Newly Diagnosed Cases of SLE at 62% Increased Risk for Hip Fracture
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Patients newly diagnosed with systemic lupus erythematosus demonstrate a 62% increased risk for hip fractures compared with those without lupus, according to data published in Arthritis Care & Research.
“Previous studies have shown that patients with SLE have an increased risk of osteoporosis and fractures,” Lingyi Li, MSc, of Arthritis Research Canada, and colleagues wrote. “Hip fractures represent the most devastating complication of osteoporosis with up to 30% one-year mortality and 60% five-year mortality. However, studies on whether SLE is an independent risk factor for hip fractures (regardless of glucocorticoid use) are scarce and inconclusive, especially population-based studies.”
To evaluate the independent risk for hip fractures among patients newly diagnosed with SLE, compared with the general population, Li and colleagues studied a cohort from Population Data BC, a database of all provincially funded health care service information in British Columbia, Canada, from Jan. 1, 1990, to March 31, 2015. The database also includes PharmaNet, which captures all prescribed medications in outpatient settings for all provincial residents since 1996.
Focusing on a time between Jan. 1, 1997, and March 31, 2015, the researchers assembled a cohort of 5,047 patients with incident SLE who received health care during that time. A total of 25,235 individuals without SLE were randomly selected from the general population and matched 5:1 to those with SLE, based on age, sex and index year. The primary outcome was first hip fracture following study entry.
The researchers calculated cumulative incidence after accounting for competing risks for death, and used marginal structural Cox models to estimate the effect of SLE on hip fractures, adjusting for covariates such as glucocorticoid use and the number of outpatient, inpatient and rheumatology visits.
According to the researchers, there were 73 hip fractures among patients with SLE during 78,915 person-years, compared with 272 hip fractures among those without SLE during 395,427 person-years. This resulted in a crude incidence rate ratio of 1.34 (95% CI, 1.02-1.75). After adjusting for baseline covariates, the HR was 1.86 (95% CI, 1.37-2.52), while further adjustment for time-dependent covariates moved the figure to a still-significant 1.62 (95% CI, 1.06-2.48).
“This population-based study demonstrates that patients with SLE have an approximately 60% increased risk of sustaining a hip fracture compared to the general population,” Li and colleagues wrote. “This result expands on the findings of previous studies and has important implications for the prevention, screening and treatment of osteoporosis that may lead to hip fractures. Further studies should clarify the impact of inflammation, glucocorticoid dosage and duration of use on the risk of hip fractures among SLE patients.” – by Jason Laday
Disclosure: The researchers report relevant financial disclosures.
Perspective
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David A. McLain, MD, FACP, FACR
When we see patients in the rheumatology clinic and we think about osteoporosis, we think of the elderly patients, those on long-term corticosteroids, and those with rheumatoid arthritis. We think about osteoporosis in lupus patients that have been on corticosteroids, particularly at medium- to high-doses for months to years.
In this study, the researchers examined a very large database, with more than 5,000 lupus patients and 25,000 patients without lupus to serve as controls. Their analysis revealed an increased risk of hip fracture in newly diagnosed SLE, even when corticosteroids were not a factor.
When we see our SLE patients, we need to be cognizant that, as with RA, SLE is an independent risk factor for hip fractures. The reason for bone loss, even in the absence of glucocorticoids, is likely to be multifactorial. In SLE, there are increased levels of oxidized LDL which can activate T-cells, which in turn increases production of receptor activator of nuclear factor kappa-B ligand (RANKL) and TNF. Both of these increase the maturation and activity of osteoclasts; oxidized LDL also decreases maturation of osteoblasts.
Evidence for the increased activity of osteoclasts and decreased activity of osteoblasts has been reported in premenopausal women with recently diagnosed, untreated SLE; findings consistent with the increased activity of osteoclasts (increased excretion of crosslinks in the urine) and decreased osteoblastic activity (decreased serum levels of osteocalcin) have also been published. The effects of glucocorticoids on bone metabolism have been well documented, but include a decrease in vitamin D levels, stimulation of bone resorption and reduction in bone formation.
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