ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP118 | DOI: 10.1530/endoabs.63.GP118

Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher disease type 1

Anca Zimmermann1, Radu Popp2, Heidi Rossmann3, Simona Bucerzan4, Ioana Nascu4, Daniel Leucuta5, Matthias Weber1 & Paula Grigorescu-Sido4


1University Medical Center Mainz, 1. Med. Clinic, Department of Endocrinology and Metabolic Diseases, Mainz, Germany; 2University of Medicine and Pharmacy Iuliu Hatieganu, Department of Medical Genetics, Cluj, Romania; 3University Medical Center Mainz, Institute for Clinical Chemistry and Laboratory Medicine, Mainz, Germany; 4University of Medicine and Pharmacy Iuliu Hatieganu, Center of Genetic Diseases, 1st Pediatric Clinic, Cluj, Romania; 5University of Medicine and Pharmacy Iuliu Hatieganu, Department of Medical Informatics and Biostatistics, Cluj, Romania.


Purpose: Osteopathy/osteoporosis in Gaucher disease type 1 (GD1) shows variable responses to enzyme replacement therapy (ERT); the pathogenesis is incompletely understood. We aimed to investigate the effect of several gene variants on bone mineral density (BMD) and serum markers of bone metabolism in GD1.

Patients/methods: 50 adult Caucasian patients with GD1/117 controls were genotyped for gene variants in the osteoprotegerin (TNFRSF11B; OPG), estrogen receptor alpha (ESR1), calcitonin receptor (CALCR), vitamin D receptor (VDR) genes. In patients and 50 matched healthy controls, we assessed: clinical data, serum markers of bone metabolism, subclinical inflammation. BMD was measured for the first time before/during ERT (median 6.7 years).

Results: 42% of patients were splenectomized. ERT led to variable improvements in BMD. Distribution of gene variants was comparable between patients/controls. The AA genotype (c.1024+283G>A gene variant; VDR gene) was associated with lower Z scores before ERT vs. GA (P=0.033), was encountered in 82.3% of patients with osteoporosis and was more frequent in patients with pathological fractures. Z score increases during ERT were higher in patients with the CC genotype (c.9C>G variant, TNFRSF11B; OPG gene) compared to GC (P=0.003). The CC genotype (c.1340T>C variant, CALCR gene) was associated with higher Z scores before ERT than the TT genotype (P=0.041) and was absent in osteoporosis. Osteocalcin and osteoprotegerin were lower in patients vs. controls; beta crosslaps, interleukin-6, ferritin were higher.

Conclusions: We suggest for the first time a protective role against osteoporosis in GD1 patients for the CC genotype of the c.9C>G gene variant in the TNFRSFB11 (OPG) gene and for the CC genotype of the c. 1340T>C gene variant (CALCR gene), while the AA genotype of the c.1024+283G>A gene variant in the VDR gene appears as a risk factor for lower BMDs. Serum markers suggest decreased osteosynthesis, reduced inhibition of osteoclast activation, increased bone resorption and subclinical inflammation during ERT.