A multicenter study to evaluate pulmonary function in osteogenesis imperfecta

Abstract

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV which do not follow the expected trends of the normal population. We also show that "normalization" of FVC and FEV using general population data to generate percent predicted values underestimates the pulmonary involvement in OI. Within each subtype of OI, we used linear mixed models to find potential correlations between FEV and FVC with the clinical variables including mobility, bisphosphonate use, and scoliosis. Our results are an important step in understanding the extent of pulmonary involvement in individuals with OI and for developing pulmonary endpoints for use in the routine patient care as well as in the investigation of new therapies.

Pediatric Outcomes Data Collection Instrument is a Useful Patient-Reported Outcome Measure for Physical Function in Children with Osteogenesis Imperfecta

“…Rare bone diseases account for 5 percent of all birth defects and encompass over 400 conditions 14,15 . Osteogenesis imperfecta (OI), a prototypic rare bone disorder, is characterized by bone fragility, hearing loss, dental abnormalities, scoliosis, cardiopulmonary problems, joint laxity, and muscle weakness 16,17 . Disease severity ranges from individuals with a few fractures, to those with severe skeletal deformities, to perinatal lethality 16 .…”

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study

“…The establishment of the OI LCRC and the participants enrolled in the longitudinal study have been previously described (Bellur et al, ; Jain et al, ; Patel et al, ; Tam et al, ). The OI LCRC enrolled total of 552 patients between 2009 and 2013 at the following sites: Baylor College of Medicine (Houston, TX); Kennedy Krieger Institute (Baltimore, MD); Nemours/Alfred I. DuPont Hospital for Children (Wilmington, DE); Oregon Health & Science University and Shriners Hospital for Children (Portland, OR); Shriners Hospital for Children (Chicago, IL); and Shriners Hospital for Children (Montreal, QC).…”

“…The establishment of the OI LCRC and the participants enrolled in the longitudinal study have been previously described (Bellur et al, 2016;Jain et al, 2019;Patel et al, 2015;Tam et al, 2018 Overall, 312 individuals with OI who had audiometric data available were included in this analysis (Table 1); 93 were enrolled by the LCRC and 219 were enrolled by the BBDC. For individuals that were enrolled in both studies (n = 11), only data from the latest and most comprehensive audiogram were included.…”

Osteogenesis Imperfecta: New Perspectives From Clinical and Translational Research

“…Lung histology is also abnormal in several mouse models of OI . In addition, lung function can be affected by scoliosis …”

“…(51)(52)(53) In addition, lung function can be affected by scoliosis. (52,54,55) Sleep apnea, a disorder characterized by pauses in breathing, affects 1% to 6% of adults and 2% of children in the general population. (56) Sleep apnea can lead to serious health issues, such as cardiovascular disease; through increased daytime sleepiness, it increases the risk of accidents.…”