Comparative study of the synovial levels of RANKL and OPG in rheumatoid arthritis, spondyloarthritis and osteoarthritis

Quaresma, Thaíse Oliveira; Almeida, Sérgio Couto Luna de; Silva, Tarcília Aparecida da; Louzada Júnior, Paulo; Oliveira, Renê Donizeti Ribeiro de

doi:10.1186/s42358-023-00294-3

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Research • Adv. rheumatol. 63 • 2023 • https://doi.org/10.1186/s42358-023-00294-3 copy

Comparative study of the synovial levels of RANKL and OPG in rheumatoid arthritis, spondyloarthritis and osteoarthritis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction

In chronic arthropathies, there are several mechanisms of joint destruction. In recent years, studies have reported the implication of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in the process of activation and differentiation of osteoclasts, a key cell in the development of bone erosion. The RANKL/OPG ratio is increased in the serum of patients with malignant diseases and lytic bone disease, as well as rheumatoid arthritis (RA). The objective of this study was to measure and compare the concentrations of OPG and RANKL in the synovial fluid (SF) of patients with rheumatoid arthritis, spondyloarthritis (SpA) and osteoarthritis (OA).

Methods

This was an observational and cross-sectional study with 83 patients, 33 with RA, 32 with SpA and 18 with OA, followed up regularly in the outpatient clinics of the Rheumatology Department of the Clinics Hospital of the Ribeirão Preto Medical School-USP. All patients were assessed for indications for arthrocentesis by the attending physicians at the time of SF collection and were evaluated for demographic variables and medication use. Disease activity was assessed in individuals with RA and SpA. The quantification of SF OPG and RANKL levels was performed by ELISA, and the correlations of the results with clinical, laboratory and radiological parameters were assessed.

Results

We found no statistically significant difference in the RANKL and OPG levels among the groups. Patients with RA showed a positive correlation between the SF cell count and RANKL level (r = 0.59; p < 0.05) and the RANKL/ OPG ratio (r = 0.55; p < 0.05). Patients with OA showed a strong correlation between C-reactive protein (CRP) and the RANKL/OPG ratio (r = 0.82; p < 0.05). There was no correlation between the OPG and RANKL levels and markers of inflammatory activity or the disease activity index in patients with RA or SpA.

Conclusion

Within this patient cohort, the RANKL/OPG ratio was correlated with the SF cell count in patients with RA and with serum CRP in patients with OA, which may suggest a relationship with active inflammation and more destructive joint disease.

Keywords
Arthritides; Rheumatoid arthritis; Spondyloarthropathy; Osteoarthrosis; OPGL protein; RANKL protein

	Rheumatoid arthritis (n = 33)	Spondyloarthritis (n = 32)	Osteoarthritis (n = 18)	p-value
Demographics
Female [n (%)]	28 (85)	8 (25)	18 (100)	N/A
Age [years; median (IQR)]	57.0 (20–82)	46.5 (18–74)	68.0 (49–82)	N/A
Time of disease < 2 years [n (%)]	8 (24)	12 (37)	4 (22)	N/A
Comorbidities
Smoking [n (%)]	13 (40)	5 (15)	5 (28)	N/A
Cardiovascular diseases [n (%)]	21 (64)	13 (40)	12 (66)	N/A
Diabetes mellitus [n (%)]	2 (6)	3 (9)	3 (16)	N/A
Dyslipidemia [n (%)]	4 (12)	3 (9)	2 (11)	N/A
Obesity [n (%)]	4 (12)	2 (6)	5 (27)	N/A
Fibromyalgia [n (%)]	5 (15)	1 (3)	2 (11)	N/A
Laboratory findings
CRP [mg/dL; median (IQR)]	0.95 (0.4–3.1)	1.2 (0.6–6.3)	1.9 (0.5–3.4)	ns
CRP > 1.0 [mg/dL; n (%)]	16 (48)	17 (53)	10 (55)	ns
ESR [mm/h; median (IQR)]	23 (7–37)	19 (8–40.7)	20 (6–26)	ns
ESR > 20 [mm/h; n (%)]	18 (54.5)	15 (46.8)	7 (38.8)	ns
Cell count [/mm³; median (IQR)]	7675 (862–16950)	8400 (2475–16,825)	800 (250–1225)	< 0.01
Neutrophils [/mm³; median (IQR)]	77 (62–85)	72 (52–88)	70 (43–76)	ns
Medications
Methotrexate [n (%)]	8 (25)	2 (6)	–	ns
Leflunomide [n (%)]	8 (25)	1 (3)	–	ns
Sulfasalazine [n (%)]	1 (3)	5 (28)	–	ns
TNF-blocker [n (%)]	10 (30)	16 (50)	–	ns
Non TNF-blocker [n (%)]	6 (18)	1 (3)	–	ns

	RA (n = 33)		SpA (n = 32)		OA (n = 18)	p-value^* * ANOVA; SD Standard deviation
	DAS28 ≥ 3.2 (n = 15)	DAS28 < 3.2 (n = 18)	DAS28 ≥ 3.2 or ASDAS-CRP ≥ 2.1 (n = 14)	DAS28 < 3.2 or ASDAS-CRP < 2.1 (n = 18)	All patients (n = 18)
RANKL (pg/mL; mean ± SD)	85 ± 61	54 ± 31	66 ± 43	53 ± 24	65 ± 36	0.45
OPG (pg/mL; mean ± SD)	18,840 ± 11,460	14,800 ± 10,960	11,310 ± 12,160	21,250 ± 14,270	18,160 ± 11,040	0.16
RANKL/OPG (x10³)	38.6 ± 11.1	11.6 ± 10.4	16.7 ± 20.8	4.7 ± 5.3	5.6 ± 5.5	0.62

		RANKL	OPG	RANKL/ OPG
Rheumatoid arthritis
CRP	r^* * Spearman’s correlation; CRP C-reactive protein; For statistical significance (bold), p < 0.05	0.15	− 0.20	0.13
	p	0.51	0.26	0.54
Cell count	r	0.59	− 0.08	0.55
	p	0.004	0.68	0.008
Bone erosions	r	− 0.22	0.12	− 0.40
	p	0.37	0.52	0.09
DAS28	r	0.30	0.28	0.21
	p	0.12	0.14	0.28
Spondyloarthritis
CRP	r	0.01	− 0.13	0.18
	p	0.98	0.52	0.58
Cell count	r	− 0.11	0.22	− 0.09
	p	0.72	0.28	0.77
Bone erosions	r	0.30	− 0.19	0.20
	p	0.7	0.38	0.56
DAS28 or ASDAS-CRP	r	− 0.35	0.08	0.02
	p	0.054	0.79	0.89
Osteoarthritis
CRP	r	0.41	− 0.41	0.82
	p	0.28	0.17	0.006
Cell count	r	− 0.29	− 0.12	− 0.09
	p	0.48	0.71	0.83
Subchondral cysts or bone erosions	r	0.36	− 0.33	0.51
Subchondral cysts or bone erosions	p	0.25	0.20	0.09
Total
CRP	r	0.40	− 0.26	0.27
	p	0.008	0.025	0.08
Subchondral cysts or bone erosions	r	0.05	− 0.09	0.04
Subchondral cysts or bone erosions	p	0.74	0.74	0.78

Sociedade Brasileira de Reumatologia Av. Brigadeiro Luís Antônio, 2466, Jardim Paulista, 01402-000 - São Paulo, SP, Tel.: +551132897165 - São Paulo - SP - Brazil
E-mail: rbreumatol@terra.com.br

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[1] *Correspondence: Renê Donizeti Ribeiro de Oliveira, rdroliveira@hcrp.usp.br