Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy

Abstract

An inactivating PHEX gene mutation with the resultant accumulation of several mineralization-inhibiting proteins (e.g., FGF23) causes skeletal and dental morbidity in X-linked hypophosphatemia (XLH). This prospective case-control study explored the effect of burosumab, an anti-FGF23 antibody, on dental health of children with XLH. Ten children (age 4.3-15 years) with XLH underwent burosumab treatment per protocol. Assessment of their dental status at treatment initiation and after 1 and 3 years of treatment included clinical, laboratory and radiographic evaluation of rickets and dentition. Orthopantomographic examinations of ten healthy sex- and age-matched controls were selected for comparison. Coronal and pulp dimensions of a selected permanent mandibular molar were measured with Planmeca Romexis® software. One year of treatment led to improvement of height z-score (p=0.019) and healing of the rickets (p<0.001) in the XLH patients, and those achievements were maintained after three years of treatment. Dental morphology of XLH patients, distinguished by increased pulp-coronal ratios compared to controls (p=0.002), remained larger after the first year of treatment (p<0.001) and did not attain the decrease expected with age after three years of treatment. Five patients had a history of recurrent dental abscesses, with three having undergone at least one episode during the year before burosumab initiation. One patient sustained recurrent abscesses throughout three years of treatment. The persistence of the unique dental morphology of XLH patients undergoing burosumab therapy, as evidenced by excessively larger pulp dimensions, supports the role of other PHEX gene-related local mineralization inhibitors, such as osteopontin, in the pathogenesis of dental morbidity.

Characteristics of oral health of patients with X-linked hypophosphatemia: case reports and literature review

“…While information on the positive effects of burosumab on children's growth and biochemical profile has been accumulating since its introduction, there is a lack of data on its effects on dental health [58]. The effects on the potential prevention of periapical abscesses are particularly unclear [59].…”

X-Linked Hypophosphatemia: Does Targeted Therapy Modify Dental Impairment?

“…Clinical, radiographic, and laboratory evaluations of dental status were performed during the initiation of Burosumab therapy and after one and three years. Enlarged pulp chambers persisted after treatment with Burosumab, as demonstrated by larger pulp-tocoronal height and width ratios in XLH patients than in healthy controls [57]. Dental abscesses were significantly decreased during treatment with Burosumab.…”

“…A study by Kato et al supports the hypothesis that early treatment before the age of 5 years with phosphate supplements and vitamin D may have a preventive effect on dental complications [56]. Brener et al (2022) explored the effect of Burosumab on the dental health, dentition, and tooth morphology of ten children with XLH in a prospective case-control study [57]. They included children 8.8 ± 3.8 years old that who were diagnosed at a mean age of 1.9 ± 1.3 years and had been treated with conventional therapy for 7.0 ± 4.2 years [57].…”

“…Brener et al (2022) explored the effect of Burosumab on the dental health, dentition, and tooth morphology of ten children with XLH in a prospective case-control study [57]. They included children 8.8 ± 3.8 years old that who were diagnosed at a mean age of 1.9 ± 1.3 years and had been treated with conventional therapy for 7.0 ± 4.2 years [57]. Clinical, radiographic, and laboratory evaluations of dental status were performed during the initiation of Burosumab therapy and after one and three years.…”

Dental health of patients with X-linked hypophosphatemia: A controlled study

“…Data have shown that burosumab is more effective than conventional therapy in improving rickets, growth, lower limb deformity, and mobility in children with XLH ( 33 ). There is evidence that suggests that treatment with burosumab in children with XLH reduces the number of dental abscesses ( 25 , 34 ). However, further research is needed on the effects of burosumab on dental health in adult patients with XLH.…”