Association between bone mineral density and hearing loss in Osteogenesis Imperfecta
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1 Association between bone mineral density and hearing loss in Osteogenesis Imperfecta F Swinnen 1 E De Leenheer 1 S Goemaere 2 P Coucke 3 C Cremers 4 I Dhooge 1 (1) Departement of Otorhinolaryngology, Ghent University (Hospital) (2) Department of Endorinology & Rheumatology, Unit Osteporosis & Metabolic Bone Diseases, Ghent University Hospital (3) Center for Medical Genetics, Ghent University Hospital (4) Department of Otorhinolaryngology, Radboud University Nijmegen Medical Center
2 I. Introduction Osteogenesis Imperfecta (OI) - Hearing loss 2/16 50 % of OI patients OI types I, III, IV Mild to profound hearing loss, progressive Intrafamilial variability Hearing loss type: Conductive hearing loss Mixed hearing loss Pure high-frequency sensorineural hearing loss Pure sensorineural hearing loss
3 I. Introduction OI - Hearing loss (2) Mixed hearing loss 3/16 Conductive hearing loss Sensorineural hearing loss
4 I. Introduction OI - Hearing loss (3) 4/16 Conductive Mixed Pure sensorineural loss Otosclerosis-like lesions: stapes footplate fixation (and pericochlear lesions) Cochlear hair cell atrophy Atrophy stria vascularis Ossicular discontinuity (fractured/atrophic ossicles) Perilymphe hemorrhage
5 I. Introduction Computed tomography temporal bones 5/16 Bilaterally severely progressed mixed hearing loss in a 67-year old OI-patient: severe pericochlear demineralization of bone
6 I. Introduction Research aim 6/16 Relationship between occurrence/type of hearing loss and generalized bone disease? Heterogeneity of hearing loss explained by variability in bone characteristics?
7 II. Methods Patients and materials 7/16 56 adult OI patients (F: 34 M: 22) with identified mutation in COL1A1 or COL1A2 Mean age: 43 y. (SD 13.7) Bisphosphonates administration excluded Audiological evaluation Pure-tone audiometry Admittance measurements Stapedius reflex measurements Bone mineral density (BMD) measurements
8 II. Methods Bone mineral density measurements Dual X-ray absorptiometry (DXA): areal BMD (abmd) Lumbar spine trabecular bone abmd 8/16 Whole body cortical bone abmd Peripheral quantitative computed tomography (pqct): volumetric BMD (vbmd) Radial metaphysis (4%) trabecular bone vbmd Radial diaphysis (66%) cortical bone vbmd 4% 66% bone geometry parameters: cortical thickness, periosteal circumference, endosteal circumference
9 III. Results Audiological phenotype 9/ % 46% 14%
10 III. Results Hearing loss as a function of OI type and genotype in 56 OI patients 10/16 sensorineural conductive/mixed normal COL1A1 COL1A1 COL1A2 quantitative qualitative qualitative 0 OI type I OI type IV No association between hearing loss and mutated gene, type I collagen defect or OI type
11 abmd Z- score III. Results Hearing loss as a function of abmd (DXA) 11/16 DXA Lumbar spine DXA Whole body Normal Conductive/ mixed Normal Conductive/ mixed Sensorineural Sensorineural (N=19) (N=29) (N=8) (N=19) (N=29) (N=8) Mean z-scores < 0 (except sensorineural losses) ANCOVA [gender, weight, type I collagen defect] : sensorineural hearing loss > conductive/mixed hearing loss and normal hearing (P<0.05)
12 Trabecular vbmd Z- score III. Results Hearing loss as a function of vbmd (pqct) Cortical vbmd (mg/mm 3 ) 12/16 pqct radial metaphysis: trabecular bone pqct radial diaphysis: cortical bone Normal Conductive/ mixed Normal Conductive/ mixed ANCOVA [gender, age, type I collagen defect] for (trabecular vbmd z-score *hearing): conductive/mixed hearing loss < normal and sensorineural hearing loss Radial diaphysis: no differences in cortical vbmd or bone geometry parameters Sensorineural Sensorineural (N=19) (N=29) (N=8) (N=19) (N=29) (N=8)
13 III. Results Between-relatives comparisons of BMD and hearing 13/16 Family number Family number OI patients with conductive/mixed hearing loss have lower BMD compared to their normal hearing relatives with OI
14 IV. Discussion 14/16 OI patients with conductive/mixed hearing loss have lower BMD than patients with normal hearing or pure sensorineural loss OI patients with pure sensorineural hearing loss have higher abmd than patients with normal hearing or conductive/mixed hearing loss (small sample + highest mean age) No differences in volumetric cortical bone mineral density or bone geometry parameters measured at radial diaphysis:! Cortical vbmd: unreliable parameter when cortical thickness < 2.0 mm (spatial resolution too low)
15 V. Discussion 15/16 Temporal bone: Cortical bone Bone formation complete at age 1 year Bone remodeling is minimal Association conductive/mixed hearing loss and lower BMD: accumulating microfractures and fatigue microdamage destruct the osteoprotegerin (OPG) pathways which regulate temporal bone remodeling inhibition? Future perspectives: Replication in large population Histological investigations of OI temporal bones Effects of bisphosphonates on hearing in OI
16 16/16
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