Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher disease

Version 1 : Received: 15 April 2021 / Approved: 17 April 2021 / Online: 17 April 2021 (08:49:25 CEST)

A peer-reviewed article of this Preprint also exists.

Ivanova, M.; Dao, J.; Noll, L.; Fikry, J.; Goker-Alpan, O. TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease. J. Clin. Med. 2021, 10, 2217. Ivanova, M.; Dao, J.; Noll, L.; Fikry, J.; Goker-Alpan, O. TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease. J. Clin. Med. 2021, 10, 2217.

Journal reference: J. Clin. Med. 2021, 10, 2217
DOI: 10.3390/jcm10102217

Abstract

Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus early diagnosis is crucial for identifying high-risk patients to prevent irreversible complications. Thirty-one patients with GD were assessed prospectively to identify predictive markers associated with bone density abnormalities, osteopenia (OSN), and osteoporosis (OSR). Subjects were categorized into three cohorts based on T- or Z- scores of bone mineral density (BMD): In GD cohort with no bone complication (Z-score≥-0.9; T-scores≥-1), the OSN group (-1.8 ≥ Z-score ≥ -1; -2.5 ≥ T-score ≥ -1) and OSR group (Z-score ≤ -1.9; T-scores ≤ -2.5). Serum levels of TRAP5b, RANKL, OPG, and RANK were quantified by enzyme-linked immunosorbent assays. TRAP5b was increased in GD and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (Lyso-Gb1), macrophage activation markers CCL18 and chitotriosidase. The highest levels of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Elevation of TRAP5b, RANKL, and RANKL/OPG indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities.

Keywords

Gaucher disease; Osteoporosis; TRAP5b; OPG; RANKL; biomarker; Lyso-Gb1; inflammation

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