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Intervertebral disc is an alternate tissue source of circulating C-telopeptide of type II collagen after menopause or ovariectomy: Comment on the article by Sondergaard et al

Cake, M.ORCID: 0000-0002-0072-9024 and Melrose, J. (2008) Intervertebral disc is an alternate tissue source of circulating C-telopeptide of type II collagen after menopause or ovariectomy: Comment on the article by Sondergaard et al. Arthritis & Rheumatism, 58 (5). p. 1560.

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To the Editor:

We write to caution against the now routine presumption, recently repeated in this journal by Sondergaard and coworkers (1), that circulating levels of C-telopeptide of type II collagen (CTX-II) represent a direct surrogate measure of articular cartilage degradation, particularly after menopause or ovariectomy. A growing body of research suggests that intervertebral discs (IVDs) also represent a likely source of CTX-II following either natural or surgical menopause. The evidence for this is as follows.

First, articular cartilage is but one tissue pool of type II collagen in the body. One canine dissection study estimated that articular cartilage and IVD represent 0.06% and 0.10% of dry body weight, respectively, both of which were dwarfed by other extraarticular cartilage pools (2). Second, IVD is an estrogen-responsive tissue. Human IVD cells express estrogen receptor β and respond to exogenous estradiol in vitro (3). Third, several studies have demonstrated narrowing of IVD height in postmenopausal women compared with premenopausal or hormone-treated women (4, 5), and that this narrowing is rapidly progressive in the period immediately following menopause (5), suggestive of rapid tissue remodeling, if not frank IVD degeneration. Fourth, animal studies confirm IVD changes following surgical ovariectomy, notably in rats, which show a significant (2–3-fold) increase in lumbar disc pathology, apoptosis of nucleus pulposus cells, and up-regulation of the pathological mediator inducible nitric oxide synthase following ovariectomy (6, 7). Our own research group has also demonstrated altered IVD biomechanical function in ovariectomized ewes 6 months after ovariectomy (Cake M et al: unpublished observations).

Furthermore, a link between elevated CTX-II levels and IVD disease has been directly demonstrated by Garnero et al (8), who showed by multivariate analysis that the contribution of lumbar disc space narrowing to circulating CTX-II levels was similar to, and independent of, the contribution of radiologic knee osteoarthritis or clinical hand osteoarthritis. This finding, combined with the above evidence from both human and animal studies of IVD narrowing, remodeling, and/or degeneration following menopause or ovariectomy, indicates that IVD is indeed a potential source of circulating CTX-II in these conditions, and that, as indeed the above-cited work (1) has done, additional sources of evidence for articular cartilage degradation should support claims based on measurement of serum or urinary CTX-II.

Item Type: Journal Article
Murdoch Affiliation(s): School of Veterinary and Biomedical Sciences
Publisher: Wiley-Blackwell
Copyright: 2008 American College of Rheumatology
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