There are so many articles being published about XLH, that I can’t keep track of them all! Did you know that if you put XLH into the search box at pubmed, there are 848 results. And that doesn’t even include related articles that are not specific to XLH, like discussions of FGF23 in general, or TIO or the autosomal hypophosphatemias. At least seventy-five of them were published in 2025, so you can see why I’m falling behind. It’s a nice problem to have, after so many years with little interest in studying chronic hypophosphatemia!
Of course, not all of the articles are particularly useful, but I’ll spare you my rants (mostly) and focus on some new and good articles from this fall.
Brand, spanking new is “Delayed diagnosis of X-linked hypophosphatemia in the absence of family history: a global unmet need.” Spontaneous XLHers and their caregivers already knew about this problem—that it’s harder to get a diagnosis if the parents don’t have XLH—but it’s good to have published data to confirm our experiences and to bring the issue to clinicians’ attention. The article concludes, “Children without a family history of XLH are diagnosed at a significantly older age than those from families known to be affected ….”
I don’t have access to this German article’s full text, but the abstract of “Skeletal dysplasias-Multidisciplinary orthopedics” concludes with this warning to orthopedists: “The close networking of orthopedics with pediatrics and other disciplines is important to enable a state-of-the-art treatment and to monitor the influences of new forms of pharmacotherapy on the musculoskeletal apparatus.” Too many orthopedic surgeons are willing to dive into the surgical aspects of rare bone disorders without understanding the underlying causes of the bone issues, which can result in unnecessary (or downright harmful) surgery.
I’m still trying to understand this article on kidney function calculations, which I believe is basically saying that there’s a better method for calculation eGFR, especially for XLH patients when we are at risk of chronic kidney disease. (Remember: our kidneys are not intrinsically defective, but the old phos/calcitriol treatment can damage our kidneys, and we are also as much at risk of CKD from all the normal causes that the general population experiences. Having XLH doesn’t protect us against kidney disease or heart disease, etc.) “Challenges in Estimating Renal Function in X-linked Hypophosphatemia.” Since I can’t really explain the article, all I can say is that if you’re at risk of CKD, it might be worth bringing this article to your clinician’s attention, so you can discuss it.
I may have mentioned this one before, but it’s one of the recently published articles on standard of care for XLH, this one focused specifically on Italy, taking into consideration the local health care systems’ requirements and limitations: “Experts’ consensus on the management and treatment of individuals with X-linked hypophosphatemia across lifespan”
You’ve probably read one of my rants about worthless case reports that just repeat what’s already known and don’t offer any new insights. Well, this one actually does have a useful insight, so I’m glad it was published: “Case Report: Increased FGF23 and new insufficiency fractures at burosumab discontinuation in X-linked hypophosphatemia” Case reports generally focus on just one patient, so it’s always possible that she had an idiosyncratic response to treatment, and you can’t really consider her outcome as data, but it does open up areas for further research, like this one does. Basically, a patient went on burosumab to deal with an insufficiency fracture (and all the usual XLH symptoms), which healed, but then she had to stop burosumab (not because it wasn’t working, but because of insurance), and, not surprisingly, she developed two new fractures. Her other symptoms also worsened drastically. The clinicians hypothesized—and remember, this is just a guess that they suggest needs to be tested scientifically—that there was a build-up of FGF23 while she was off burosumab, which resulted in an exacerbated rebound effect. There’s no way to know (yet) if that’s true, but it’s possibly the beginning of evidence that could be used whenever an insurer wants to stop treatment because of the cost. The argument can be made that stopping treatment will be bad, not only for the patient, but for the insurer that will have to pay for future additional treatment beyond what it would have been responsible for if the patient had remained on burosumab.
There are more articles, including good ones, but for now I’m going to stop after just one more, which I find really encouraging: “Treatment with Minicircle DNA Expressing a FGF23 Fragment in a Clinically relevant Mouse Model of [XLH].” I don’t actually understand many of the intensely scientific details here (and I keep misreading “Minicircle” as “miracle”), but the bottom line is that researchers are still working on a possible cure for XLH by way of gene therapy. This appears to be a different lab (in Asia) than the one I read about a few years ago in Europe. Since I’m focusing on the good instead of bad today, we’re going to ignore their misguided use of XLHR (hypophosphatemic rickets) instead of simply XLH. If they can cure XLH, I won’t care so much what they call it, because presumably they’ll be able to do it in childhood and eventually there won’t be any adults left with XLH!
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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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