Low-income Americans with systemic lupus erythematosus (SLE) had double the risk of fractures compared with matched controls without SLE, analysis of Medicaid data found.
The hazard ratio for any fracture among patients with SLE was 2.09 (95% CI 1.85-2.37), according to Sara K. Tedeschi, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
And risks were even higher among SLE patients with nephritis (HR 3.06, 95% CI 2.24-4.17), the researchers reported online in Arthritis & Rheumatology.
Impaired bone health is common among patients with SLE, for reasons relating to both the disease and its treatment. “High circulating levels of inflammatory cytokines stimulate bone resorption, and greater SLE activity has been associated with low bone mineral density,” the researchers explained.
In addition, treatment with glucocorticoids — both daily doses and cumulative doses — can have a major impact on bone mineral density. When kidney involvement is present, patients can develop vitamin D deficiencies and hyperparathyroidism, further compromising bone health.
Yet little is known about the risk for fracture in these patients, and particularly among minorities and less affluent patients who typically have more disease complications.
To explore these concerns, Tedeschi and colleagues undertook a cohort study of SLE patients enrolled in Medicaid during the years 2007-2010, analyzing fracture rates for pelvis, wrist, hip, and humerus. Vertebral fractures were not included, because these can be asymptomatic and rates can be difficult to establish in claims-based analyses, the team explained.
Covariates included demographics, comorbidities, and medications such as hydroxychloroquine, azathioprine, mycophenolate mofetil (CellCept), cyclophosphamide, and rituximab (Rituxan). Prednisone use was characterized as low-dose (less than 7.5 mg/day) or high-dose (7.5 mg/day or more).
The analysis included 47,709 patients with SLE and 190,836 individuals enrolled in Medicaid without SLE. A total of 19.8% of the SLE patients had nephritis.
More than 90% were women, and mean age was 41. Median household income was slightly higher than $45,000.
More patients in the SLE group were African-American (43% vs 22%). Almost one-third were on low doses of prednisone and 13% were taking high doses. Hydroxychloroquine, which is considered a mainstay of lupus treatment, was being used only by 36%. A total of 5.8% of SLE patients had prescriptions for bisphosphonates, as did 0.7% of non-SLE controls.
The incidence ratios for any fracture were 4.32/1,000 person-years among SLE patients, 4.60/1,000 for SLE patients with nephritis, and 2.40/1,000 among non-SLE controls. The most common type of fracture in the SLE group overall was pelvic, with an incidence ratio of 1.72/1,000 person-years. The risks of pelvic fracture were even higher in the nephritis subgroup, at 2.23/1,000. In the control group, wrist fractures were the most frequent (1.04/1,000).
After adjustment for baseline prednisone use, fracture risks relative to non-SLE individuals were as follows:
- Overall: HR 1.78, 95% CI 1.55-2.05
- Hip: HR 3.22, 95% CI 2.33-4.46
- Pelvis: HR 2.63, 95% CI 2.13-3.24
- Humerus: HR 1.82, 95% CI 1.34-2.47
- Wrist: HR 1.57, 95% CI 1.27-1.94
The subgroup of SLE patients with nephritis not only had an increased risk of any fracture compared with non-SLE controls, but also compared with SLE patients without nephritis (HR 1.58, 95% CI 1.20-2.07).
Among patients under age 50, the hazard ratio for fracture was 2.28 (95% CI 1.90-2.74) compared with controls, and for those over 50, the hazard ratio was 1.92 (95% CI 1.61-2.28), with slight attenuation after adjustment for comorbidities and prednisone use.
The American College of Rheumatology has recommended use of bisphosphonates for patients on long-term prednisone who are at moderate or high risk of fracture. “However, renal disease often contraindicates preventive treatment with bisphosphonates,” the investigators wrote.
Glucocorticoid use could account for only some of the increased risk, and suboptimal practice patterns also may have contributed, as evidenced by the low rate of hydroxychloroquine use, Tedeschi and co-authors noted.
“This work underscores the importance of identifying high-risk SLE and lupus nephritis patients for fracture prevention,” they concluded.
Limitations of the study, the researchers said, included a lack of information on body mass index, physical activity, and duration of disease.
The study was supported by the Lupus Foundation of America and the National Institutes of Health.
The authors reported having no conflicts of interest.