ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Bone Research
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1606218
Age-related inflammatory biomarkers in early-onset osteoporosis in females with Gaucher disease
Provisionally accepted
- Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, United States
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Gaucher disease (GD), the most common lysosomal disorder, is caused by a deficiency of the enzyme glucocerebrosidase (GCase). Accumulation of the substrate, glycosylceramide (Gb-1), and its lysosomal derivative, glucosylsphingosine, Lyso-Gb1, are associated with immune-mediated inflammation. Patients with GD experience progressive bone disease, including early-onset osteoporosis (OSR). Bone marrow infiltration with Gaucher cells and reduced bone mineral density (BMD) suggest that glycosphingolipids affect hematopoiesis, osteoclast differentiation and activity. Unlike the general population, where osteoporosis is a concern later in life, females with GD have an increased risk of BMD loss starting from adolescence, which is further impacted by pregnancy, breastfeeding, and menopause. The study's aim was to investigate immune and inflammatory markers, focusing on early-onset osteoporosis in females. GD females and healthy controls were categorized by age: pre-menopause (<45), 45-55, and post-menopause (55+), and were further divided into three sub-cohorts: no bone complications, osteopenia (OSN), and osteoporosis (OSR). The Luminex Cytokine-96-Plex panel analysis identified 26 elevated cytokines. CD40L, APRIL, IL-35, and MIP-3β were correlated with age in healthy females but were elevated in all age categories in GD. Increased levels of Eotaxin, MCP-1, and CCL27 (CTACK) correlated with OSR. Furthermore, the age-related macrophage inflammatory protein (MIP-3β) was associated with BMD loss in female patients with GD.Conclusion: Chronic inflammation and the continuous release of cytokines related to immune aging are significant determinants for the development of early-onset osteoporosis in female patients with GD. Osteoporosis in GD illustrates the pivotal role of immune-mediated inflammation in bone resorption.This study highlights that the ongoing release of cytokines associated with immune aging may contribute to early-onset osteoporosis in GD. By identifying age-and disease-specific cytokine signatures, including elevated levels of CD40L, APRIL, MCP-4, Eotaxin, STACK, and MIP-3β, we propose a pathophysiological link between inflammation and early-onset osteoporosis in female patients with GD.
Keywords: Gaucher Disease, Women's Health, age, Osteoporosis, Cytokines, Inflammation
Received: 04 Apr 2025; Accepted: 10 Jun 2025.
Copyright: © 2025 Ivanova, Dao, Kasaci, Huang, Nguyenn and Goker-Alpan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Margarita M Ivanova, Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, United States
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