Abstract
Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4–89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect.
Highlights
Osteoporosis is not a diagnostic feature of systemic lupus erythematosus (SLE), it commonly occurs secondary to medication, long-term glucocorticoids, and/or as a consequence of chronic inflammation
In this study we compared the ex vivo osteoclast differentiation capacities of monocytes derived from 72 individual SLE patients and 15 healthy controls (HC)
We investigated if mycophenolate mofetil (MMF) therapy affected osteoclast differentiation and found that in patients who were treated with MMF at the time-point of blood withdrawal, the mean osteoclast count was comparable to healthy controls
Summary
Osteoporosis is not a diagnostic feature of systemic lupus erythematosus (SLE), it commonly occurs secondary to medication, long-term glucocorticoids, and/or as a consequence of chronic inflammation. The differentiation, metabolism, growth and remodeling of bone is tightly regulated and balanced by osteoblasts, chondrocytes and osteoclasts. Osteoporosis occurs when this remodeling cycle gets unbalanced, with either increased osteoclast activity and/or reduced osteoblast function. Osteoblasts are derived from mesenchymal cells, whereas osteoclasts are derived from the mononuclear hematopoietic myeloid cell lineage and circulate as precursors through the blood stream. Differentiation of hematopoietic precursors into monocytes/macrophages has been shown to be intrinsically impaired in patients with SLE [1]. Crucial for osteoclast formation and regulation are the cytokines macrophage-colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), which are secreted by various cell types including osteoblasts [2]
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