Finally, I’ve got the promised information on what I think primary care providers (PCPs) and emergency-care providers need to know for overseeing the care of XLH adults.
You’ve probably all experienced the challenge of convincing a health care provider that some of the counter-intuitive aspects of XLH are true, e.g., that giving phosphorus to a patient with a phosphate-wasting disorder will actually lower our blood phosphorus levels. Or even that XLH is a whole-body, whole-life disorder, not a temporary, pediatric condition. But it’s not really feasible to bring a stack of journal articles to every appointment, and PCPs seldom have either the time or inclination to read such advanced, detailed, and lengthy articles. I’ve occasionally brought the “Whole Body, Whole Life, Whole Family: Patients’ Perspectives on X-Linked Hypophosphatemia” article with me to appointments with a new clinician, since I’m one of the listed authors, and could use that to establish my credentials when I absolutely, positively needed the doctor to listen to me. That’s not really an option for most patients though, and it feels a bit silly.
Which is why I think we need something that’s shorter and more focused on the basics than the too-complicated, niche journal articles, and yet still contains the evidence for the information, by way of footnotes, for those who don’t believe things that “only a patient” says. That’s what I’ve tried to create here, for PCPs (and ER staff) working with XLH adults. I hope to have a similar document for PCPs overseeing XLH kids’ care next month. In the meantime, please keep in mind that the following is still a draft, and I’d love to hear from you about anything I may have missed or gotten wrong. I’ll incorporate feedback and make the final versions available by the end of the year. I’m also still looking for a footnote for the statement that bisphosphonates are contraindicated for XLH patients (or anyone with a mineral metabolism disorder). It used to be in the label for Fosamax, but I checked, and it’s not now.
As always, I’m not a doctor, just a well-read patient. The issues I focused on here are the ones I’ve seen my own PCPs struggle with, or that I’ve struggled to explain repeatedly to disbelieving health care providers. I would really have liked to have something like this when I was in the emergency room, having just been diagnosed with a heart attack, and the ICU doctor wanted to talk about XLH instead, starting with the suggestion that he should prescribe bisphosphonates to better treat my XLH.
So, what do you think? Am I missing an important basic health-care topic (for adults)? Is there anything I can cut to make it simpler and quicker to read? Keep in mind that I’m trying to stick to absolute basics, so it could be printed (double-sided) on a single sheet of paper, to increase the odds that the clinician would actually read it.
What PCP and ER staff need to know about adult XLH patients
What is XLH? X-linked Hypophosphatemia is a dominant genetic phosphate-wasting disorder with musculoskeletal symptoms. [Fn 1-5; see Fn 9 for dominant transmission pattern] The ICD10 code is 83.31 (familial hypophosphatemia), but you may also see outdated terms in the patient’s history, which you should NOT use, i.e., hypophosphatemic rickets, Vitamin D Resistant Rickets.
What is the standard of care? Generally, if adults are on treatment, it will be either burosumab (anti-FGF23 monoclonal antibody, injection every 28 days) or phosphate supplements with calcitriol (less effective, more side effects, needs to be closely monitored by clinician with XLH experience). [Fn 1-5] At a minimum, adults should be treated pharmacologically to stabilize bone metabolism several months in advance of any orthopedic surgery, or if they have persistent pain and/or unhealed fractures (including pseudofractures). [Fn 1-5] Many experts and informed patients believe that life-long treatment, even in the absence of severe symptoms, is advisable, because XLH is a progressive disorder with symptoms that cannot be reversed once they begin. [Fn 3-5, 7]
Who are the appropriate specialists for referral? XLH is a whole-body disorder that affects virtually every system. [Fn 1-5, 7] The metabolic issues (excessive FGF23, phosphate wasting, hyperparathyroidism) are generally treated by an endocrinologist (or sometimes a nephrologist) with a specific interest in bone metabolism. Once the metabolic issues are addressed, there may still be a variety of other symptoms that need specialized treatment. Virtually all patients develop serious dental issues, especially spontaneous abscesses that will require endodontic treatment. [Fn 8] Virtually all patients experience chronic pain, either in the bones or in the joints, and may benefit from referral to pain management. [Fn 1-5] Note that XLH patients are likely to have an extremely high pain tolerance, so reports of pain levels may be significantly understated. [Fn 7] Referrals to other specialties may also be appropriate, depending on the patient’s needs, i.e., orthopedic surgery, rheumatology, audiology, neurology, occupational therapy, physical therapy, and/or talk therapy. [Fn 1-6]
What laboratory tests or imaging should be done? The XLH specialist will likely order annual blood tests related to phosphorus, calcium, vitamin D, and (very important!) PTH, sometimes with urine testing as well. [See Fn 10 for normal phosphorus values. Be sure to use age-appropriate values.] The XLH specialist will also likely order a kidney scan every few years to check for calcification, especially if the patient is on the old phosphorus/calcitriol regimen. [Fn 1-5] The XLH specialist will also order a DXA scan if appropriate, but note that DXA scans can be misleading if not reviewed by an expert in rare bone metabolism. [Fn 4,5]
Should I prescribe Vitamin D, calcium, or phosphorus supplements? Absolutely not! These supplements can act counterintuitively in XLH patients, with phosphorus supplements actually decreasing the blood phosphorus levels or harming the kidneys and parathyroids. [Fn 5] Phosphorus supplements are especially contraindicated for patients while on burosumab. [Fn 5, 11] Bisphosphonates are also generally contraindicated for XLH patients, whether or not on any other treatment.
What comorbidities should I watch for? A lot remains unknown about the progression of XLH in adults, especially later in life, and symptom severity varies wildly even within a single family [Fn 1, 2], but the almost universal symptoms affecting the patient’s quality of life as an adult are chronic bone pain, dental abscesses, early-onset arthritis, and widespread enthesopathy (calcification of soft tissue, especially tendons and ligaments, sometimes progressing to spinal stenosis). [Fn 1-5, 7] There is also a known correlation between XLH and obesity (partly due to mobility issues and partly metabolic) [Fn 3, 4], and a suspected one between XLH and hypertension (pain, plus mobility restrictions, plus salt in phosphorus supplements) [Fn 4, 5]. While excessive FGF23 levels correlate with heart disease in the general population, suggesting that XLH patients could have an elevated risk of heart disease, there is no known correlation between XLH and any form of heart disease. [Fn 4] There is a correlation between XLH and CKD, mainly due to old treatment (phosphate supplements may cause nephrocalcinosis and/or kidney stones) and/or hyperparathyroidism. [Fn 4, 5]
Where can I get more information? The pharmaceutical company, Kyowa Kirin, has a website for clinicians here: https://www.kyowakirinhub.com/en-sa/therapy-areas/phosphate-dysregulation/x-linked-hypophosphatemia/disease-pages/adult-xlh
The International XLH Alliance has several resources here: https://xlhalliance.org/resources/
Footnotes:
1: “XLH Matters 2022” https://link.springer.com/article/10.1186/s13023-023-02883-3
2: “XLH Matters: an evolving programme” https://link.springer.com/article/10.1186/s13023-024-03387-4
3: “XLH Matters 2024”
https://link.springer.com/article/10.1186/s13023-025-03930-x
4: “XLH Management in Adults: Clinical Practice Guideline” https://pubmed.ncbi.nlm.nih.gov/40243526/
5: “Clinical practice recommendations for the diagnosis and management of X-linked hypophosphatemia.” https://pubmed.ncbi.nlm.nih.gov/39814982/
6 : “An Evidence-based Physical Therapy Prescription for Adults With X-linked Hypophosphatemia” https://pubmed.ncbi.nlm.nih.gov/35795809/
7: “Voice of the Patient,” report from the Symposium on Hypophosphatemia, a 2018 Externally-Led Patient Focused Drug Development Meeting
https://xlhnetwork.org/wp-content/uploads/2023/05/VOP-XLH-Final.pdf
8: “Diagnosis and management of X-linked hypophosphatemia in dental practice: A scoping review” https://pubmed.ncbi.nlm.nih.gov/42409089/
Footnote 9: National Cancer Institute (X-linked dominant transmission) https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/x-linked-dominant-inheritance
Footnote 10: Normal phosphorus
From the UNC Medical Center: https://www.uncmedicalcenter.org/mclendon-clinical-laboratories/available-tests/phosphorus/
From Mayo Clinic Laboratories https://www.mayocliniclabs.com/api/sitecore/TestCatalog/DownloadTestCatalog?testId=8408
Footnote 11: FDA-approved label for Crysvita (burosumab): https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761068s009lbl.pdf
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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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