Background/Purpose: Rheumatoid arthritis (RA) is characterised by progressive joint destruction and periarticular bone loss. In RA patients with insufficient response to Disease-Modifying Anti-rheumatic drugs (DMARDs) treated in clinical practice tumour necrosis factor inhibitors(TNFi) retard the joint damage(1), but their impact on hand bone loss and predictors thereof are not known. The aim of this study was to compare hand bone changes during treatment with Disease-Modifying Anti-rheumatic drugs (DMARDs) and subsequent treatment with TNFi in RA patients in clinical practice, and investigate the association between radiographic progression and hand bone loss. Furthermore, to identify predictors of hand bone loss during TNFi treatment in clinical practice.

Methods: X-rays of hands were obtained ~2 yrs before start of TNFi(pre-baseline), at the start of TNFi(baseline) and ~ 2 yrs after(follow-up). Clinical data from the DANBIO registry and patient files were collected. Hand x-rays were scored blinded to chronology according to the Sharp/van der Heijde method. Hand bone mineral density (BMD) was estimated with Digital X-ray Radiogrammetry(DXR), a computerised method to measure cortical bone thickness of the 2^nd – 4^th metacarpal. Annual (absolute and relative) hand BMD loss and radiographic progression rates during DMARD and TNFi treatment were calculated. Potential predictive baseline variables were investigated with univariate regression and significant variables included in a multiple linear regression analysis with annual BMD loss during TNFi treatment as the dependent variable.

 

Results: 136 RA patients (85% women, 71% rheumatoid factor positive, age 55(23-84) years(median (range)); disease duration 5(1-53) years) had three x-rays suitable for DXR. Pre-baseline 28 joint disease activity score(DAS28) was 4.3(1.6-6.9). At baseline DAS28 was 5.3(1.4-8.2) and infliximab(74%), etanercept(13%), or adalimumab(13%) was started. At follow-up, 59% were on initial TNFi, 27% had switched to another TNFi and 14% had withdrawn. DAS28 was 3.1(1.4-7.7). Data on BMD loss and radiographic progression are shown in Table 1. Patients with radiographic progression (change in Total Sharp Score >0) had higher BMD loss than patients without radiographic progression in both the DMARD (-0.94 mg/cm² (median) vs. -0.54, p = 0.03, Wilcoxon) and TNFi period (-0.74 vs. 0.34, p = 0.004, Wilcoxon). Independent predictors of BMD loss during the TNFi period were: higher age (-0.2mg/cm²/10 year increase) and 28 swollen joint count (SJC) (-0.4mg/cm²/joint increase).

 

	BMD and radiographic status			Annual change in BMD and TSS
	Prebaseline X-ray	Baseline X-ray	Follow-up X-ray	DMARD period	TNFi period	P-value (1)
TSS median (IQR), units	6 (0-21)	10 (1-29)	12 (2-31)	0.6 (0.0-2.5)	0.0 (0.0-0.8)	< 0.0001
BMD median (IQR), g/cm2	0.55 (0.48-0.61)	0.53 (0.45-0.59)	0.52 (0.44-0.57)	-0.0079 (-0.017- -0.002)	-0.0047 (-0.012 – -0.001)	0.001
BMD median (IQR), %				– 1.55 (-3.45- -0.44)	-1.11 (-2.52- -0.15)	0.02
Correlation TSS vs. BMD (2)	– 0.45	– 0.45	– 0.43	– 0.23	– 0.27
P-value (2)	<0.0001	<0.0001	<0.0001	0.0007	0.001
1Wilcoxon Signed Rank 2Spearman. The DMARD period is the period between pre-baseline and baseline X-rays, while the TNFi period is the period between baseline and follow-up X-rays. TSS, Total Shap Score (of hands); BMD, Bone Mineral Density

Conclusion: In 136 established RA patients TNFi treatment reduced BMD loss and radiographic progression. High age and SJC predicted BMD loss during TNFi treatment. During DMARD- and TNFi treatment radiographic progression and BMD loss were moderately correlated.

 References: (1)Ørnbjerg LM. Ann Rheum DisPublished Online First: 24 April 2012. doi: 10.1136/annrheumdis-2012-201319

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-tumour-necrosis-factor-inhibitor-treatment-on-hand-bone-loss-in-rheumatoid-arthritis-patients-treated-in-clinical-practice-results-from-the-nationwide-danish-danbio-registry/