Is Osteogenesis Imperfecta Associated with Cardiovascular Abnormalities? A Systematic Review of the Literature.

Osteogenesis imperfecta (OI) is a rare genetic disorder caused by abnormal collagen type I production. While OI is primarily characterized by bone fragility and deformities, patients also have extraskeletal manifestations, including an increased risk of cardiovascular disease. This review provides a comprehensive overview of the literature on cardiovascular diseases in OI patients in order to raise awareness of this understudied clinical aspect of OI and support clinical guidelines. In accordance with the PRISMA guidelines, a systematic literature search in PubMed, Embase, Web of Science and Scopus was conducted that included articles from the inception of these databases to April 2023. Valvular disease, heart failure, atrial fibrillation, and hypertension appear to be more prevalent in OI than in control individuals. Moreover, a larger aortic root was observed in OI compared to controls. Various cardiovascular diseases appear to be more prevalent in OI than in controls. These cardiovascular abnormalities are observed in all types of OI and at all ages, including young children. As there are insufficient longitudinal studies, it is unknown whether these abnormalities are progressive in nature in OI patients. Based on these findings, we would recommend referring individuals with OI to a cardiologist with a low-threshold.

From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient's phenotype.

Bronchial obstruction in osteogenesis imperfecta can be detected by forced oscillation technique.

Introduction: Respiratory insufficiency is a leading cause of death in individuals with osteogenesis imperfecta (OI). However, evaluating pulmonary function in OI presents challenges. Commonly used pulmonary function tests such as spirometry and body plethysmography are sometimes difficult to perform for OI patients, and reference intervals are not always applicable. The forced oscillation technique (FOT) is a patient-friendly method for detecting respiratory abnormalities that requires no effort from the patient. Objective: This study investigates the feasibility of FOT in the evaluation of respiratory function in the clinical management of OI patients. Methods: Twelve OI patients, comprising eight with Sillence OI I, two with OI IV, and two with OI III, underwent spirometry, body plethysmography, and FOT, both pre-and post-administration of salbutamol. Results: FOT measurements exhibited consistent trends that aligned with spirometry and body plethysmography findings. The resistance at 8 Hz decreased after the administration of salbutamol, indicating that FOT is able to detect bronchial obstruction and its alleviation by medication (p < 0.05). The resonant frequency during expiration was higher than during inspiration in nearly all patients, suggesting obstructive disease. The technique gives insight into both inspiratory and expiratory impairment of pulmonary ventilation. The main FOT parameters showed a relatively high repeatability in duplicate measurements. Conclusion: Bronchial obstruction can be detected by FOT in patients with OI during quiet breathing, making it an easily executable alternative to other lung function measurements. The technique can detect the bronchodilator effect of sympathomimetic medication. It has the potential to provide information on expiratory flow limitation, pulmonary restriction, and reduced lung compliance.

Estradiol reference intervals in women during the menstrual cycle, postmenopausal women and men using an LC-MS/MS method.

BACKGROUND: For optimal medical decision-making, harmonized reference intervals for estradiol for different ages and both sexes are needed. Our aim was to establish reference intervals using a highly accurate and traceable LC-MS/MS method and to compare these with reference intervals in literature. METHODS: Estradiol was measured in serum obtained daily during the menstrual cycle of 30 healthy premenopausal women and in serum of 64 men and 33 postmenopausal women. The accuracy of our LC-MS/MS method was demonstrated by a method comparison with the CDC reference method. RESULTS: Our LC-MS/MS method was traceable to the reference method. Estradiol reference interval during the early follicular phase (days -15 to -6) was 31-771 pmol/L; during the late follicular phase (days -5 to -1) 104-1742 pmol/L; during the LH peak (day 0) 275-2864 pmol/L; during the early luteal phase (days +1 to +4) 95-1188 pmol/L; during mid luteal phase (days +5 to +9) 151-1941 pmol/L; during late luteal phase (days +10 to +14) 39-1769 pmol/L. The reference interval for men was 12-136 pmol/L and for postmenopausal women <26 pmol/L. CONCLUSIONS: The established estradiol reference intervals can be used for all traceable LC-MS/MS methods for medical-decision making.