Relationship between osteoporosis and adipose tissue leptin and osteoprotegerin in patients with chronic obstructive pulmonary disease

IntroductionThe role of fat–bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. Our aim was to investigate expressions of leptin and osteoprotegerin (OPG) in the adipose tissue, and their relationships to osteoporosis in patients with COPD.MethodsIn 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by Dual Energy X-Ray Absorptiometry. Serum leptin was determined by the enzyme-linked immunosorbent assay, and bone turnover markers osteocalcin and β-crosslaps by the electrochemiluminiscence immunoassays. Subcutaneous adipose tissue samples were analyzed using real-time PCR.ResultsTwenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2 ± 7.3 years). Compared to patients without osteoporosis, those with the disease had significantly lower serum levels and adipose tissue expressions of leptin, in association with increased serum β-crosslaps (p = 0.028, p = 0.034, p = 0.022, respectively). Log adipose tissue leptin was inversely related to serum β-crosslaps (p = 0.015), and directly to serum leptin (p < 0.001) and to the total, femoral, and lumbar BMD and T-score (p < 0.02 for all relationships). Adipose tissue OPG expression was related to all variables of bone density except for lumbar BMD and T-score (p < 0.05 for all relationships). Log adipose tissue leptin and OPG expressions predicted femoral T-score independently of age, gender and pulmonary function (p < 0.001, adjusted R2 = 0.383; p = 0.008, adjusted R2 = 0.301, respectively). Introducing body mass (or fat mass) index into these models eliminated independent predictive value of leptin and OPG expressions.ConclusionOur results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD.

Research highlights
► Osteoporosis is related to reduced leptin expression in adipose tissue (AT) in COPD.
► AT leptin expression correlates with bone mineral density (BMD) and β-crosslaps.
► AT osteoprotegerin (OPG) expression correlates with BDM and β-crosslaps.
► AT leptin and OPG predicted BMD independently of age, gender and lung function.
► Adjustments for adiposity eliminated independent predictive value of leptin and OPG.