There’s been a ton of research related to XLH (and the other chronic hypophosphatemias), but since phosphate-wasting affects so many parts of the human body, there’s still work to be done! It’s part of what makes now an amazing time to be doing science — we’ve started to understand the biochemistry of the human body, but there are still more questions than answers.
Some examples of questions I have:
Dental issues: Will burosumab treatment prevent (or at least reduce) our spontaneous abscesses? It seems likely that if treatment is begun whiles kids’ adult teeth are still developing (in the non-XLH population, the pulp chambers generally get smaller over time as the area around them fills in with mineralized material, but that doesn’t happen in untreated or even phos/calcitriol-treated XLHers), then their bodies’ access to adequate phosphorus should allow their teeth to fill in correctly. But what about adults who didn’t have access to burosumab during childhood but start it as adults? There’s some preliminary evidence that burosumab treatment does help reduce abscesses in kids, but the results are conflicting, with two journal articles that seem to reach opposite conclusions, and they both have really small sample sizes, so the authors acknowledge more research needs to be done. Compare the less than encouraging conclusion (continuing abscesses and no filling-in of the dentin around the pulp chambers) in “Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy” in Frontiers Endocrinology with the more encouraging conclusion (reduced number of dental abscesses in XLH children treated with burosumab compared to XLH children treated with phos/calcitriol, and interestingly, a greater reduction in dental abscesses in girls compared to boys) in “Burosumab and Dental Abscesses in Children With X-Linked Hypophosphatemia” in JBMR Plus.
You can tell from the conflicting results that we need to know more about the pediatric experience, and we also need to see if adults, like the kids in the study, maybe also experience fewer abscesses while on burosumab compared to the old phos/calcitriol treatment.
Autosomal hypophosphatemia treatment: Do patients with autosomal versions of chronic hypophosphatemia benefit from burosumab? There’s one tiny study (just two patients, who are brothers, so they have the same genetic variation) that suggests burosumab would be effective. But we need a broader study, across several genetic variants, to tell us more about who might benefit and who might not. Knowing which mutation can be treated with burosumab would also be important for gene therapy, and might tell us more about chronic hypophosphatemia in general, like the lingering question of why some patients have more severe symptoms than others, even within a family (meaning they have the same PHEX mutation, but might have some other genetic code that worsens or ameliorates the symptoms).
Hearing! There’s practically no research whatsoever about hearing loss and tinnitus in the chronic hypophosphatemia communities. There is one study on mice, which found poor mineralization of certain ear bones, which might cause hearing issues, but no studies that I can find about hearing issues in human hypophosphatemia patients.
Respiratory issues: I know of one XLHer who has had so much calcification around her ribs that she has serious difficulty inflating her lungs enough to breathe! There was one small study into lung capacity in a handful of XLHers, but the results were never published. I started to think about the issue after my heart surgery, when I used an inspirometer (tool to measure how much air is being inhaled, as a measure of how well the lungs are expanding, which can be an issue after anesthesia). I never got anywhere close to a “normal” reading, and I was never sure if I was being limited by the effects of the surgery or by some pre-existing calcification that prevented my lungs from expanding fully or by some other unknown cause.
Arm/hand issues: I’m thinking particularly about nerve impingements, like those of carpal or ulnar tunnel syndromes. Are XLHers more susceptible to them (my completely unscientific impression from my own experience and talking to others is that we are more susceptible, but patients and their doctors may not realize it’s connected to the XLH, so it’s not discussed much and definitely hasn’t been studied)? And if so, is there anything we can do to prevent them? Will burosumab treatment reduce their incidence or progression of the symptoms? And more generally, are there other symptoms affecting our arms that are overlooked, because most of the focus by researchers is on the legs and spine, so the arms are forgotten?
Ask patients: I’d love to see researchers listening to patients’ stories before hypothesizing a research project. Wouldn’t it be great to have a gathering where researchers could ask patients what questions we have, not so they could answer those questions, but purely as a brainstorming session, to trigger their own questions that need to be answered? Scientific research is a creative process, especially coming up with the initial hypothesis to be studied, and creativity requires breaking out of preconceived notions — like the long-held belief that XLH is a pediatric bone disorder — to see the subject in a different light. Even someone fully steeped in the existing science of XLH might not be aware of the issues we experience daily that have never been acknowledged in a medical journal and that we may not even be sure are related to our XLH. A nurturing environment where we could ask questions that might seem too stupid to mention in another setting (like when seeking care for an acute problem) might open up all sorts of avenues of research.
What about you? What issues would you like to see researched? I’m sure there are plenty of things I haven’t thought of. You can drop a note to gin at ginjones dot com, for the next time I compile a list of topics that need answers (or, if I know the answer, I’ll try to address it in a future post).
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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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