Ready for a pop quiz? This should be easy for anyone living with, caring for, or treating XLH.
Which of the following statements are true and which are false?
- XLH is a form of rickets.
- XLH adults have “normal health.”
- The only troublesome symptoms for XLH adults are bow-leggedness and lack of height.
- Burosumab (Crysvita) cures XLH.
- XLH males are more seriously affected than XLH females.
- Phosphate supplementation (with activated vitamin D) is an effective treatment for children with XLH.
I’m pretty sure you quickly figured out that all of those statements are false. And yet, they persist in the minds of healthcare providers (and payers), to the detriment of patients.
- Journal articles continue to routinely describe XLH as a “form of rickets” or “the most common form of inherited rickets.” Laypeople may think of rickets as a collection of symptoms (soft bones, bowed legs), but to a clinician (especially one who has never treated an XLHer for the entire course of the patient’s life), “rickets” is a purely pediatric bone symptom (softening of the bones), which ends when the growth plates close. Accordingly, if XLH is a form of rickets, then adults cannot have XLH and certainly cannot have any symptoms serious enough to require treatment. Which leads to some of the other misconceptions, especially about adults with XLH, but also to non-bone/tooth treatment for kids (i.e., muscle function and fatigue).
- Medscape, you should be really ashamed of yourself. In the article on “hypophosphatemic rickets” (one demerit right there for the title, and another demerit for the apparent failure to have the article reviewed by any experts who have ever treated even a single adult XLHer before lecturing on the adult experience), you state: “Apart from the short stature of most affected adults, the prognosis for a normal lifespan and normal health is good.” Seriously? SERIOUSLY? I can understand why clinicians before, say, the year 2000 were prone to say that once the growth plates closed, XLHers would go on to have normal health, other than being short and bow-legged. They were wrong, but might be excused since it wasn’t widely documented. But today? When there is ample patient testimony to the contrary, which is supported by multiple journal articles? How is it possible that this statement is still included in an otherwise reputable website? Could this kind of misinformation have anything to do with why a shocked twenty-something XLHer contacted me recently, having been told ten years ago (in the early 2010s) that they were done with their XLH symptoms and would have no further issues, only to find out now that their pain, fatigue, dental abscesses, hearing loss, and micro/pseudofractures are all due to XLH, and the patient is on the path to significant disability from enthesopathy?
- This so-called fact of XLH being nothing more than a heigh issue persists despite ample evidence to the contrary. The issue goes far beyond the Medscape article listed above, although I don’t have a good citation for how widespread this obsession with height is, just an impression from a lot of sources. It sometimes feels like everyone other than the patients themselves (at least among adults) thinks the most important question about burosumab is whether it will allow pediatric patients to reach their full height, and if not, the question implies, then maybe burosuamb treatment isn’t worthwhile. See, for example, this recent journal article, “Growth hormone treatment improves final height in children with X-linked hypophosphatemia.” I believe the focus on height, consciously or subconsciously, reflects a subconscious belief that that’s all that matters to patients. And, sure, we’d all love to be taller, and it’s especially an issue during childhood (and among parents of spontaneous cases who haven’t yet seen that height is far from the biggest challenge we experience). But in adulthood? With very few exceptions among the XLHers I’ve talked to, height just isn’t much of an issue. Fixing that would be a luxury, not a necessity. We’re much more concerned with the pain, fatigue, hearing loss, lack of mobility and potential for disability. See, e.g., the survey results in the Voice of the Patient report, where adults responded to a question about which symptom had the biggest negative impact on their life, and 30% chose “Mobility or range of motion issues” and only 6% chose height. Another survey, which collected information on kids as well as adults, showed that height was a much bigger issue for kids than for adults (which makes sense, because kids haven’t developed as many of the later-onset symptoms and disability as adults have). When asked about the biggest negative impact, only about two percent of adults chose height, while about eleven percent of kids chose height. In that survey, the top answer for adults was chronic pain, while for kids, the top answer was lower limb deformities, followed in second place by chronic pain. Bottom line: any clinician who thinks lower limb deformity and short stature are the defining characteristics of XLH over the course of the patient’s life pretty clearly has little, if any, exposure to adults with XLH.
- I really wish burosumab was a cure. It’s highly effective in normalizing blood phosphate levels. But only as long as the patient remains on the treatment. A cure implies one-and-done, not a lifetime of monthly/semi-monthly injections. And a cure addresses ALL of the symptoms, not just the most visible ones. There’s a theory, I think, in the minds of some clinicians and payers, that if they can just get pediatric XLHers’ bones fully mineralized and straight during childhood, then, in essence, the patients will be cured and won’t need treatment as adults. It’s the unstated (and false) assumption, I believe, behind the decisions to deny XLH adults treatment in countries with socialized medicine. After all, if XLH is solely about bone mineralization, and adults’ only issues are limb deformities and height, then sure, burosumab can be seen as a cure for any child who has access to that treatment. Then, the theory goes, as long as kids can get burosumab until their bones are straight and strong, they won’t need it after their bones stop growing. (Ignore, for the moment, all the current adults who didn’t have burosumab as kids, and all the kids who started it partway through their childhood.) There’s an emotional appeal to that theory, that it could be possible to pay for an extremely expensive treatment for a limited number of years, and get a good outcome. But, again, the problem is that it assumes that the only symptoms that matter are straight, (temporarily) mineralized (and therefore tall) bones, when we know that there’s so much more to hypophosphatemia than height and bone deformity. Bones require replenishment of minerals, so just because a patient’s bones are nicely stuffed with phosphorus at age twenty doesn’t mean that they’ll be similarly mineralized at age thirty. (Seriously? Who would think that? Have they never heard of osteoporosis, the other poor mineralization issue, involving calcium instead of phosphorus? Would anyone seriously think that someone who had good amounts of calcium in their bones at age 20 could then go the rest of their lives with a condition that wasted the calcium they ingested?) And poorly mineralized bones hurt and lead to enthesopathy. That pain and enthesopathy are major components in the top concerns of adult patients: mobility challenges and chronic pain.
- It’s long been theorized that XLH males have more serious symptoms than XLH females. Like with some of the other myths, it does make a bit of sense as a theory, based on the genetics. XLH women have two X chromosomes, and only one of them has the harmful variant (while men have only the one variant X chromosome and no second chromosome without the harmful variant), so maybe there is some protective benefit to women from the non-variant X). There is absolutely no evidence to support this conclusion however, and ample anecdotal evidence that it’s false. Just look at any picture that includes a significant number of adults with XLH, and you’ll see a wide range of visible disabilities, with no clear correlation to gender. Personally, and this is just my own, probably biased speculation, I wonder if the theory is actually based on sexism and the earlier false belief that height is the be-all/end-all of treatment goals, and height tends to be viewed as more important for men than for women.
- And finally, this widespread fiction is the one that really breaks my heart — the belief that the old phosphate/calcitriol treatment (often referred to as “standard” or “traditional” or “conventional” treatment) is anywhere near adequate. This too is based on the other fictions, starting with viewing XLH as a “form of rickets,” with adults having no symptoms other than shortness and bowed legs. Because, yes, in many cases, phosphate/calcitriol treatment (in best-case scenarios involving access to an expert clinician and consistent access to the pills) can (with some surgical assistance) straighten a pediatric patient’s legs, heal the rickets, and partially improve the bones’ mineralization. In at least one journal article I read recently, the clinician concluded this was good enough for some patients, so there was no point in prescribing state-of-the-art treatment. The only way that conclusion makes any sense whatsoever (it doesn’t really) is to discount the adult experience. Well before burosumab became available, XLHers observed, either in their own families or by interacting with other patients, that there was a sort of honeymoon period when they were okay without treatment. It lasted from the end of phos/calcitriol treatment around age 18, and continued through to the late twenties when their pain and fatigue (and sometimes fractures and enthesopathy) reached a point that they couldn’t ignore any longer, and they sought treatment again. We know, with absolute certainty, that any patient treated with phos/calcitriol today, who stops taking it by age 20, will be suffering by age 30. And the only way to prevent that eventual suffering is to go back in time and put them on burosumab instead of the phos/calcitriol and never stop treatment. But time travel isn’t possible. If the kids who were treated to phos/calcitriol in the past have access to burosumab as adults now, that may prevent or slow the worsening of the symptoms, but it will be too late to fix them.
I know this is long, and I appreciate your sticking with me to the end. I hope you can see now why I think the words we use to talk about XLH (and the other chronic hypophosphatemias) is so important. I have personally seen all of these myths still circulating to the detriment of patients. I was told by one clinician in the last year that it didn’t really matter what doctors call the disorder (rickets or hypophosphatemia), not when there was so much work to be done to improve access to treatment. Except the two are inextricably linked, as I’ve tried to lay out above — if a clinician, either consciously or subconsciously, thinks XLH = short and bow-legged, then it makes perfect sense to prescribe a cheap treatment that will solve both of those problems permanently (straighten/lengthen bones), rather than a more expensive treatment. Only a clinician who’s aware of the whole-body, whole-life nature of the disorder, will see that patients need state of the art treatment throughout their lives. Clinicians who can reject the old myths will then prescribe the state of the art treatment, and payers (insurers and government programs) who are educated about the false nature of those myths, will see the benefits of paying for it.
Words matter. Scientists who love their jargon should understand that! I will never, ever, ever understand the resistance to using more accurate terminology once the evidence is as overwhelming as what we have today to prove that XLH (and the other chronic hypophosphatemias) are not, in fact, a form of rickets.
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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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