Correlation of Serum CCL3/MIP-1α Levels with Disease Severity in Postmenopausal Osteoporotic Females

Background: The pro-inflammatory protein chemokine cytokine ligand 3 is well established as a vital regulator of bone resorption and osteoclast stimulation.

Aims: To investigate if serum cytokine ligand 3 levels correlated with disease severity in postmenopausal osteoporotic women.

Study design: Cross-sectional study.

Methods: Eighty-two postmenopausal osteoporotic women, 76 postmenopausal non-osteoporotic women, and 80 healthy women of childbearing age were recruited. The total hip, femoral neck, and L1-L4 spine bone mineral density were assessed by dual-energy X-ray absorptiometry. Serum cytokine ligand 3 concentrations were examined using a commercial enzyme-linked immunosorbent assay kit. Serum inflammatory cytokine interleukin-6, tumor necrosis factor-alpha, and the bone metabolic markers, carboxy-terminal crosslinked and tartrate-resistant acid phosphatase 5b were also examined. Scores on both the visual analogue scale and the Oswestry Disability Index were utilized to assess clinical severity.

Results: Patients in the postmenopausal osteoporotic group had significantly increased serum cytokine ligand 3 levels compared with those in both the postmenopausal non-osteoporotic group (40.9±15.1 pg/mL vs 24.2±8.7 pg/mL, p<0.001) and control group (40.9±15.1 pg/mL vs 23.9±9.1 pg/mL, p<0.001). Serum cytokine ligand 3 levels negatively correlated with bone mineral density at the total hip (r=-0.345, p=0.002), femoral neck (r=-0.329, p=0.003), and L1-L4 lumbar spine (r=-0.354, p=0.001) and positively correlated with visual analogue scale scores (r=0.413, p<0.001) and the Oswestry Disability Index (r=0.360, p<0.001). Moreover, serum cytokine ligand 3 levels were correlated with increased tumor necrosis factor-alpha (r=0.305, p=0.005), interleukin-6 (r=0.288, p=0.008), terminal crosslinked and tartrate-resistant acid phosphatase 5b (r=0.371, p<0.001), and carboxy-terminal crosslinked (r=0.317, p=0.004) levels. All correlations were still significant after adjusting for both body mass index and age.

Conclusion: Chemokine cytokine ligand 3 may be a useful biomarker that can be used to predict disease severity of postmenopausal osteoporosis. Therapies targeting cytokine ligand 3 and its related signaling pathways to inhibit and delay the osteoclastogenesis process deserve further investigation.