The following is a summary of “X-Linked Hypophosphatemia, Not Only a Skeletal Disease But Also a Chronic Inflammatory State,” published in the December 2022 issue of Endocrinology & Metabolism by Méaux, et al.

A primary overproduction of fibroblast growth factor 23 (FGF23) leads to a rare genetic condition known as X-linked hypophosphatemia (XLH). However, these mechanisms have not been looked at in XLH. FGF23 has been linked to inflammation and poor osteoclastogenesis. For a study, researchers sought to determine if XLH patients had an unusual inflammatory profile and elevated osteoclastic activity.

By using real-time quantitative polymerase chain reaction on peripheral blood mononuclear cells (PBMCs) purified from total blood samples taken from patients and healthy control individuals, they conducted a prospective, multicenter, cross-sectional study to examine the transcript expression of 8 inflammatory markers (Il6, Il8, Il1, CXCL1, CCL2, CXCR3, Il1R, Il6R). From the PBMCs of XLH patients, the impact of native/active vitamin D on osteoclast development was also evaluated in vitro.

There were 28 XLH patients (17 children, 6 of whom were receiving standard of care [SOC] & 11 receiving burosumab treatment) and 19 controls recruited. In PBMCs from XLH patients compared to controls, the expression of the majority of inflammatory markers was considerably higher. The burosumab & SOC groupings did not vary from one another. Significantly fewer osteoclasts were formed in XLH patients. When compared to cells from the burosumab subgroup, XLH mature osteoclasts had lower levels of inflammatory markers (as opposed to SOC).

For the first time, they reported an odd inflammatory profile in XLH. They proposed that inflammation may be a key factor in these extraskeletal consequences of XLH because XLH patients were more likely to develop arterial hypertension, obesity, and enthesopathies, and because inflammation might make the clinical outcomes worse.