Conventional Therapy in Adults With XLH Improves Dental Manifestations, But Not Enthesopathy.

Abstract

X-Linked hypophosphatemia (XLH; OMIM no. 307800) is an X-linked dominant disease due to inactivating mutations in the PHEX gene that increase fibroblast growth factor 23 (FGF23) expression in bone, resulting in renal phosphate wasting and inappropriately normal calcitriol concentrations (1). Although there are currently no approved therapies for XLH, high-dose calcitriol and phosphate salts have been the mainstay of therapy for the past three decades (1, 2). There is general agreement that most affected children should be treated (if the administration and safety of therapy can be adequately monitored), but there is a lack of consensus regarding when to treat adults (1, 2). Features of XLH that frequently affect adults include short stature, lower extremity deformity (from rickets during childhood), bone pain, pseudofractures, osteoarthritis, stiffness from enthesopathy, and tooth abscesses. Obviously, treating adult patients will not correct lower extremity deformities or short stature, and except for patients with pseudofractures, XLH patients do not have increased fracture risk (3). However, some investigators have reported improvements in bone pain and osteomalacia in treated adults (4). In this issue of the JCEM, Connor et al (5) report retrospective observations made in 52 XLH patients regarding two important disease manifestations, enthesopathy and dental disease. Unfortunately, there are no large prospective trials on the effects of medical therapy on enthesopathy or dental disease. As for many other rare diseases, large, prospective, randomized, controlled trials are not feasible. The present study is the largest to date on the effect of therapy on these two disease manifestations, and it provides important information for the care of persons having XLH.