A cross‐sectional multicenter study of osteogenesis imperfecta in North America – results from the linked clinical research centers

Abstract

Osteogenesis Imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n=544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean LS aBMD was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answer questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of “phenotypic expansion” driven by next-generation sequencing.

Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta: A Nationwide Register-Based Cohort Study

“…(8) A cross-sectional multicenter study of OI in North America that included 544 patients with a median age at inclusion at 12.6 years (range, 0 to 67 years) reported an average of 1.0 AE 3.0 fractures per individual in the year prior to enrolment. (7) Our data are more similar to a Norwegian population-based cohort study that included all known adult patients with OI, with a mean age of 44 AE 12 years (range, 25 to 83) at enrollment. (6) The authors reported an annual rate of 0.12 fractures per individual in the year prior to enrollment in the study.…”

“…Other studies reporting fracture rates in patients with OI have used questionnaires, structured interviews, or patient chart review, but did not include a reference population. (6)(7)(8) The unique personal identification number issued to all inhabitants of Denmark at birth or immigration enables individuallevel record linkage between different health registries. (9) The Danish National Patient Register (NPR) was established in 1977 and includes primary and supplementary diagnosis for all in-hospital contacts.…”

What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases

“…De novo mutations are frequent. [Patel et al, 2015] Many infants with OI type IV are fracture free at birth and have normal sclerae. Children with OI type IV may be small for their age and develop long bone bowing and fractures in childhood, but during the first two years of life, even in a family with OI, genetic testing might be required to confirm the diagnosis.…”

Causes of Osteoporosis in Pediatric Age Group Patients, Following at King Abdul Aziz University Hospital, Jeddah, Saudi Arabia: 12 Years Experience

“…By estimation the incidence rate of (OI) about 1-2 out of 20.000 births per year. Comparing to previous across-sectional multicenter study in North America, the prevalence of (OI) 1 in 15.000-20.000 birth [11]. Consanguinity was very prevalent among primary patients and that increases the risk of the offspring being affected with OI and juvenile osteoporosis.…”

“…reported in (57.3%) of the patients with primary osteoporosis ,while reported in (50%) in secondary, 36 patient (27.5%) of them were first degree relatives and 16 patients (12.2%) were second degree This finding consistent with previous studies using same method of our data collecting, it has proved that genetic is the most likely risk factor for idiopathic juvenile osteoporosis [1].Thirty one (23.7%) of children had positive family history of osteoporosis before the age of 50,and twenty one (16%) of children had positive family history of osteoporosis after the age of 50. In North America studies on (544) patient with OI the family history was present in (25%) [11].…”