Osteogenezis İmperfekta Hastalarında Kardiyovasküler Değerlendirme

Abstract

Osteogenesis imperfecta (OI) is the most common hereditary connective tissue disease of bone tissue, characterized by increased bone fragility, low bone mineral density and recurrent fractures. It is clinically and molecularly very heterogeneous. Clinical symptoms such as short stature, defective dentition, blue-gray sclera, hearing loss, lung problems and cardiac valve insufficiency may be observed. Type 1 collagen is an important component of various parts of the cardiovascular system, including the heart valves, chordae tendineae, fibrous rings of the heart, interventricular septum, aorta, and many other arteries. Studies have shown that there is an increased risk of cardiovascular disease in patients diagnosed with OI; However, there is not enough data on blood pressure characteristics. In this study, children diagnosed with OI who came for routine control at Hacettepe University Faculty of Medicine İhsan Doğramacı Children's Hospital Pediatric Endocrinology Polyclinic between November 2022 and August 2023 were evaluated in terms of cardiovascular and renal health. In addition to echocardiography, blood pressure characteristics were determined comprehensively by pulse wave velocity measurement and 24-hour ambulatory blood pressure measurement (ABPM), kidney functions were examined through urine and serum examinations, and the relationship between the detected characteristics and clinical and genetic features was aimed to be evaluated. 17 of the patients were girls (48.6%) and 18 (51.4%) were boys. The mean age at clinical diagnosis of OI was 27.94 ± 27.12 months; The median value was determined as 20 (1.0-101.0) months. Patients were grouped according to severity; 15 patients (42.9%) were evaluated as having the mild form known as type I OI, 13 patients (37.1%) as the moderate form known as type IV, and 7 patients (20.0%) as type III OI, known as the severe form. Eight patients (22.9%) had short stature; Short stature was detected in 71.4% of the severe OI group, and this frequency was 0% and 23.1% in the mild and moderate OI groups, respectively (p <0.001). Cumulative pamidronate dose differed according to disease groups (p=0.002); It was observed that the severe group received a higher cumulative dose than the mild and moderate groups. Proteinuria was detected at a statistically significantly higher rate in the severe OI group (57.1%) than in the mild OI group (7.1%) (p=0.047). In serum creatinine-based formulas, the estimated glomerular filtration rate (eGFR) value of the severe OI group was found to be higher, but there was no statistically significant difference. Considering that the severe OI group is more immobile and has lower muscle mass than the mild-moderate patients, serum creatinine-based eGFR evaluations may cause eGFR to be overestimated in patients with low muscle mass. When the left ventricular geometry of the patients was compared according to the severity of OI, a statistically significant difference was detected (p = 0.011); It was observed that this difference was between the severe and mild groups. Normal left ventricular geometry was found to be present in 84.6% of the mild OI group and 14.3% of the severe OI group. When the echocardiographic features of the patients were compared according to genetic features, the left ventricular mass index was higher in the COL1A1-2 related group and this difference was statistically significant (p = 0.045). When the pulse wave velocity values of the patients whose pulse wave velocity was measured were compared according to the severity of OI; Pulse wave velocity SDS levels (both according to age and height) were found to be higher in the moderate OI group than in the mild OI group (p<0.05). When the results of 18 patients who underwent ABPM were evaluated, hypertension was detected in a total of 4 patients (22%), 3 patients during the wakefulness period and 1 patient during the sleep period. When the dip values were examined, it was seen that in addition to 4 patients, 5 patients (33%) were "non-dipper". Nine patients (50%) had an abnormal ABPM profile, and office blood pressure measurements of these 9 patients were normal. It is important to monitor the blood pressure of OI patients in the pediatric age group and to closely follow children with cardiovascular warning signs. Intermittent ABPM may be useful in this patient group. Initiation of antihypertensive treatment in patients with hypertension detected by ABPM may reduce cardiovascular morbidity in later ages. By monitoring "non-dipper" patients, it can be determined whether these patients develop hypertension and its relationship with other organ damage. There is a need for further studies with a larger number of patients and long-term patient follow-up.