Prevalence of enthesopathies in X-linked hypophosphatemia: an explorative ultrasound study

X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by renal phosphate wasting, leading to rickets in children and osteomalacia in adults. An underrecognized symptom in adults with XLH is enthesopathy, leading to pain and reduced quality of life. Although enthesopathies primarily affect tendon insertions, they are closely linked to the underlying bone pathology of XLH, reflecting mineralization defects characteristic of osteomalacia. This study aimed to determine the prevalence of enthesopathies in XLH patients using ultrasound and assess their association with pain and physical function. This cross-sectional study included 26 XLH patients (mean age: 37.9 ± 17.1 yr, 76.9% female). Ultrasound examinations assessed 6 tendons of the upper and 10 tendons of the lower extremity in adolescents and adults with XLH. Laboratory tests included phosphate, alkaline phosphatase, and i-FGF23 levels. Physical performance was evaluated using the 6-min walk test (6MWT) and the chair rising test. Pain was assessed using the brief pain inventory. Enthesopathies were detected by ultrasound in 84.6% of patients, affecting predominantly the lower extremities (80.8%) but also the upper extremities (50%). The quadriceps and achilles tendons were the most frequently affected sites. Enthesopathy prevalence increased with age (r = 0.61, p < .05) and negatively correlated with 6MWT performance (r = -0.4, p = .04). No significant association was found between enthesopathies and BMI or pain scores. Based on the worst pain scale, 73.1% of patients reported mild pain. Inter-rater agreement for ultrasound assessment was good to very good/excellent. Enthesopathies of the lower, but also upper extremities are common features of XLH. Their presence correlates with reduced mobility, emphasizing the need for targeted interventions. The exact pathophysiological mechanisms remain unclear, but age appears to be a key factor.