Researchers are finally taking seriously the symptom that many, but not all, XLHers experience, and that has a major adverse effect on daily life: hearing loss. There are now two published journal articles discussing research (in mice, not humans) on the bones in the ears, which (if I’m reading it right, and remember, I’m not a doctor) might lead to better understanding of the hearing loss in XLH.
It’s long been speculated that XLHers’ hearing loss and tinnitus are due to something going wrong with our ear bones, but no one knew exactly what it was. I always thought it could be from the build-up of calcifications (like what happens in our joints), but this new research changes the conversation somewhat, with the suggestion that the ear bones have too little phosphorus, and that’s what causes the hearing loss. In that case, I’m not sure why we don’t all have hearing loss, or we don’t all have it early in life (as opposed to developing it with age), but I suppose it could be that we start out a little unmineralized, not enough to affect hearing, but over time, more phosphorus is lost, and that’s when we notice the hearing deteriorating. I’m just speculating, but now we have a little research on the issue.
The first article is “Conductive hearing loss in the Hyp mouse model of X-linked hypophosphatemia is accompanied by hypomineralization of the auditory ossicles” in JBMR (September 2021). Note that “Hyp” mice have a genetic mutation comparable to the one for XLH in humans, so the research is specific to hypophosphatemia.
If I’m understanding the science right, the researchers found that ear bones of Hyp mice were, unsurprisingly, less well mineralized than those in regular mice. They concluded, “our findings highlight the importance of ossicular mineralization for hearing conduction and point towards the potential benefit of improving mineralization to prevent hearing loss in XLH.”
My takeaway is that if XLHers can get their ear bones properly mineralized in childhood (and/or don’t lose phophorus from their ear bones in adulthood), they won’t experience the hearing loss that’s associated with XLH. This seems to me to be one more reason why burosumab has the potential for far better outcomes than the old phos/calcitriol treatment. There aren’t any studies comparing ear-bone mineralization on burosumab v. old treatment, but anecdotally, based on the number of XLHers who had the old treatment in childhood and still developed hearing loss, it seems highly unlikely that the old treatment was particularly effective in mineralizing the ear bones. We know that burosumab is better at mineralizing bones in general, so I’m hopeful that burosumab will do better for the ear bones too, but it will take some time to know for sure, while we wait to see whether patients who are on burosumab early in life go on to develop hearing loss.
Less directly applicable to XLH, but still potentially contributing to our understanding of ear-bone mineralization is “Hypermineralization of Hearing-Related Bones by a Specific Osteoblast Subtype” in JBMR (April 2021). Note that the discussion is NOT specific to XLH, and the researchers were NOT use hyp mice. This article is about comparing how ear bones are mineralized to how other bones in the body are mineralized, and noting the differences.
The science of this article is mostly too advanced for me, but I think the gist of it is pretty simple — the bones in the ears need to be well mineralized (what they somewhat confusingly call “hypermineralized” which apparently means more like “adequately mineralized” rather than “overly mineralized”) for good hearing. And then they conclude: “We show that both organic and inorganic components of hypermineralized ear bones exhibit properties distinct from those of conventional bones.”
I think what they’re saying is that it now appears that the ear bones are somehow different from, say, leg bones or arm bones. My takeaway for the XLH community is that if they can figure out more details of that difference, it might shed light on our hearing loss, including how it could be treated, and and why some of us have hearing loss and some don’t.
And now I can’t stop humming the song, “Dem Bones” — “Toe bone’s connected to the foot bone … head bone’s connected to the neck bone.” — Except I’m changing the end to: “the head bone’s connected to the ear bones!”
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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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