Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Pietschmann, Péter; Butylina, Maria; Kerschan‐Schindl, Katharina; Sipos, Wolfgang

doi:10.3390/ijms23158740

Cited by 20 publications

(15 citation statements)

References 112 publications

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“…The relation between RA and osteoporosis is not clearly identified 22 . In the current study, patients with osteoporosis constituted 39.58%, there were no statistically significant differences between patients with and without osteoporosis regarding clinical and laboratory disease characteristics.…”

Section: Discussioncontrasting

confidence: 69%

Cartilage and bone loss in premenopausal women with rheumatoid arthritis: Radiological and laboratory assessments

Elsawy,

Ghazala,

Elnemr

2023

Int J of Rheum Dis

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IntroductionTo investigate the radiological and laboratory features of bone and cartilage losses in premenopausal women with rheumatoid arthritis (RA).MethodsThis case–control study is the continuation of a study that was conducted on 48 women with RA and 48 matched healthy volunteers. All RA patients were previously subjected to clinical examination, disease activity assessment using the 28‐joint Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI), serological tests, dual‐energy X‐ray absorptiometry measuring bone mineral density (BMD), and plain X‐ray of both hands. Added to these, matrix metalloproteinase 3 (MMP‐3) and cartilage oligomeric matrix protein (COMP) were measured by enzyme‐linked immunosorbent assay.ResultsThere were statistically significant differences between patients and controls regarding COMP and MMP‐3, being higher in patients (p < .001). COMP and MMP‐3 have significant positive correlation with serum levels of anti‐cyclic citrullinated peptide (anti‐CCP) and anti‐carbamylated protein (anti‐CarP). The original Sharp erosion score was positively correlated with the serum level of the studied antibodies and disease duration, but no significant correlation was found with either COMP, MMP‐3, or DAS‐28. Spine BMD and Z score were negatively correlated with disease activity and anti‐CarP. There were significant positive relationhsips between indices of local cartilage and bone loss and the indices of systemic bone loss. MMP‐3 had no correlation with indices of local cartilage and bone loss and disease activity scores.ConclusionsThe pathogenic mechanism of hand joint damage involved the three studied autoantibodies namely, rheumatoid factor, anti‐CCP and anti‐CarP antibodies. Anti‐CarP antibody was involved in the reduction of BMD of the spine. The association between systemic osteoporosis and hand joint damage pointed to a common pathogenic mechanism.

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Section: Discussioncontrasting

confidence: 69%

Cartilage and bone loss in premenopausal women with rheumatoid arthritis: Radiological and laboratory assessments

Elsawy,

Ghazala,

Elnemr

2023

Int J of Rheum Dis

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“…Located on chromosome 3, ZIC1 is a known meningeal identity gene. Studies have shown that ZIC1 promoter methylation was related to the etiology of postmenopausal osteoporosis [16], and patients with RA are at high risk of osteoporosis [17–20]. Our findings suggest that ZIC1 may be associated with RA susceptibility, and deserve further in‐depth research.…”

Section: Resultsmentioning

confidence: 55%

Identification of novel meQTLs strongly associated with rheumatoid arthritis by large‐scale epigenome‐wide analysis

Tang

Sun

et al. 2022

FEBS Open Bio

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Rheumatoid arthritis (RA) is highly heritable, and previous studies have suggested that genetic variation may affect susceptibility to RA by altering epigenetic modifications (e.g. DNA methylation). Here we examined how genetic variation influences DNA methylation (DNAm) in RA by integrating individual genetic variation and DNAm data. Epigenome‐wide meQTL (methylation quantitative trait loci) analysis was performed on 354 RA patients and 335 controls, scanning 30,101,744 relationships between 62 SNPs and 485,512 DNA methylation sites. Two regulatory relationship pairs (FDR < 0.05) showed very strong associations with RA risk. One was rs10796216‐cg00475509, and the DNAm decreased by 0.0168 per addition of allele rs10796216‐A. The other was rs6546473‐cg13358873, for which a 0.0365 reduction of DNAm at cg13358873 was observed for each addition of allele rs6546473‐A, and lower DNAm was found to be significantly associated with RA risk (P = 2.0407e‐28). Moreover, both pairs of meQTL showed a strong regulatory relationship only in RA samples, so they can be subsequently considered as risk markers for RA. In conclusion, our integrated analysis of genetic and epigenetic variation suggests that genetic variation may affect the risk of RA by regulating DNA methylation levels. Alterations of DNAm at cg00475509 and cg13358873 loci conferred by rs10796216‐A and rs6546473‐A allele may suggest a potential risk for RA. Our results deepen our understanding of the genetic and epigenetic mechanisms of RA and provide novel associations that can be further investigated in future studies.

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“…Proposed risk factors such as aging, estrogen deficiency, systemic inflammation, reduced mobility, glucocorticoid treatment, and sarcopenia are associated with the pathophysiology of osteoporosis or its related fractures. [30] Inflammation has an adverse effect on BMD and it appears to be related to the activation of osteoclasts due to upregulation of osteoclastogenic cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and IL-17, during inflammatory processes. Several studies have suggested that treatment with biologic DMARDs is associated with a reduction in bone loss.…”

Section: Discussionmentioning

confidence: 99%

The comparable efficacy of denosumab on bone mineral density in rheumatoid arthritis patients with postmenopausal osteoporosis: A retrospective case-control study

Kim

Lee

et al. 2023

Medicine

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Little is known about differences in the therapeutic efficacy of denosumab in subjects with and without rheumatoid arthritis (RA). This study compares the changes in bone mineral density (BMD) between RA patients and controls without RA who had been treated with denosumab for 2 years for postmenopausal osteoporosis. A total of 82 RA patients and 64 controls were enrolled, who were refractory to selective estrogen receptor modulators (SERMs) or bisphosphonates and completed the treatment of denosumab 60 mg for 2 years. The efficacy of denosumab in RA patients and controls was assessed using areal BMD (aBMD) and T-score of the lumbar spine, femur neck, and total hip. A general linear model with repeated measures analysis of variance was used to determine differences in aBMD and T-score between 2 study groups. No significant differences in percent changes in aBMD and T-scores by denosumab treatment for 2 years at the lumbar spine, femur neck, and total hip were evident between RA patients and controls (P > .05 of all), except T-score of the total hip (P = .034). Denosumab treatment equally increased aBMD at the lumbar spine and T-scores at the lumbar spine and total hip between RA patients and controls without statistical differences, but RA patients showed less improvement in aBMD at the femur neck (p time*group = 0.032) and T-scores at the femur neck and total hip than controls (p time*group = 0.004 of both). Changes in aBMD and T-scores after denosumab treatment in RA patients were not affected by previous use of bisphosphonates or SERMs. Differences of T-score at the femur neck among previous bisphosphonate users and aBMD and T-score at the femur neck and T-scores at the total hip were evident. This study revealed that 2 years of denosumab treatment in female RA patients achieved comparable efficacy on BMD to controls at the lumbar spine, but showed somewhat insufficient improvement at the femur neck and total hip.

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Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis

Cited by 20 publications

References 112 publications

Cartilage and bone loss in premenopausal women with rheumatoid arthritis: Radiological and laboratory assessments

Cartilage and bone loss in premenopausal women with rheumatoid arthritis: Radiological and laboratory assessments

Identification of novel meQTLs strongly associated with rheumatoid arthritis by large‐scale epigenome‐wide analysis

The comparable efficacy of denosumab on bone mineral density in rheumatoid arthritis patients with postmenopausal osteoporosis: A retrospective case-control study

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