Growth Curves for Children with X-linked Hypophosphatemia

Meng Mao, Thomas O Carpenter, Michael P Whyte, Alison Skrinar, Chao-Yin Chen, Javier San Martin, Alan D Rogol, Meng Mao, Thomas O Carpenter, Michael P Whyte, Alison Skrinar, Chao-Yin Chen, Javier San Martin, Alan D Rogol

Abstract

Context: We characterized linear growth in infants and children with X-linked hypophosphatemia (XLH).

Objective: Provide linear growth curves for children with XLH from birth to early adolescence.

Design: Data from 4 prior studies of XLH were pooled to construct growth curves. UX023-CL002 was an observational, retrospective chart review. Pretreatment data were collected from 3 interventional trials: two phase 2 trials (UX023-CL201, UX023-CL205) and a phase 3 trial (UX023-CL301).

Setting: Medical centers with expertise in treating XLH.

Patients: Children with XLH, 1-14 years of age.

Intervention: None.

Main outcome measure: Height-for-age linear growth curves, including values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for children with XLH compared to population norms.

Results: A total of 228 patients (132 girls, 96 boys) with 2381 height measurements were included. Nearly all subjects (> 99%) reported prior management with supplementation therapy. Compared to the Center for Disease Control and Prevention growth curves, boys at age 3 months, 6 months, 9 months, 1 year, and 2 years had median height percentiles of 46%, 37%, 26%, 18%, and 5%, respectively; for girls the median height percentiles were 52%, 37%, 25%, 18%, and 7%, respectively. Annual growth in children with XLH fell below that of healthy children near 1 year of age and progressively declined during early childhood, with all median height percentiles < 8% between 2 and 12 years old.

Conclusion: Children with XLH show decreased height gain by 1 year of age and remain below population norms thereafter. These data will help evaluate therapeutic interventions on linear growth for pediatric XLH.

Trial registration: ClinicalTrials.gov NCT02163577 NCT02750618 NCT02915705.

Keywords: FGF23; PHEX; X-linked hypophosphatemia; growth curve; rickets.

© Endocrine Society 2020.

Figures

Figure 1.
Figure 1.
Pooled datasets for XLH growth curves. Abbreviation: XLH, X-linked hypophosphatemia.
Figure 2.
Figure 2.
X-linked hypophosphatemia (XLH) and Center for Disease Control and Prevention (CDC) growth curves for boys. A: Boys ≤ 13 years of age. B: Boys ≤ 5 years of age. CDC growth curve lines (year 2000) for boys in blue, with the 50th percentile bolded. XLH growth curve lines in black: 5th, 10th, 25th, 50th (bolded), 75th, 90th, and 95th percentile generated from prior studies in the burosumab program before treatment with burosumab (Studies UX023-CL002, UX023-CL201, UX023-CL205, UX023-CL301). Grey dots (●) indicate individual XLH data points before treatment with burosumab. To smoothly transition from recumbent length to standing height, 0.8 cm was subtracted from recumbent length values before pooling data with standing height per established methodology from Kuczmarski et al (12).
Figure 3.
Figure 3.
X-linked hypophosphatemia (XLH) and Center for Disease Control and Prevention (CDC) growth curves for girls. A: Girls ≤ 13 years of age. B: Girls ≤ 5 years of age. CDC growth curve lines (year 2000) for girls in pink, with the 50th percentile bolded. XLH growth curve lines in black: 5th, 10th, 25th, 50th (bolded), 75th, 90th, and 95th percentile generated from prior studies in the burosumab program before treatment with burosumab (Studies UX023-CL002, UX023-CL201, UX023-CL205, UX023-CL301). Grey dots (●) indicate individual XLH data points before treatment with burosumab. To smoothly transition from recumbent length to standing height, 0.8 cm was subtracted from recumbent length values before pooling data with standing height per established methodology from Kuczmarski et al (12).

References

    1. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381–1388.
    1. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect. 2014;3(1):R13–R30.
    1. Cagnoli M, Richter R, Böhm P, Knye K, Empting S, Mohnike K. Spontaneous growth and effect of early therapy with calcitriol and phosphate in X-linked hypophosphatemic rickets. Pediatr Endocrinol Rev. 2017;15(Suppl 1):119–122.
    1. Mäkitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 2003;88(8):3591–3597.
    1. Glorieux FH, Marie PJ, Pettifor JM, Delvin EE. Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. N Engl J Med. 1980;303(18):1023–1031.
    1. Baroncelli GI, Bertelloni S, Ceccarelli C, Saggese G. Effect of growth hormone treatment on final height, phosphate metabolism, and bone mineral density in children with X-linked hypophosphatemic rickets. J Pediatr. 2001;138(2):236–243.
    1. Haffner D, Nissel R, Wühl E, Mehls O. Effects of growth hormone treatment on body proportions and final height among small children with X-linked hypophosphatemic rickets. Pediatrics. 2004;113(6):e593–e596.
    1. Lamb YN. Burosumab: first global approval. Drugs. 2018;78(6):707–714.
    1. Whyte MP, Carpenter TO, Gottesman GS, et al. Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(3):189–199.
    1. Imel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019;393(10189):2416–2427.
    1. Carpenter TO, Whyte MP, Imel EA, et al. Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med. 2018;378(21):1987–1998.
    1. Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC growth charts for the United States: methods and development. National Center for Health Statistics. Vital Health Stat 2002;11(246):1–190.
    1. Mao M, Carpenter TO, Whyte MP, et al. Supplemental material for “Growth Curves for Children with X-linked Hypophosphatemia,” Dryad, Dataset, 10.5061/dryad.sqv9s4n1w. 2020.
    1. Rogol AD, Hayden GF. Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr. 2014;164(5 Suppl):S1–14.e6.
    1. Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr. 1985;107(3):317–329.
    1. Kelly A, Winer KK, Kalkwarf H, et al. Age-based reference ranges for annual height velocity in US children. J Clin Endocrinol Metab. 2014;99(6):2104–2112.

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