collins is Consultant Senior Lecturer in the Department of Pathology and Microbiology and AJ Bailey is Emeritus Professor of Biochemistry in the Collagen Research Group at the University of Bristol, UK.,

    Jason P Mansell, Chris Collins & Allen J Bailey

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  1. Jason P Mansell
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  2. Chris Collins
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  3. Allen J Bailey
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Correspondence to Allen J Bailey.

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Mansell, J., Collins, C. & Bailey, A. Bone, not cartilage, should be the major focus in osteoarthritis. Nat Rev Rheumatol 3, 306–307 (2007). https://doi.org/10.1038/ncprheum0505

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