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

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2-related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2-related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.

Joint Replacements in Individuals With Skeletal Dysplasias: One Institution's Experience and Response to Operative Complications.

BACKGROUND: Skeletal dysplasias are a heterogeneous group of >400 genetic disorders characterized by abnormal bone growth. Many individuals experience joint pain and limitation, coming to require joint replacement much earlier than the average-statured population. In addition, prosthesis survival rate is less in the dysplastic population. The purpose of this study is to identify risk factors for surgery and provide recommendations to improve surgical outcomes. METHODS: This a retrospective review of 29 individuals with a skeletal dysplasia who had 64 joint replacements between April 1985 and January 2019 at a single institution. We collected demographics, physical examination, medical history, imaging studies, surgical indication, and complications. RESULTS: Spondyloepiphyseal dysplasia was the most common skeletal dysplasia (7), followed by pseudoachondroplasia (4) and multiple epiphyseal dysplasia (4). Average age of the cohort was 40.6 years (range 14-64). Hip arthroplasty (34) was the most commonly performed surgery. The majority of arthroplasties (75%) required custom components. Complication rate was 37.3%, most commonly pulmonary embolism (3) and pneumonia (3). Most complications (81.8%) occurred in individuals with either a pre-existing cardiopulmonary comorbidity or lumbar/sacral deformity. Body mass index did not correlate with complication severity (R = -0.042, P = .752) or rate (R = 0.006, P = .963). CONCLUSION: Surgical complications are highest in patients with pre-existing cardiopulmonary conditions. Body mass index does not predict complications in this cohort. Preoperative evaluations for individuals with skeletal dysplasias should include comprehensive work-up of spine issues and extraskeletal systems that present an operative risk. Intraoperative protocol should include special consideration for placement on the table, airway maintenance, and spinal cord monitoring in select cases.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant-age LS aBMD data points. Though all OI subtypes were examined, primary analyses were restricted to type I OI (OI-1). Using linear regression, we constructed expected OI-1 LS aBMD-for-age curves from the data from individuals who had never received BPN. LS aBMD in those who had been exposed to BPN was then compared with the computed expected aBMD. BPN exposure in preadolescent years (age <14 years) was associated with a LS aBMD that was 9% more than the expected computed values in BPN-naïve individuals (p < 0.01); however, such association was not observed across all ages. Exposure to i.v. BPN and treatment duration >2 years correlated with LS aBMD in preadolescent individuals. BPN exposure also had a significant association with non-aBMD clinical outcome variables. Logistic regression modeling predicted that with BPN exposure, a 1-year increase in age would be associated with an 8.2% decrease in fracture probability for preadolescent individuals with OI-1, compared with no decrease in individuals who had never received any BPN (p < 0.05). In preadolescent individuals with OI-1, a 0.1 g/cm2 increase in LS aBMD was associated with a 10.6% decrease in scoliosis probability, compared with a 46.8% increase in the BPN-naïve group (p < 0.01). For the same changes in age and LS aBMD in preadolescent individuals, BPN exposure was also associated with higher mobility scores (p < 0.01), demonstrating that BPN treatment may be associated with daily function. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Bone robusticity in two distinct skeletal dysplasias diverges from established patterns.

Achondroplasia (ACH) is a heritable disorder of endochondral bone formation characterized by disproportionate short stature. Osteogenesis imperfecta (OI) is a heritable bone and connective tissue disorder characterized by bone fragility. To investigate bone morphology of these groups, we retrospectively reviewed 169 de-identified bone age films from 20 individuals with ACH, 39 individuals with OI and 37 age- and sex-matched controls (matched to historical measurements from the Bolton-Brush Collection). We calculated robustness (Tt.Ar/Le) and relative cortical area (Ct.Ar/Tt.Ar) from measurements of the second metacarpal, which reflect overall bone health. Relative cortical area (RCA) is a significant predictor of fracture risk and correlates with robustness at other sites. Individuals with OI had RCH values above and robustness values below that of the control population. Bisphosphonate treatment did not significantly impact either robustness or RCA. In contrast to that reported in the unaffected population, there was no sexual dimorphism found in OI robustness or relative cortical area. We suggest that the underlying collagen abnormalities in OI override sex-specific effects. Individuals with ACH had robustness values above and RCA values below that of the control population. Sexual dimorphism was found in ACH robustness and RCH values. CLINICAL SIGNIFICANCE: Identifies morphologic trends in two distinct skeletal dysplasia populations (OI and ACH) to better understand development of bone robusticity and slenderness in humans. Understanding these patterns of bone morphology is important to predict how individuals will respond to treatment and to increase treatment effect. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2392-2396, 2017.