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Abstract

Background

Low disease activity state (LDAS) has been linked to a significant reduction in flares and damage accrual in patients with systemic lupus erythematosus (SLE); however, the effect of LDAS on the risk of vertebral fractures (VFs) in subjects with SLE is unknown, considering that low bone mineral density (BMD) and VF are frequent in SLE.

Objective

to evaluate whether achieving LDAS ≥50% of the observation time prevents new VF and BMD changes in Mestizo women.

Methods

We carried out a longitudinal, observational, and retrospective study. Mestizo women with SLE were included for a median of an 8-year follow-up. LDAS was described as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4, prednisone ≤7.5 mg/day, and stable immunosuppressive therapies. BMD measurements and lateral thoracic and lumbar radiographs for a semiquantitative analysis for VF were assessed at baseline and during the follow-up. Uni- and multivariable interval-censored survival regression models were carried out.

Results

We included 110 patients: 35 (31.8%) had new VF. A total of 56 patients (50.1%) achieved LDAS ≥50% of the time during the follow-up and achieved a significantly lesser risk of incident VF (HR = 0.16; 95% CI, 0.06–0.49). After adjusting by age, BMI, menopause, prevalent VF, baseline BMD, cumulative glucocorticoid use, and anti-osteoporotic therapy, LDAS-50 was significantly related to a decrease in the risk of a new VF (HR = 0.39; 95% CI, 0.16–0.98). There was no association between LDAS and BMD measurement changes. When only patients on LDAS but not in remission (n = 43) were evaluated for the risk of incident VF, both uni- and multivariate analyses were significant (HR = 0.12; 95 CI, 0.04–47; p = 0.001, and HR = 0.26; 95% CI, 0.7–0.88; p = 0.03).

Conclusions

LDAS ≥50% of the time was significantly associated with a diminished risk of new VF in Mestizo women with SLE, even in patients not in remission. However, LDAS did not help modify BMD changes over time.

Keywords

Systemic lupus erythematosus incident vertebral fractures bone mineral density low disease activity

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References

Dorner

Furie

. Novel paradigms in systemic lupus erythematosus. Lancet 2019; 393: 2344–2358.

Jorge

Zhang

, et al. Unchanging premature mortality trends in systemic lupus erythematosus: a general population-based study (1999–2014). Rheumatol 2018; 57: 337–344.

Chambers

Allen

Rahman

, et al. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatol 2009; 48: 673–675.

Parra-Sánchez

Voskuyl

van Vollenhoven

. Treat-to-target in systemic lupus erythematosus: advancing towards its implementation. Nat Rev Rheumatol 2022; 18: 146–157.

van Vollenhoven

Bertsias

Doria

, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus Sci Med 2021; 8: e000538.

Petri

Magder

. Comparison of Remission and Lupus Low Disease Activity State in Damage Prevention in a United States Systemic Lupus Erythematosus Cohort. Arthritis Rheumatol 2018; 70: 1790–1795.

Sharma

Raymond

Eilertsen

, et al. Association of Achieving Lupus Low Disease Activity State Fifty Percent of the Time With Both Reduced Damage Accrual and Mortality in Patients With Systemic Lupus Erythematosus. Arthritis Care Res 2020; 72: 447–451.

Mwp

T-A-S

Bultink

IEM

Heslinga

, et al. Both prolonged remission and Lupus Low Disease Activity State are associated with reduced damage accrual in systemic lupus erythematosus. Rheumatol 2017; 56: 121–128.

Zen

Iaccarino

Gatto

, et al. Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission. Ann Rheum Dis 2018; 77: 104–110.

10.

Ugarte-Gil

Gamboa-Cardenas

Reátegui-Sokolova

, et al. LLDAS (lupus low disease activity state) and/or remission are associated with less damage accrual in patients with systemic lupus erythematosus from a primarily Mestizo population: data from the Almenara Lupus Cohort. Lupus Sci Med 2022; 9: e000616.

11.

Harvey

Dennison

Cooper

. Osteoporosis: impact on health and economics. Nat Rev Rheumatol 2010; 6: 99–105.

12.

Oleksik

Lips

Dawson

, et al. Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures. J Bone Miner Res 2000; 15: 1384–1392.

13.

Hasserius

Karlsson

Jónsson

, et al. Long-term morbidity and mortality after a clinically diagnosed vertebral fracture in the elderly--a 12- and 22-year follow-up of 257 patients. Calcif Tissue Int 2005; 76: 235–242.

14.

Mendoza-Pinto

Rojas-Villarraga

Molano-González

, et al. Bone mineral density and vertebral fractures in patients with systemic lupus erythematosus: a systematic review and meta-regression. PLoS One 2018; 13: e0196113.

15.

Rentero

Amigo

Chozas

, et al. Prevalence of fractures in women with rheumatoid arthritis and/or systemic lupus erythematosus on chronic glucocorticoid therapy. BMC Muscoskel Disord 2015; 16: 300.

16.

Kim

Rowe

Raymond

, et al. Underreporting of vertebral fractures on routine chest radiography. AJR Am J Roentgenol 2004; 182: 297–300.

17.

Bultink

IEM

Lems

Kostense

, et al. Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus. Arthritis Rheum 2005; 52: 2044–2050.

18.

Bultink

IEM

. Bone Disease in Connective Tissue Disease/Systemic Lupus Erythematosus. Calcif Tissue Int 2018; 102: 575–591.

19.

Mendoza-Pinto

García-Carrasco

Juárez-Melchor

, et al. A Retrospective Analysis of Longitudinal Changes in Bone Mineral Density in Women with Systemic Lupus Erythematosus. Calcif Tissue Int 2021; 109: 363–371.

20.

Schmajuk

Yelin

Chakravarty

, et al. Osteoporosis screening, prevention, and treatment in systemic lupus erythematosus: application of the systemic lupus erythematosus quality indicators. Arthritis Care Res 2010; 62: 993–1001.

21.

Dirven

van den Broek

van Groenendael

JHLM

, et al. Prevalence of vertebral fractures in a disease activity steered cohort of patients with early active rheumatoid arthritis. BMC Muscoskel Disord 2012; 13: 125.

22.

Wysham

Shofer

Lui

, et al. Low cumulative disease activity is associated with higher bone mineral density in a majority Latinx and Asian US rheumatoid arthritis cohort. Semin Arthritis Rheum 2022; 53: 151972.

23.

Tan

Cohen

Fries

, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

24.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.

25.

Holick

. Vitamin D deficiency. N Engl J Med 2007; 357: 266–281.

26.

Ugarte-Gil

Wojdyla

Pons-Estel

, et al. Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL). Ann Rheum Dis 2017; 76: 2071–2074.

27.

García-Carrasco

Mendoza-Pinto

León-Vázquez

, et al. Incidence of Vertebral Fractures in Women with Systemic Lupus Erythematosus After 8 Years of Follow-Up. Calcif Tiss Int Tissue Int 101. Epub ahead of print 2017. DOI: 10.1007/s00223-017-0286-z.

28.

Genant

van Kuijk

, et al. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993; 8: 1137–1148.

29.

Smith

EMD

Tharmaratnam

Al-Abadi

, et al. Attainment of Low Disease Activity and Remission Targets reduces the risk of severe flare and new damage in Childhood Lupus. Rheumatology 2021; 61: 3378–3389.

30.

Hao

Gao

, et al. Flare rates and factors determining flare occurrence in patients with systemic lupus erythematosus who achieved low disease activity or remission: results from a prospective cohort study. Lupus Sci Med 2022; 9: e000553.

31.

Piga

Floris

Cappellazzo

, et al. Failure to achieve lupus low disease activity state (LLDAS) six months after diagnosis is associated with early damage accrual in Caucasian patients with systemic lupus erythematosus. Arthritis Res Ther 2017; 19: 247.

32.

Tani

Vagelli

Stagnaro

, et al. Remission and low disease activity in systemic lupus erythematosus: an achievable goal even with fewer steroids? Real-life data from a monocentric cohort. Lupus Sci Med 2018; 5: e000234.

33.

Ugarte-Gil

Mendoza-Pinto

Reátegui-Sokolova

, et al. Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: a systematic literature review. Lupus Sci Med 2021; 8: e000542.

34.

Ji-Won

Ju-Yang

Hyoun-Ah

, et al. Lupus Low Disease Activity State Achievement Is Important for Reducing Adverse Outcomes in Pregnant Patients With Systemic Lupus Erythematosus. J Rheumatol 2021; 48: 707–716.

35.

Golder

Kandane-Rathnayake

Hoi

AY-B

, et al. Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study. Arthritis Res Ther 2017; 19: 62.

36.

Louthrenoo

Kasitanon

Morand

, et al. Comparison of performance of specific (SLEQOL) and generic (SF36) health-related quality of life questionnaires and their associations with disease status of systemic lupus erythematosus: a longitudinal study. Arthritis Res Ther 2020; 22: 8.

37.

Emamikia

Oon

Gomez

, et al. Impact of remission and low disease activity on health-related quality of life in patients with systemic lupus erythematosus. Rheumatol 2022; 61: 4752–4762.

38.

Kravvariti

Konstantonis

Sfikakis

, et al. Progression of subclinical atherosclerosis in systemic lupus erythematosus versus rheumatoid arthritis: the impact of low disease activity. Rheumatol 2018; 57: 2158–2166.

39.

Ehresman

Schilling

Yang

, et al. Vertebral bone quality score predicts fragility fractures independently of bone mineral density. Spine J 2021; 21: 20–27.

40.

Schuit

SCE

van der Klift

Weel

AEAM

, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 2004; 34: 195–202.

41.

Epsley

Tadros

Farid

, et al. The Effect of Inflammation on Bone. Front Physiol 2020; 11: 511799.

42.

Weinstein

. Glucocorticoid-Induced Bone Disease. N Engl J Med 2011; 365: 62–70.

43.

Dalle Carbonare

Arlot

Chavassieux

, et al. Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res 2001; 16: 97–103.

44.

Tang

Qin

Kwok

, et al. Alterations of bone geometry, density, microarchitecture, and biomechanical properties in systemic lupus erythematosus on long-term glucocorticoid: a case-control study using HR-pQCT. Osteoporos Int 2013; 24: 1817–1826.

45.

Alarcon

Ugarte-Gil

Pons-Estel

, et al. Remission and low disease activity state (LDAS) are protective of intermediate and long-term outcomes in SLE patients. Results from LUMINA (LXXVIII), a multiethnic, multicenter US cohort. Lupus 2019; 28: 423–426.

46.

Zen

Iaccarino

Gatto

, et al. The effect of different durations of remission on damage accrual: results from a prospective monocentric cohort of Caucasian patients. Ann Rheum Dis 2017; 76: 562–565.

47.

Gao

Hao

, et al. Frequencies and predictors of the Lupus Low Disease Activity State and remission in treatment-naïve patients with systemic lupus erythematosus. Rheumatol 2020; 59: 3400–3407.

48.

Kandane-Rathnayake

Golder

Louthrenoo

, et al. Development of the Asia Pacific Lupus Collaboration cohort. Int J Rheum Dis 2019; 22: 425–433.

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Low disease activity state associated with fewer incident vertebral fractures in Mestizo women with systemic lupus erythematosus

Abstract

Background

Objective

Methods

Results

Conclusions

Keywords

Get full access to this article

References

Supplementary Material