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Context:Treatment of X-linked hypophosphatemia (XLH) with active vitamin D metabolites and phosphate can partially correct skeletal deformities. It is unclear whether therapy influences the occurrence of two major long-term morbidities in XLH: enthesopathy and dental disease.Objective:The objective of the study was to investigate the relationship between treatment and enthesopathy and dental disease in adult XLH patients.Design:The study was designed as observational and cross-sectional.Setting:The study was conducted at an academic medical center's hospital research unit.Participants:Fifty-two XLH patients aged 18 years or older at the time of the study participated in the study.Interventions:There were no interventions.Main Outcome Measures:The number of enthesopathy sites identified by radiographic skeletal survey and dental disease severity (more than five or five or fewer dental abscesses), identified historically, were measured.Methods:Associations between proportion of adult life and total life with treatment and number of enthesopathy sites were assessed using multiple linear regression, whereas associations between these exposure variables and dental disease severity were assessed using multiple logistic regression. All models were adjusted for confounding factors.Results:Neither proportion of adult nor total life with treatment was a significant predictor of extent of enthesopathy. In contrast, both of these treatment variables were significant predictors of dental disease severity (multivariate-adjusted global P= .0080 and P= .0010, respectively). Participants treated 0% of adulthood were more likely to have severe dental disease than those treated 100% of adulthood (adjusted odds ratio 25 [95% confidence interval 1.2–520]). As the proportion of adult life with treatment increased, the odds of having severe dental disease decreased (multivariate-adjusted Pfor trend = .015).Conclusions:Treatment in adulthood may not promote or prevent enthesopathy; however, it may be associated with a lower risk of experiencing severe dental disease.

Context:In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia.Objective:The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH.Design:Two sequential open-label phase 1/2 studies were done.Setting:Six academic medical centers were used.Participants:Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05–0.6 mg/kg); 22 entered a 12-month extension study (0.1–1 mg/kg).Intervention:KRN23 was injected sc every 28 days.Main Outcome Measure:The main outcome measure was the proportion of subjects attaining normal serum Pi and safety.Results:At baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3–7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9–85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile.Conclusions:Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.