ESPE Abstracts (2021) 94 P1-51

ESPE2021 ePoster Category 1 Bone B (10 abstracts)

A Global Natural History Study (NHS) of Fibrodysplasia Ossificans Progressiva (FOP): Normal Long Bone Growth and Abnormalities in Younger Patients over 36 Months

Robert J. Pignolo 1 , Geneviève Baujat 2 , Matthew A. Brown 3 , Carmen De Cunto 4 , Edward C. Hsiao 5 , Richard Keen 6 , Mona Al Mukaddam 7 , Rose Marino 8 , Aude Houchard 9 & Frederick S. Kaplan 7

1Department of Medicine, Mayo Clinic, Rochester, MN, USA; 2Département de Génétique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France; 3Guy’s and Thomas’ NHS Foundation Trust and King’s College London NIHR Biomedical Research Centre, London, United Kingdom; 4Pediatric Rheumatology Section, Department of Pediatrics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 5Division of Endocrinology and Metabolism, the UCSF Metabolic Bone Clinic, the Institute of Human Genetics, and the UCSF Program in Craniofacial Biology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; 6Centre for Metabolic Bone Disease, Royal National Orthopaedic Hospital, Stanmore, United Kingdom; 7Departments of Orthopaedic Surgery and Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 8Ipsen, Newton, MA, USA; 9Ipsen, Boulogne-Billancourt, France

Background: FOP is an ultra-rare, severely disabling genetic disorder characterised by progressive heterotopic ossification. The median age at diagnosis is 5 years and patients are supported by multiple specialties. We describe normal long bone growth changes and incidence of bone abnormalities in participants with FOP aged <18 years in a 3-year, prospective, global NHS (NCT02322255).

Methods: Individuals with FOP aged ≤65 years with a documented ACVR1R206H mutation were enrolled. Normal long bone growth changes and abnormalities were assessed over 36 months. Linear growth assessments and knee height measurements were completed in triplicate; linear height was measured with a stadiometer and knee height with a knee caliper. Femur/tibia lengths and abnormalities of epiphyseal plates were determined using low-dose whole-body computed tomography (WBCT).

Results: 114 individuals were included in the Full Analysis Set at Baseline; 66 were aged <18 years. Mean (standard deviation [SD]) change from Baseline to Month 36 in femur and tibia length was highest in males aged <10 at Baseline (6.42 [1.78] cm, n = 5) and females aged <8 at Baseline (5.46 [0.69] cm, n = 2), respectively, and lowest in males aged 14-<18 at Baseline (0.18 [0.63] cm/0.28 [0.45] cm, n = 5). Mean (SD) change in knee height from Baseline to Month 36 was highest in females aged <8 at Baseline (6.75 [0.64] cm, n = 2), and lowest in males aged 14-<18 at Baseline (1.48 [1.32] cm, n = 5). Some participants recorded knee height losses. No female participants aged 14-<18 at Baseline had measurements for femur/tibia length or knee height at Month 36. Linear height z-scores decreased over 36 months. Mean (SD) z-scores at Baseline were 0.70 (1.04), 0.08 (1.32) and 0.09 (1.41) for participants aged <8, 8-<15 and 15-<18 years, respectively; the smallest decrease occurred in participants aged <8 at Baseline (-0.09 [0.73], n = 8), and the greatest decrease occurred in participants aged 15-<18 at Baseline (-0.96, n = 1). At Baseline, 26 (39.4%) participants aged <18 years had a bone abnormality at knee epiphyseal plates; at Month 36, 9/22 (40.9%) had a recorded abnormality. All knee abnormalities were dense metaphyseal lines. No hand/wrist abnormalities were reported.

Conclusions: Knee height losses and decreasing linear height z-scores, particularly in adolescent participants, highlight difficulties associated with obtaining accurate growth and height measurements in patients with FOP who have worsening skeletal deformities over time. Incidence of knee abnormalities appeared to remain stable over 36 months, although WBCT is less sensitive than radiographs in detecting such bone abnormalities.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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