Osteopontin regulates anabolic effect in human menopausal osteoporosis with intermittent parathyroid hormone treatment

Abstract

In this pilot study, we demonstrated that women with osteopontin (OPN) over-expression show less resistance to postmenopausal osteoporosis than women with normal OPN levels. We hypothesized that the levels of plasma OPN could be used as a treatment indicator for intermittent parathyroid hormone (PTH)-treated menopausal osteoporosis. We demonstrated that plasma OPN levels could be used as a biomarker for early treatment response.

Introduction: Animal studies indicate that OPN-deficient mice are resistant to ovariectomy induced osteoporosis. Our pilot study also demonstrated women with OPN over expression may show less resistance to postmenopausal osteoporosis. The role of plasma OPN in PTH1-34-treated osteoporosis remains unclear.

Methods: From September 2005 to September 2006, 31 menopausal women over 45 years of age with severe osteoporosis were enrolled in our study. Subjects were treated with PTH1-34 subcutaneously at a dose of 20 μg/day. Plasma OPN levels and BMD of the lumbar spine and hip were measured using ELISA and dual-energy X-ray absorptiometry at baseline, 3, 6, and 9 months. Response to the treatment was assessed by the sequential change in bone mineral density and OPN expression using a general linear mixed model.

Results: The plasma OPN decreased sequentially and significantly throughout the 9-month treatment course from 20.75 ± 5.36 to 11.2 ± 4.37 ng/ml (p < 0.001). The sequential improvement in the T-score and Z-score was significant in the lumbar spine but not in the hip area. In the lumbar spine, when the plasma OPN decreased by 1 ng/ml the T-score increased by 0.0406 and the Z-score increased by 0.0572 of lumbar spine.

Conclusion: OPN levels are related to the anabolic effect of PTH in human postmenopausal osteoporosis. Plasma OPN levels could be used as a biomarker for early treatment response.