August 2026 Research Update

This month added a clearer picture that common bone density scans can give mixed signals in XLH, especially when comparing the spine with the arms and legs. In a small comparison study, people with XLH receiving calcitriol and oral phosphate had higher spine bone density scores but lower bone density at a forearm site compared with similar people without XLH. More detailed bone imaging also showed thinner or less well-connected internal bone structure at peripheral sites, suggesting that "normal" results in one area may not reflect bone quality everywhere. [1]

The study measured bone density at the lumbar spine and at the 33% distal radius (a forearm site), and also used a high-detail scan of peripheral bones. The spine readings looked higher in the XLH group, while the forearm readings looked lower, and several participants met a threshold the authors used for low bone density for age. On the detailed scans, the XLH group had lower overall bone mineral density and worse trabecular measurements (the inner "lattice" of bone), especially at the distal tibia (near the ankle). [1]

One practical point from these results is that the measurement site mattered, and the authors highlighted the 33% radius as a potentially useful extra location when high-detail scans are not available. They also noted that spine DXA results can be hard to interpret in XLH, which may partly explain why the spine and peripheral sites did not match. Because this was a one-time snapshot in 16 treated patients, it does not show how bone measures change over time. [1]

For patients, this mainly helps explain why bone density results can be confusing in XLH, with some sites looking "better" and others looking "worse" at the same time. It does not test a new treatment or show whether one type of scan predicts fractures or pain, but it supports the idea that checking more than one bone site may give a fuller picture of bone health in XLH. What remains uncertain is how well these scan differences relate to day-to-day outcomes and long-term risk, because the study was small and looked at one moment in time. This matters now as context for understanding test results, and later if future studies connect these scan findings to symptoms and outcomes. [1]

This month, studies involving burosumab (an antibody that targets FGF23) added early clues in two very different areas: pregnancy exposure and possible immune effects. A single reported pregnancy continued burosumab without clear drug-related short-term problems for mother or infant, but newborn blood tests showed extremely high measured FGF23 that fell quickly over months. Separately, small lab studies using patient-derived immune cells suggested that burosumab treatment was linked to a shift away from a more inflammatory immune-cell state, which could point to effects beyond phosphate levels. [2] [3]

In the pregnancy case report, the baby had a very high intact FGF23 level on day 2 after birth, followed by a rapid decline over the first months, and imaging showed no rickets during infancy. The authors raised the possibility that burosumab-FGF23 immune complexes could make FGF23 measurements look higher than they truly are, which matters because families may see lab values that are hard to interpret. By 1 year, no developmental delays or adverse skeletal events were described in this child, but longer follow-up was not available. [2]

In the lab-focused study, macrophages (a type of immune cell) from untreated children with XLH showed more markers of an M1 state, which is often described as more inflammatory, and higher TRPV1, a protein linked to pain signaling in some settings. Macrophages from burosumab-treated children showed the opposite pattern, with more M2 markers and reduced TRPV1, and burosumab also lowered measured FGF23 levels in these cells. Because this was ex vivo and in vitro work in small groups, it cannot show that these changes happen in the whole body or translate directly into symptom changes, but it offers a testable explanation for future research. [3]

For patients and caregivers, these findings mainly add context rather than changing anything now. The pregnancy report provides a real-world example of continued burosumab during pregnancy with reassuring early infant development, while also warning that newborn FGF23 lab results may be misleading because of how the drug interacts with the test. The immune-cell study is early research that may matter later if confirmed, because it suggests burosumab could affect inflammation-related pathways, but it does not show benefits or risks in daily life outcomes. What remains uncertain is safety across many pregnancies and whether immune-cell changes connect to pain, fatigue, or bone outcomes in larger human studies. [2] [3]

This month reinforced that dental problems in XLH are not only about cavities, but often involve the tooth's internal structure. A report describing two patients with newly identified PHEX variants found consistent dentin and pulp changes on imaging and close-up tooth analysis. A literature-based comparison in the same paper described similar patterns across many previously reported patients, pointing to dentin-pulp abnormalities as a central part of XLH dental findings. [4]

In the two patients, dental radiographs showed enlarged pulp chambers and irregular pulp shape, and ultrastructural analysis showed defects in dentin (the hard tissue under enamel), including irregular areas and disrupted tubules. The authors also summarized prior reports describing clinical dental problems such as pulp necrosis (death of the tooth nerve), tooth loss, and periodontitis. These findings fit together as a picture where the tooth may be more vulnerable from the inside out, even without obvious decay. [4]

For patients, this is most useful as an explanation for why tooth infections, unexpected tooth pain, or early tooth loss can happen in XLH even without obvious decay. The evidence here is based on a very small number of closely studied patients plus a review of past reports, so it does not tell how often a given problem will happen to any one person. It does, however, make the underlying reason clearer: changes in dentin and the pulp area appear to be common across reported XLH dental descriptions. This matters now mainly for understanding symptoms and planning research, and later if studies link specific dental findings to prevention or long-term outcomes. [4]