Abstract
Summary
This study shows that teriparatide promotes the circulating osteoblast (OB) precursor degree of maturation in patients affected by postmenopausal osteoporosis.
Introduction
Anabolic treatment with teriparatide has proven effective for the therapy of postmenopausal osteoporosis and significantly reduces the risk of non-vertebral fragility fractures. The aim of this study was to investigate the effect of teriparatide on circulating OB precursors.
Methods
We evaluated by flow cytometry and real-time PCR the expression of OBs typical markers in peripheral blood mononuclear cells during treatment with teriparatide plus calcium and vitamin D, raloxifene plus calcium and vitamin D or calcium and vitamin D alone at various time points. Serum bone alkaline phosphatase and osteocalcin (OC) were measured as markers of bone turnover.
Results
Our results show that circulating OB precursors are more numerous and more immature in patients affected by fragility fractures than in osteoporotic patients without fractures. We also show that teriparatide treatment increases the expression of alkaline phosphatase and of OC in OB precursors; thus, it increases their degree of maturation.
Conclusions
We suggest that teriparatide acts as anabolic agents also by promoting the maturation of OB precursors.
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Acknowledgments
This work was supported by an unrestricted grant from Ely Lilly and the Fondazione Internazionale Ricerche Medicina Sperimentale (FIRMS) Compagnia San Paolo. SP was supported by a fellowship from the Italian Association for Cancer Research (AIRC); FS was supported by a fellowship of the Regione Piemonte. Teriparatide and Raloxifene were kindly provided by Ely Lilly; calcium and vitamin D supplements were kindly provided by Italfarmaco SpA.
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supplemental Fig. 1
Flow cytometry analyses of OB precursors. a Dot plot represents PBMCs, monocytes are indicated (R1). b Dot plot represents CD 15 positive cells (R2) analyzed on the whole PBMCs population. c Dot plot represents monocytes positive for AP and OC, CD15-positive cells (R2) were excluded by the analyses. d Histogram represents the mean fluorescence intensity (MFI) of OC+ cells (gated on monocytes after exclusion of CD 15+ cells). Broken line is the isotype control; unbroken line is the stained sample. (PPT 271 kb)
supplemental Table 1
Gene primer sequences. F forward, R reverse. All the genes were quantified by considering signals under 33 Ct. (DOC 26 kb)
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D’Amelio, P., Tamone, C., Sassi, F. et al. Teriparatide increases the maturation of circulating osteoblast precursors. Osteoporos Int 23, 1245–1253 (2012). https://doi.org/10.1007/s00198-011-1666-2
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DOI: https://doi.org/10.1007/s00198-011-1666-2