Cytokines in Gaucher disease tied to early-onset osteoporosis in women
Specific inflammatory proteins may explain early bone density loss
Proteins called cytokines that are involved in regulating immune and inflammatory responses may help explain and track early-onset osteoporosis in women with Gaucher disease, a study reports.
Older women are typically most at risk of osteoporosis, a condition wherein bones become weak and are prone to fracture due to a disruption in a process called bone remodeling, which leads to a loss of bone mineral density (BMD). Early-onset BMD loss and osteoporosis are common in Gaucher disease. This study identifies several inflammatory cytokines that may contribute to osteoporosis arising at a younger age in this population.
“These findings not only expand our understanding of mechanisms of bone remodeling in [Gaucher disease], but also point toward novel biomarkers and therapeutic targets that may improve the management of bone health in females with [Gaucher disease],” the study’s researchers wrote. The study, “Age-related inflammatory biomarkers in early-onset osteoporosis in females with Gaucher disease,” was published in Frontiers in Endocrinology.
Mutations in the GBA1 gene, which contains instructions for cells to produce the enzyme glucocerebrosidase (GCase), cause Gaucher disease. Without functional GCase, a fatty molecule called glucocerebroside (Gb1) accumulates inside cells, particularly immune cells called macrophages. These Gb1-rich macrophages, also known as Gaucher cells, can infiltrate different organs and tissues, causing damage.
One potential area of infiltration is the spongy marrow inside bones. The resulting inflammation can increase the rate at which bone tissue is broken down while reducing the rate of bone regeneration, disrupting bone remodeling and leading to a net loss of BMD.
“Estrogen typically has a protective effect on bone density,” the researchers wrote, meaning most women don’t experience BMD loss until after menopause, when estrogen begins to decline. The detrimental effects of Gaucher disease on BMD can counteract the protective effects of estrogen, leading to earlier BMD loss.
Effect of inflammatory proteins on early-onset osteoporosis
“We hypothesize that the elevation of cytokines contributes to early-onset osteoporosis in female patients with [Gaucher disease] and could serve as biomarkers of bone pathology [disease],” wrote the researchers, who analyzed blood samples and clinical characteristics of 30 adult women with Gaucher disease and 22 healthy women. The participants were categorized based on age, with those younger than 45 being considered premenopausal and those older than 55 considered postmenopausal.
The researchers identified several cytokines whose levels differed between the groups, depending on factors that included age and bone health.
MIP-3-beta, a cytokine that helps attract immune cells to areas of inflammation, typically decreased with age in the healthy women. However, it was consistently higher in women with Gaucher disease, particularly in those older than 45 and in those with osteopenia, that is, low BMD and a possible early sign of osteoporosis, and osteoporosis. This indicates MIP-3-beta “may be a potential biomarker for BMD loss associated with aging in [Gaucher disease],” the researchers wrote.
Another inflammatory cytokine, MCP-1, showed signs of elevation in women with Gaucher disease, though this difference was only statistically significant compared with the healthy women using certain analysis methods. Elevated MCP-1 correlated with lower BMD regardless of age, so might contribute to the early onset of osteoporosis, including before menopause.
Two other cytokines, CCL27 and Eotaxin, also tended to be higher in women with Gaucher disease who had low BMD.
“Eotaxin levels were higher in patients with osteopenia and osteoporosis, with no significant differences between the two conditions, suggesting that Eotaxin might be involved in the initial phases of reduction in bone density and could be a promising option for the early detection of BMD loss,” the researchers wrote.
The results may help researchers understand the processes underlying BMD loss in women with Gaucher disease. Also, because cytokines may help drive BMD loss, they could serve as biomarkers and therapeutic targets in women with Gaucher disease.
“This study highlights the critical role of inflammation in the development of early-onset osteoporosis in females with [Gaucher disease], wrote the researchers, who noted that “targeting inflammation directly, alongside [other] therapies, could be key to managing osteoporosis in these patients.”
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