Hypoalbuminemia and Osteoporosis: Reappraisal of a Controversy.

Context: Human studies have reported conflicting results on the association of hypoalbuminemia with osteoporosis. Objective: The aim of the study is to test the independent association between hypoalbuminemia and osteoporosis. Design: This is a cross-sectional observation. Setting and Participants: Patients are the outpatient consecutive individuals with available clinical, laboratory, and densitometry data from 2001 to 2013 in our tertiary care academic medical center. Exposure: Exposure is hypoalbuminemia defined as serum albumin less than 3.5 g/dL. Main Outcome Measure: Osteoporosis is defined as bone mineral density of 2.5 SD or less below the mean peak bone mass of young, healthy adults. Results: Overall, 21 121 patients were included. Mean of age was 61 years (SD 14). There were 4244 males (20.1%) and 1614 patients of African-American ethnicity (7.6%). There was a graded decrease in rate of osteoporosis from 28.0% (n = 33) at albumin of 3 g/dL or less to 9.3% (n = 1548) at albumin greater than 4 g/dL (P < .001) at the femoral neck and from 20.3% (n = 24) to 6.1% (n = 1011) at the total hip (P < .001). In a fully adjusted model, the odds of osteoporosis at albumin of 3 g/dL or less was 3.31-fold (95% confidence interval [CI] 2.08-5.28, P < .001) at the femoral neck, 2.98-fold (95% CI 1.76-5.01, P < .001) at the total hip, and 2.18-fold (95% CI 1.43-3.31, P < .001) at the lumbar spine as compared with albumin greater than 4 mg/dL. A similar independent association was identified with a longer-observed duration of hypoalbuminemia. Conclusion: In a large population, we report an independent association of osteoporosis with lower levels of serum albumin and a longer-observed duration of hypoalbuminemia.