April 2026 Research Update

This month, real-world studies paint a mixed but clearer picture of what people may and may not notice after starting burosumab. In a prospective follow-up program, many lab measures and several patient-reported symptoms improved and stayed improved for up to 3 years. In insurance-claims data focused on prescription pain medicines, pain-medication use changed little after burosumab, suggesting that day-to-day pain management may not shift quickly for everyone, at least as captured by prescriptions. [1] [2]

In the XLH Disease Monitoring Program (139 people, including ages often left out of trials), average blood phosphate improved by Year 1 and stayed improved at Year 3. Children also showed improvement in rickets-related measures and reported less pain interference, while changes in fatigue and mobility were not clearly significant in this dataset. Adults reported improvements in pain, stiffness, and physical function, with more adults reaching meaningful symptom improvements by Year 3 than by Year 1. [1]

In administrative claims (387 adults and 524 children), prescription pain medication use was common before burosumab and was mostly similar after starting it. Adults had little change in prescription pain medication or opioid claims after initiation. Children also showed little change in the first year, with a modest decrease in prescription pain medication use reported in the second year. [2]

Taken together, these studies add context for what improvement can look like in everyday settings: blood tests and some symptom reports may improve over time for many people on burosumab, but prescription-based measures of pain treatment may not shift much in the short term. This may matter now mainly for understanding expectations when reading about burosumab results, because different studies measure different parts of daily life (labs, symptom questionnaires, and prescriptions). What remains uncertain is how well prescription claims reflect lived pain, and how much longer follow-up is needed to see clearer changes in pain and pain-medication use. [1] [2]

This month reinforces that adult XLH often involves a long-term burden that goes beyond lab values, especially for bones, teeth, and daily functioning. Across two real-world cohorts, many adults reported reduced quality of life and many had substantial skeletal and dental problems documented in clinic records. The studies also show that adults are not all managed the same way, with a mix of conventional therapy, burosumab, and no active XLH-directed treatment reported in one national cohort. [3] [4]

In 170 Italian adults, skeletal deformities and dental disease were common, and males had heavier skeletal involvement than females. Cardiovascular conditions such as hypertension were also recorded, and the study noted that hypertension was linked with higher FGF23 (a hormone involved in phosphate control) in this dataset. Testing practices varied, with FGF23 measured in a minority of participants, while genetic testing found PHEX mutations in most of those tested. [4]

In a French registry of 123 adults, quality-of-life scores were lower than typical population norms for both physical and mental health. Physical scores were worse in people who were older, not working, or had a fracture or surgery history, which fits with the idea that cumulative complications can affect daily life. Mental health scores were worse in younger adults in this dataset, showing that emotional and social impacts may not track the same way as physical limitations. [3]

These studies mainly add understanding about what adult XLH can look like at a population level, including the mix of bone, dental, and daily-life effects that may accumulate over time. They may matter now by helping patients and caregivers put individual experiences (pain, stiffness, fractures, dental problems, and work limitations) into a broader context where these issues are commonly reported. What remains uncertain is how much any one factor, including current treatments, explains quality-of-life differences, because these studies describe patterns rather than proving cause and effect. [4] [3]

This month adds detail about how XLH can shape growth and body proportions in childhood, and it also sharpens what is known about teeth and hearing-related problems as part of the condition. A long-term pediatric follow-up suggests that conventional phosphate and active vitamin D supplements did not fully prevent growth differences through adolescence. Smaller cross-sectional studies add clearer descriptions of dental findings and of an inner-ear disorder pattern that appeared mainly in males with complete loss of PHEX function. [5] [6] [7]

In 198 children followed from birth to age 18 while receiving oral phosphate and active vitamin D, the study reported a higher risk of being small for gestational age and increasing body disproportion in the first 2 years. Final height was reduced despite supplementation, alongside signs of ongoing metabolic bone activity such as persistent low phosphate and rising alkaline phosphatase scores. Starting supplements early because of a known family history did not prevent the overall pattern of growth shortfall reported here. [5]

In a 17-person dental evaluation spanning ages 4 to 61 years, spontaneous dental abscesses and gum disease were frequently observed, along with distinctive tooth shape and root features seen on dental imaging. Among adults in this group, the average number of decayed, missing, or filled teeth was reported as 14, higher than the national Brazilian mean. This helps make the dental side of XLH more concrete by describing the kinds of changes dentists may see. [6]

In 33 adults who had detailed hearing and balance testing plus PHEX gene dosage assessment, bilateral Meniere disease with endolymphatic hydrops (MD-hp) was reported in 6 individuals, all hemizygous males. Females did not meet MD-hp criteria in this cohort, although some had hearing loss without vertigo. The authors interpreted the pattern as consistent with a PHEX gene-dosage threshold, where more remaining PHEX activity may relate to milder ear findings. [7]

These studies may matter now mostly by clarifying what problems can be part of XLH across the lifespan, even when treatment is used. The growth study describes long-term patterns under conventional supplementation, which can help families understand why growth and body proportion concerns may still come up in follow-up. The dental and hearing studies do not change diagnosis or monitoring on their own, but they make the range of possible tooth and ear-related issues more specific, and they highlight that some ear patterns in XLH may differ by sex and PHEX variant type. [5] [6] [7]

This month includes early research and biomarker studies that aim to connect PHEX changes to what is happening in bone at a biological level. In children on burosumab, blood markers of bone building and breakdown were still abnormal in a cross-sectional snapshot, even though some measures improved compared with prior treatment history. Separately, laboratory work on a specific PHEX deletion variant reported reduced PHEX protein expression, adding one more piece to how certain variants might disrupt mineral handling. [8] [9]

In 107 burosumab-treated children, multiple bone turnover markers were higher than reference values, and signaling markers involved in bone remodeling (the RANKL/OPG balance and sclerostin) were shifted. The study also reported that blood phosphate and alkaline phosphatase improved compared with prior treatment, but mild low phosphate persisted on average. Children who started burosumab as their primary therapy showed partial normalization of some osteoblast-related activity compared with those previously treated with phosphate and active vitamin D. [8]

A separate laboratory-focused paper examined a PHEX deletion variant called p.Thr605MetfsTer14 and reported that it reduced PHEX protein expression and promoted mineralization in the experimental system used. This supports the idea that certain PHEX changes can directly alter mineralization biology, although lab findings cannot predict how a person will do clinically. The variant protein also showed altered localization and reduced stability, which helps explain why less PHEX protein was present in the experimental system. It mainly adds detail about one possible disease mechanism for a specific variant. [9]

These studies are most relevant for understanding what researchers are still trying to measure and explain, rather than for immediate changes in care. The biomarker study suggests that even with burosumab, bone activity signals in blood may not fully normalize, which may help explain why symptoms and complications can be complex and variable. The lab variant study is early research that may matter later if linked to patient outcomes, but on its own it does not tell an individual what to expect. [8] [9]

A single case report this month describes an unusual combination of conditions in one person with XLH. The report documents XLH due to a PHEX missense variant together with polyostotic fibrous dysplasia, which the authors describe as the first reported co-occurrence. The person had improvement in blood phosphorus and bone pain after treatment with oral phosphate and calcitriol. [10]

This report may matter mainly as a reminder that rare overlaps can occur, and that genetic testing can clarify the specific PHEX change involved in an individual. Because it is one patient, it cannot tell how common this combination is or what it means for others with XLH. It adds to the medical record of XLH variability but is not a basis for broad conclusions. [10]