Technically, enthesopathy is the calcification of tendons and ligaments where they attach to bones (insertion points). It can happen to anyone, with XLH or not, but it happens earlier and more extensively in XLH patients. It can be extremely disabling, since it turns soft tissue (ligaments and tendons) that are supposed to be stretchy into hard, fixed substances more like stone than rubber.
As noted, it can happen to anyone, and there are other disorders than XLH where it happens early and extensively. Another chronic hypophosphatemia, GACI (Generalized Arterial Calcification of Infancy) is one, and it occurs even earlier and more catastrophically in that condition (fatal in roughly half of pediatric patients).
And yet, very little is understood about the biochemistry of enthesopathy. It’s generally been theorized that it’s a reaction to a weakness in the underlying bone. I think of it is the body troweling calcium into a weak spot, like plastering over a dent in a wall. But we don’t know for sure yet.
The one thing we do know for sure is that enthesopathy is a major cause of disability in XLH patients. Not all clinicians know that though, so if you need some evidence, I’ve got some articles for you!
The most research comes from XLH Network Scientific Advisory Board Chair, who established that in hypophosphatemic mice, “The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia.” This article is behind a paywall, so I only have access to the abstract, but your clinician might have access to the whole article (and may be better at parsing its dense scientific jargon than I am).
Dr. Macica has written about enthesopathy in XLH before, and those articles are both easier to understand and not behind a paywall. So check them out (or share them with your clinician): “Survey of the enthesopathy of X-linked hypophosphatemia and its characterization in Hyp mice” and “Mineralizing enthesopathy is a common feature of renal phosphate-wasting disorders attributed to FGF23 and is exacerbated by standard therapy in hyp mice.”
Dr. Macica is not the only researcher looking at enthesopathy in hypophosphatemic mice. There an article from a few years ago (2020) that addresses “Development of Enthesopathies and Joint Structural Damage in a Murine Model of X-Linked Hypophosphatemia.”
Wouldn’t it be great if XLH research turns out to be instrumental in understanding enthesopathy for everyone, not just us, much like XLH research led to the discovery of FGF23?
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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