X-Linked Hypophosphatemia, Not Only a Skeletal Disease But Also a Chronic Inflammatory State

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Endocrinology

Background:

• X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by elevated fibroblast growth factor 23 (FGF23).
• FGF23 is implicated in inflammation and impaired osteoclastogenesis, but these mechanisms are not well-understood in XLH.
• XLH is associated with extraskeletal complications like hypertension and obesity, potentially influenced by inflammation.

Purpose of the Study:

• To investigate the inflammatory profile in XLH patients.
• To assess osteoclast activity and formation in XLH.
• To explore the impact of burosumab therapy on these parameters.

Main Methods:

• Prospective, multicenter, cross-sectional study.
• Real-time quantitative PCR analysis of 8 inflammatory markers in peripheral blood mononuclear cells (PBMCs) from 28 XLH patients and 19 controls.
• In vitro assessment of osteoclast formation and inflammatory marker expression in XLH PBMCs, comparing standard of care (SOC) with burosumab treatment.

Main Results:

• XLH patients exhibited significantly increased expression of most inflammatory markers in PBMCs compared to controls.
• Osteoclast formation was significantly impaired in XLH patients.
• XLH osteoclasts showed higher inflammatory marker levels, which were reduced in the burosumab subgroup compared to SOC.

Conclusions:

• This study reveals a distinct inflammatory profile in XLH for the first time.
• Inflammation may play a crucial role in the extraskeletal manifestations of XLH, such as arterial hypertension, obesity, and enthesopathies.
• Burosumab therapy may modulate the inflammatory response in XLH osteoclasts.