Effects of Intermittent Parathyroid Hormone 1–34 Administration on Circulating Mesenchymal Stem Cells in Postmenopausal Osteoporotic Women

Abstract

BACKGROUND Intermittent parathyroid hormone (PTH) 1-34 administration stimulates osteogenesis and increases bone marrow mesenchymal stem cell (MSC) density; however, its effect on the circulating MSCs is unknown. This study aimed to examine the effect of intermittent PTH 1-34 administration on circulating MSCs in the peripheral blood of postmenopausal osteoporotic women. MATERIAL AND METHODS Fifty-four postmenopausal osteoporotic women at high risk of fracture were enrolled and administered either teriparatide (PTH 1-34) or alendronate for 12 months. Whole blood samples were obtained at baseline, 1, 3, 6, and 12 months after initiation of treatment. Flow cytometry analyses were performed to identify circulating MSCs (CD73+, CD90+, CD105+, CD34-, and CD45-). Serum markers of bone formation, bone resorption, as well as bone mineral density (BMD) were serially measured. Circulating MSCs were isolated from peripheral blood of teriparatide treated women and cultured in osteogenic medium to examine their osteogenic differentiation potential. RESULTS Teriparatide treatment increased circulating MSCs to 141±96% (P<0.001) by month 1, persisting until month 12; this increase was positively associated with increases in bone formation and bone resorption biomarkers (at month 6) and spine BMD (at month 12). Furthermore, intermittent PTH 1-34 administration promoted in vitro osteogenic differentiation of circulating MSCs, evident from increased alkaline phosphatase (ALP) activity, ALP-expressing cell density, calcium deposition, and Runx-2, OSX, COL 1a1, and osteocalcin mRNA upregulation. CONCLUSIONS Intermittent PTH 1-34 administration increased circulating MSC density in women with postmenopausal osteoporosis and enhanced in vitro osteogenic differentiation potential of these cells.