Mortality and cardiovascular burden of systemic lupus erythematosus in a US population-based cohort.

OBJECTIVE: To examine the mortality and cardiovascular disease (CVD) burden among a population-based cohort of patients with systemic lupus erythematosus (SLE) with previously described late mean onset and low rates of organ-threatening disease. METHODS: This retrospective population-based cohort study investigated incident cases of SLE diagnosed from 1991-2008 and followed through March 2009 to examine rates of death and CVD events: myocardial infarction, stroke, or congestive heart failure hospitalization. Cases were identified using the 1997 update of the 1982 American College of Rheumatology SLE criteria. Searches included electronic records, chart audits, and state death matches, with physician review. Age-matched and sex-matched population comparisons facilitated relative event rate calculations. RESULTS: Seventy incident SLE cases had late mean onset (52 years), with an incidence of 5 cases per 100,000/year. Matched comparisons showed similar baseline rates of hypertension, hyperlipidemia, and diabetes. However, patients with SLE experienced more CVD in the 2 years preceding SLE diagnosis (OR 3.8, 95% CI 1.8, 8.0). The estimated 10-year mortality rates were 26% for SLE subjects versus 19% for comparisons, hazard ratio (HR) 2.1, p<0.01. Adjusted for prior CVD, SLE cases still demonstrated increased hazards of mortality (HR 1.9, p=0.01) and CVD event or death (HR 1.8, p=0.01). CONCLUSION: This incident SLE cohort demonstrated nearly doubled mortality and CVD event hazards compared to age-matched and sex-matched comparisons, even after accounting for higher CVD events in the 2 years preceding SLE diagnosis. This raises research questions regarding delayed SLE diagnosis versus accelerated CVD prior to SLE, particularly in older-onset SLE.

Severely suppressed bone turnover and atypical skeletal fragility.

CONTEXT: Since their introduction into clinical medicine, bisphosphonates have revolutionized clinical osteoporosis care. Ironically, in rare circumstances, long-term, combined anti-remodeling therapy may be associated with skeletal harm. EVIDENCE ACQUISITION: We report atypical skeletal fragility in three subjects after long-term, combined anti-remodeling therapy. EVIDENCE SYNTHESIS: Three subjects experienced spontaneous or minimal-trauma chalk-stick type metadiaphyseal femoral fractures while on long-term bisphosphonate therapy. The fracture location, type, bilaterality, prodromal pain, and delayed healing were atypical for uncomplicated postmenopausal osteoporosis. All three subjects had concomitant circumstances (endogenous estrogen) or medications (glucocorticoids, hormone replacement therapy, and raloxifene) that likely suppressed bone remodeling beyond the effect of the bisphosphonate alone. Biochemical markers of bone turnover were very low or in the low premenopausal range. Double tetracycline-labeled bone biopsy showed very low activation frequency in one subject and limited single tetracycline label in a second consistent with severely suppressed bone turnover (SSBT). These three cases resemble previous descriptions of SSBT. CONCLUSION: Atypical skeletal fragility may signify SSBT in the setting of long-term, combined anti-remodeling therapy. We speculate that osteoclast tolerance for pharmacological suppression may vary among individual patients and that in some cases combined anti-remodeling therapy may result in skeletal harm.