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Item Burosumab Therapy in Children with X-Linked Hypophosphatemia(Massachusetts Medical Society, 2018-05) Carpenter, Thomas O.; Whyte, Michael P.; Imel, Erik A.; Boot, Annemieke M.; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A.; Medicine, School of MedicineBACKGROUND X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. METHODS In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. RESULTS The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. CONCLUSIONS In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets.Item Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension(BMJ, 2021) Briot, Karine; Portale, Anthony A.; Brandi, Maria Luisa; Carpenter, Thomas O.; Cheong, Hae Ii; Cohen-Solal, Martine; Crowley, Rachel K.; Eastell, Richard; Imanishi, Yasuo; Ing, Steven; Insogna, Karl; Ito, Nobuaki; de Beur, Suzanne Jan; Javaid, Muhammad K.; Kamenicky, Peter; Keen, Richard; Kubota, Takuo; Lachmann, Robin H.; Perwad, Farzana; Pitukcheewanont, Pisit; Ralston, Stuart H.; Takeuchi, Yasuhiro; Tanaka, Hiroyuki; Weber, Thomas J.; Yoo, Han-Wook; Nixon, Annabel; Nixon, Mark; Sun, Wei; Williams, Angela; Imel, Erik A.; Medicine, School of MedicineObjectives: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. Methods: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT). Results: Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks. Conclusions: Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function.Item Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial(Elsevier, 2019-06-15) Imel, Erik A.; Glorieux, Francis H.; Whyte, Michael P.; Munns, Craig F.; Ward, Leanne M.; Nilsson, Ola; Simmons, Jill H.; Padidela, Raja; Namba, Noriyuki; Cheong, Hae Il; Pitukcheewanont, Pisit; Sochett, Etienne; Högler, Wolfgang; Muroya, Koji; Tanaka, Hiroyuki; Gottesman, Gary S.; Biggin, Andrew; Perwad, Farzana; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Martin, Javier San; Portale, Anthony A.; Medicine, School of MedicineBackground X-linked hypophosphatemia in children is characterized by elevated serum FGF23, hypophosphatemia, rickets, lower extremity bowing, and growth impairment. We compared the efficacy and safety of continuing conventional therapy, consisting of oral phosphate and active vitamin D, versus switching to burosumab, a fully human monoclonal antibody against FGF23, in pediatric X-linked hypophosphatemia. Methods In this randomised, active-controlled, open-label, phase 3 trial at 16 clinical sites, we enrolled children with X-linked hypophosphataemia aged 1–12 years. Key eligibility criteria were a total Thacher rickets severity score of at least 2·0, fasting serum phosphorus lower than 0·97 mmol/L (3·0 mg/dL), confirmed PHEX (phosphate-regulating endopeptidase homolog, X-linked) mutation or variant of unknown significance in the patient or a family member with appropriate X-linked dominant inheritance, and receipt of conventional therapy for at least 6 consecutive months for children younger than 3 years or at least 12 consecutive months for children older than 3 years. Eligible patients were randomly assigned (1:1) to receive either subcutaneous burosumab starting at 0·8 mg/kg every 2 weeks (burosumab group) or conventional therapy prescribed by investigators (conventional therapy group). Both interventions lasted 64 weeks. The primary endpoint was change in rickets severity at week 40, assessed by the Radiographic Global Impression of Change global score. All patients who received at least one dose of treatment were included in the primary and safety analyses. The trial is registered with ClinicalTrials.gov, number NCT02915705. Findings Recruitment took place between Aug 3, 2016, and May 8, 2017. Of 122 patients assessed, 61 were enrolled. Of these, 32 (18 girls, 14 boys) were randomly assigned to continue receiving conventional therapy and 29 (16 girls, 13 boys) to receive burosumab. For the primary endpoint at week 40, patients in the burosumab group had significantly greater improvement in Radiographic Global Impression of Change global score than did patients in the conventional therapy group (least squares mean +1·9 [SE 0·1] with burosumab vs +0·8 [0·1] with conventional therapy; difference 1·1, 95% CI 0·8–1·5; p<0·0001). Treatment-emergent adverse events considered possibly, probably, or definitely related to treatment by the investigator occurred more frequently with burosumab (17 [59%] of 29 patients in the burosumab group vs seven [22%] of 32 patients in the conventional therapy group). Three serious adverse events occurred in each group, all considered unrelated to treatment and resolved. Interpretation Significantly greater clinical improvements were shown in rickets severity, growth, and biochemistries among children with X-linked hypophosphataemia treated with burosumab compared with those continuing conventional therapy. Funding Ultragenyx Pharmaceutical Inc. and Kyowa Kirin InternationalItem Burosumab vs conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period(Oxford University Press, 2024-01-04) Ward, Leanne M.; Högler, Wolfgang; Glorieux, Francis H.; Portale, Anthony A.; Whyte, Michael P.; Munns, Craig F.; Nilsson, Ola; Simmons, Jill H.; Padidela, Raja; Namba, Noriyuki; Cheong, Hae, Il; Sochett, Etienne; Muroya, Koji; Tanaka, Hiroyuki; Pitukcheewanont, Pisit; Gottesman, Gary S.; Biggin, Andrew; Perwad, Farzana; Chen, Angel; Merritt, John Lawrence, II; Imel, Erik A.; Medicine, School of MedicineIn a randomized, open-label phase 3 study of 61 children aged 1-12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64-88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.Item Burosumab vs Phosphate/Active Vitamin D in Pediatric X-Linked Hypophosphatemia: A Subgroup Analysis by Dose Level(The Endocrine Society, 2023) Imel, Erik A.; Glorieux, Francis H.; Whyte, Michael P.; Portale, Anthony A.; Munns, Craig F.; Nilsson, Ola; Simmons, Jill H.; Padidela, Raja; Namba, Noriyuki; Cheong, Hae Il; Pitukcheewanont, Pisit; Sochett, Etienne; Högler, Wolfgang; Muroya, Koji; Tanaka, Hiroyuki; Gottesman, Gary S.; Biggin, Andrew; Perwad, Farzana; Chen, Angel; Scott Roberts, Mary; Ward, Leanne M.; Medicine, School of MedicineContext: In an open-label, randomized, controlled, phase 3 trial in 61 children aged 1 to 12 years with X-linked hypophosphatemia (XLH), burosumab improved rickets vs continuing conventional therapy with active vitamin D and phosphate. Objective: We conducted an analysis to determine whether skeletal responses differed when switching to burosumab vs continuing higher or lower doses of conventional therapy. Methods: Conventional therapy dose groups were defined as higher-dose phosphate [greater than 40 mg/kg] (HPi), lower-dose phosphate [40 mg/kg or less] (LPi), higher-dose alfacalcidol [greater than 60 ng/kg] or calcitriol [greater than 30 ng/kg] (HD), and lower-dose alfacalcidol [60 ng/kg or less] or calcitriol [30 ng/kg or less] (LD). Results: At week 64, the Radiographic Global Impression of Change (RGI-C) for rickets was higher (better) in children randomly assigned to burosumab vs conventional therapy for all prebaseline dose groups: HPi (+1.72 vs +0.67), LPi (+2.14 vs +1.08), HD (+1.90 vs +0.94), LD (+2.11 vs +1.06). At week 64, the RGI-C for rickets was also higher in children randomly assigned to burosumab (+2.06) vs conventional therapy for all on-study dose groups: HPi (+1.03), LPi (+1.05), HD (+1.45), LD (+0.72). Serum alkaline phosphatase (ALP) also decreased in the burosumab-treated patients more than in the conventional therapy group, regardless of on-study phosphate and active vitamin D doses. Conclusion: Prior phosphate or active vitamin D doses did not influence treatment response after switching to burosumab among children with XLH and active radiographic rickets. Switching from conventional therapy to burosumab improved rickets and serum ALP more than continuing either higher or lower doses of phosphate or active vitamin D.Item Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period(Springer, 2019-09-01) Portale, Anthony A.; Carpenter, Thomas O.; Brandi, Maria Luisa; Briot, Karine; Cheong, Hae II; Cohen-Solal, Martine; Crowley, Rachel; Jan De Beur, Suzanne; Eastell, Richard; Imanishi, Yasuo; Imel, Erik A.; Ing, Steven; Ito, Nobuaki; Javaid, Muhammad; Kamenicky, Peter; Keen, Richard; Kubota, Takuo; Lachmann, Robin; Perwad, Farzana; Pitukcheewanont, Pisit; Ralston, Stuart H.; Takeuchi, Yasuhiro; Tanaka, Hiroyuki; Weber, Thomas J.; Yoo, Han-Wook; Zhang, Lin; Theodore-Oklota, Christina; Mealiffe, Matt; San Martin, Javier; Insogna, Karl; Medicine, School of MedicineBurosumab, a fully human monoclonal antibody to FGF23, is the only approved treatment for X-linked hypophosphatemia (XLH), a rare genetic disorder characterized by renal phosphate wasting and substantial cumulative musculoskeletal morbidity. During an initial 24-week randomized, controlled trial, 134 adults with XLH received burosumab 1 mg/kg (n = 68) or placebo (n = 66) every 4 weeks. After 24 weeks, all subjects received open-label burosumab until week 48. This report describes the efficacy and safety of burosumab during the open-label treatment period. From weeks 24–48, serum phosphorus concentrations remained normal in 83.8% of participants who received burosumab throughout and were normalized in 89.4% who received burosumab after placebo. By week 48, 63.1% of baseline fractures/pseudofractures healed fully with burosumab, compared with 35.2% with burosumab after placebo. In both groups, burosumab was associated with clinically significant and sustained improvement from baseline to week 48 in scores for patient-reported outcomes of stiffness, pain, physical function, and total distance walked in 6 min. Rates of adverse events were similar for burosumab and placebo. There were no fatal adverse events or treatment-related serious adverse events. Nephrocalcinosis scores did not change from baseline by more than one grade at either week 24 or 48. These data demonstrate that in participants with XLH, continued treatment with burosumab is well tolerated and leads to sustained correction of serum phosphorus levels, continued healing of fractures and pseudofractures, and sustained improvement in key musculoskeletal impairments.Item Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia(Endocrine Society, 2022) Ward, Leanne M.; Glorieux, Francis H.; Whyte, Michael P.; Munns, Craig F.; Portale, Anthony A.; Högler, Wolfgang; Simmons, Jill H.; Gottesman, Gary S.; Padidela, Raja; Namba, Noriyuki; Cheong, Hae Il; Nilsson, Ola; Mao, Meng; Chen, Angel; Skrinar, Alison; Scott Roberts, Mary; Imel, Erik A.; Medicine, School of MedicineContext: Younger age at treatment onset with conventional therapy (phosphate salts and active vitamin D; Pi/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The effect of age on burosumab efficacy and safety in XLH is unknown. Objective: This work aimed to explore the efficacy and safety of burosumab vs Pi/D in younger (< 5 years) and older (5-12 years) children with XLH. Methods: This post hoc analysis of a 64-week, open-label, randomized controlled study took place at 16 academic centers. Sixty-one children aged 1 to 12 years with XLH (younger, n = 26; older, n = 35) participated. Children received burosumab starting at 0.8 mg/kg every 2 weeks (younger, n = 14; older, n = 15) or continued Pi/D individually titrated per recommended guidelines (younger, n = 12; older, n = 20). The main outcome measure included the least squares means difference (LSMD) in Radiographic Global Impression of Change (RGI-C) rickets total score from baseline to week 64. Results: The LSMD in outcomes through 64 weeks on burosumab vs conventional therapy by age group were as follows: RGI-C rickets total score (younger, +0.90; older, +1.07), total Rickets Severity Score (younger, -0.86; older, -1.44), RGI-C lower limb deformity score (younger, +1.02; older, +0.91), recumbent length or standing height Z-score (younger, +0.20; older, +0.09), and serum alkaline phosphatase (ALP) (younger, -31.15% of upper normal limit [ULN]; older, -52.11% of ULN). On burosumab, dental abscesses were not reported in younger children but were in 53% of older children. Conclusion: Burosumab appears to improve outcomes both in younger and older children with XLH, including rickets, lower limb deformities, growth, and ALP, compared with Pi/D.Item Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia(Elsevier, 2016-12) Ruppe, Mary D.; Zhang, Xiaoping; Imel, Erik A.; Weber, Thomas J.; Klausner, Mark A.; Ito, Takahiro; Vergeire, Maria; Humphrey, Jeffrey S.; Glorieux, Francis H.; Portale, Anthony A.; Insogna, Karl; Peacock, Munro; Carpenter, Thomas O.; Department of Medicine, IU School of MedicineX-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). Objective Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody. Methods Twenty-eight adult outpatients with XLH received up to four doses of KRN23 administered subcutaneously every 28 days. General HRQoL was measured with the SF-36v2 and condition-related HRQoL with the WOMAC at baseline and study endpoint as a secondary outcome of a Phase 1/2, open-label, multicenter, dose-escalation trial. Results Testing for scale discriminant validity and convergent-divergent validity supported the use of these scales in the assessment of HRQoL in XLH. Both instruments indicated impairment of physical function at baseline with all mean scores showing a trend to improved health at study endpoint compared to baseline. When corrected for multiple comparisons, the score for Role Limitations due to physical health on the SF-36v2 which measures the patient's perception of their own chronic functional impairments due to poor physical health remained significantly improved (P < 0.05), increasing to the mean score of US adults. For the WOMAC, Physical Functioning and Stiffness scores were significantly improved (P < 0.05). Conclusion KRN23 administration was associated with significantly improved patient perception of their Physical Functioning and Stiffness due to their disease. This study demonstrates that the SF-36v2 and WOMAC are valid tools for assessing HRQoL in XLH.Item Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia(Oxford University Press, 2022) Weber, Thomas J.; Imel, Erik A.; Carpenter, Thomas O.; Peacock, Munro; Portale, Anthony A.; Hetzer, Joel; Merritt, J. Lawrence, II; Insogna, Karl; Medicine, School of MedicineContext: Burosumab was developed as a treatment option for patients with the rare, lifelong, chronically debilitating, genetic bone disease X-linked hypophosphatemia (XLH). Objective: Collect additional information on the safety, immunogenicity, and clinical response to long-term administration of burosumab. Methods: UX023-CL203 (NCT02312687) was a Phase 2b, open-label, single-arm, long-term extension study of adult subjects with XLH who participated in KRN23-INT-001 or KRN23-INT-002 studies. The long-term UX023-CL203 study (January 5, 2015 through November 30, 2018) provided data up to 184 weeks. Participants in UX023-CL203 received burosumab based on the last dose in the prior KRN23-INT-001 or KRN23-INT-002 studies (0.3, 0.6, or 1.0 mg/kg given by subcutaneous injection every 4 weeks). At Week 12, burosumab could be titrated upward/downward to achieve fasting serum phosphate levels within the normal range. Primary objectives included long-term safety, the proportion of subjects achieving fasting serum phosphate in the normal range, changes in bone turnover markers, patient-reported outcomes for pain and stiffness, and measures of mobility. Results: Fasting serum phosphate levels at the midpoint of the dosing interval (2 weeks postdose, the time of peak effect) were within the normal range in 85% to 100% of subjects. Measures of phosphate metabolism and bone biomarkers generally improved with burosumab therapy, approaching or reaching their respective normal ranges by study end. Improvements in patient-reported outcomes and mobility were sustained throughout the observation period. No new safety findings emerged with longer-term burosumab treatment. Conclusion: These data support the conclusion that burosumab therapy may be a safe and effective long-term treatment option for adult patients with XLH.Item Nephrocalcinosis and kidney function in children and adults with X-linked hypophosphatemia: baseline results from a large longitudinal study(Oxford University Press, 2024) Portale, Anthony A.; Ward, Leanne; Dahir, Kathryn; Florenzano, Pablo; Ing, Steven W.; Jan de Beur, Suzanne M.; Martin, Regina M.; Meza-Martinez, Adriana I.; Paloian, Neil; Ashraf, Ambika; Dixon, Bradley P.; Khan, Aliya; Langman, Craig; Chen, Angel; Wang, Christine; Scott Roberts, Mary; Tandon, P. K.; Bedrosian, Camille; Imel, Erik A.; Medicine, School of MedicineBackground: In patients with X-linked hypophosphatemia (XLH), conventional therapy with oral phosphate salts and active vitamin D has been associated with nephrocalcinosis. However, the nature of the relationships among XLH, its treatment, nephrocalcinosis, and kidney function remain poorly understood. Methods: Renal ultrasounds were performed and glomerular filtration rates were estimated (eGFR) at baseline in burosumab-naïve patients with XLH who participated in burosumab clinical trials (NCT02181764, NCT02526160, NCT02537431, NCT02163577, NCT02750618, NCT02915705) or enrolled in the XLH Disease Monitoring Program (XLH-DMP; NCT03651505). In this cross-sectional analysis, patient, disease, and treatment characteristics were described among patients with and without nephrocalcinosis. Results: The analysis included 196 children (mean [SD] age 7.6 [4.0] yr) and 318 adults (40.3 [13.1] yr). Mean (SD) height z-score was -1.9 (1.2) for children and -2.3 (1.7) for adults. Nearly all children (97%) and adults (94%) had previously received conventional therapy. Nephrocalcinosis was detected in 22% of children and 38% of adults. In children, reduced eGFR <90 mL/min/1.73 m2 was more prevalent in those with nephrocalcinosis (25%) than in those without (11%), a finding that was not observed in adults. Children with nephrocalcinosis had lower mean values of TmP/GFR (p<.05), serum 1,25(OH)2D (p<.05), and eGFR (p<.001) and higher mean serum calcium concentrations (p<.05) than did those without nephrocalcinosis. Adults with nephrocalcinosis had lower mean serum phosphorus (p<.01) and 1,25(OH)2D (p<.05) concentrations than those without. Exploratory logistic regression analyses revealed no significant associations between the presence of nephrocalcinosis and other described patient or disease characteristics. Conclusions: Nephrocalcinosis was observed in nearly one-quarter of children and more than one-third of adults with XLH. Further study is needed to better understand the predictors and long-term consequences of nephrocalcinosis, with surveillance for nephrocalcinosis remaining important in the management of XLH.