Background/Purpose:

Systemic lupus erythematosus (SLE) has been associated with an increased risk of low bone mineral density and fractures. However, data on absolute fracture risk and risk factors associated with clinical fractures are very scarce. The purpose of the present study was to estimate incidence rates of clinical fractures in patients with SLE and relative risks compared with matched controls, and to evaluate risk factors associated with fractures in SLE.

Methods:

We conducted a population-based cohort study using the Clinical Practice Research Datalink (from 1987 to 2012). Each SLE patient (n=4343) was matched with up to 6 controls (n=21780) by age and sex. Fracture type was stratified according to WHO definitions into osteoporotic fracture (clinical spine, hip, forearm, or humerus) and non-osteoporotic fracture. Cox proportional hazards models were used to calculate relative rates (RR) of fracture, and time interaction terms to evaluate fracture timing patterns. Incidence rates of fractures in SLE patients, stratified by age, gender, type of fracture, disease duration, and therapy variables, were compared with fracture rates in controls.

Results:

Mean age was 46.7 years. Follow-up duration was 6.4 years in SLE patients and 6.6 years in matched controls. Overall, SLE patients had an increased risk of any fracture compared to controls, after adjustment for confounders (adj RR 1.22; 95% confidence interval (CI) 1.05-1.42), and the risk further increased with a longer disease duration. Glucocorticoid (GC) use in the previous six months raised the risk of any fracture (adj RR 1.27; 95% CI 1.02-1.58), but was not further increased with higher cumulative GC exposure. A similar pattern was found for osteoporotic fracture, but did not reach statistical significance (adj RR 1.23; 95% CI 0.91-1.67). Use of antimalarials was not associated with an altered fracture risk. Cerebrovascular events, seizures, and (as expected) previous osteoporotic fractures were identified as significant predictors for any and osteoporotic fractures (Table 1).

Conclusion:

SLE patients in the United Kingdom have an increased risk of clinical fractures compared to age- and sex-matched controls. GC use in the previous six months and longer disease duration are important factors associated with the increased fracture risk in SLE. In addition, special attention should be paid to lupus patients with neuropsychiatric organ damage or a history of osteoporotic fractures since these subgroups of patients are at high risk of the occurrence of (subsequent) fractures.

Table 1. Risk of fracture within SLE patients (n=4343), stratified according to organ damage. (reference = no risk factor)

	Any fracture		Osteoporotic fracture
	Events	Adj RR (95% CI)*	Events	Adj RR (95% CI)*
Cognitive impairment	5	1.67 (0.68-4.08)	4	2.25 (0.82-6.16)
Seizures	34	2.01 (1.41-2.86)	22	2.81 (1.80-4.40)
Cerebrovascular event	55	1.49 (1.12-2.00)	35	1.77 (1.22-2.57)
Renal disease	54	1.30 (0.96-1.75)	32	1.35 (0.91-2.00)
Previous osteoporotic fracture	172	4.26 (3.49-5.18)	95	3.85 (2.92-5.07)
Diabetes	21	1.39 (0.89-2.17)	11	1.33 (0.72-2.45)
Malignancy	50	1.23 (0.91-1.68)	28	1.22 (0.81-1.84)

 *Adjusted for: previous fracture, use of glucocorticoids, antimalarials, calcium/vitamin D supplements, benzodiazepines, and proton pump inhibitors in the previous 6 months.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-of-and-risk-factors-for-clinical-fractures-in-patients-with-systemic-lupus-erythematosus-and-matched-controls-a-population-based-study-in-the-united-kingdom/