TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease
Background and objective: 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 i...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/10/10/2217 |
| _version_ | 1797533307343208448 |
|---|---|
| author | Margarita Ivanova Julia Dao Lauren Noll Jacqueline Fikry Ozlem Goker-Alpan |
| author_facet | Margarita Ivanova Julia Dao Lauren Noll Jacqueline Fikry Ozlem Goker-Alpan |
| author_sort | Margarita Ivanova |
| collection | DOAJ |
| description | Background and objective: 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 in order to prevent irreversible complications. Methods: Thirty-three 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). The first GD cohort consisted of those with no bone complications (Z-score ≥ −0.9; T-scores ≥ −1), the second was the OSN group (−1.8 ≥ Z-score ≥ −1; −2.5 ≥ T-score ≥ −1), and the third was the 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. Results: TRAP5b levels were increased in GD patients, and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (lyso-Gb1) and macrophage activation markers CCL18 and chitotriosidase. The highest level of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Conclusion: TRAP5b, RANKL, and RANKL/OPG elevation indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities. |
| first_indexed | 2024-03-10T11:13:39Z |
| format | Article |
| id | doaj.art-e117f393dca84198a4e27354f5bc402b |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T11:13:39Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-e117f393dca84198a4e27354f5bc402b2023-11-21T20:38:43ZengMDPI AGJournal of Clinical Medicine2077-03832021-05-011010221710.3390/jcm10102217TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher DiseaseMargarita Ivanova0Julia Dao1Lauren Noll2Jacqueline Fikry3Ozlem Goker-Alpan4Lysosomal & Rare Disorders Research and Treatment Center, Fairfax, VA 22030, USALysosomal & Rare Disorders Research and Treatment Center, Fairfax, VA 22030, USALysosomal & Rare Disorders Research and Treatment Center, Fairfax, VA 22030, USALysosomal & Rare Disorders Research and Treatment Center, Fairfax, VA 22030, USALysosomal & Rare Disorders Research and Treatment Center, Fairfax, VA 22030, USABackground and objective: 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 in order to prevent irreversible complications. Methods: Thirty-three 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). The first GD cohort consisted of those with no bone complications (Z-score ≥ −0.9; T-scores ≥ −1), the second was the OSN group (−1.8 ≥ Z-score ≥ −1; −2.5 ≥ T-score ≥ −1), and the third was the 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. Results: TRAP5b levels were increased in GD patients, and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (lyso-Gb1) and macrophage activation markers CCL18 and chitotriosidase. The highest level of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Conclusion: TRAP5b, RANKL, and RANKL/OPG elevation indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities.https://www.mdpi.com/2077-0383/10/10/2217Gaucher diseaseosteoporosisTRAP5bOPGRANKLbiomarker |
| spellingShingle | Margarita Ivanova Julia Dao Lauren Noll Jacqueline Fikry Ozlem Goker-Alpan TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease Journal of Clinical Medicine Gaucher disease osteoporosis TRAP5b OPG RANKL biomarker |
| title | TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease |
| title_full | TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease |
| title_fullStr | TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease |
| title_full_unstemmed | TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease |
| title_short | TRAP5b and RANKL/OPG Predict Bone Pathology in Patients with Gaucher Disease |
| title_sort | trap5b and rankl opg predict bone pathology in patients with gaucher disease |
| topic | Gaucher disease osteoporosis TRAP5b OPG RANKL biomarker |
| url | https://www.mdpi.com/2077-0383/10/10/2217 |
| work_keys_str_mv | AT margaritaivanova trap5bandranklopgpredictbonepathologyinpatientswithgaucherdisease AT juliadao trap5bandranklopgpredictbonepathologyinpatientswithgaucherdisease AT laurennoll trap5bandranklopgpredictbonepathologyinpatientswithgaucherdisease AT jacquelinefikry trap5bandranklopgpredictbonepathologyinpatientswithgaucherdisease AT ozlemgokeralpan trap5bandranklopgpredictbonepathologyinpatientswithgaucherdisease |