title: Association between thyroid hormone levels, the number of circulating osteoprogenitor cells, and bone mineral density in euthyroid postmenopausal women.
abstract: In postmenopausal women, an association between reduced bone mineral density (BMD) and increased number of circulating osteoprogenitor cells (COPs) has been found. Although an increased thyroid function is associated with BMD, thyroid hormones stimulate osteoblast function in vitro. We investigated whether thyroid hormones within the reference range were correlated with the number of COPs and stimulate mineralization in vitro. The number of COPs, defined as CD34+/alkaline phosphatase (AP)+ or CD34+/osteocalcin (OCN)+ cells, was quantified by fluorescence-activated cell sorting (FACS) analysis in 150 euthyroid postmenopausal women. Participants underwent measurement of serum free thyroxine (FT4), thyroid-stimulating hormone levels, and femur BMD. CD34+ cells were isolated from healthy volunteers irrespective of AP or OCN expression, and the effect of triiodothyronine (0.5-10 pmol/L)) on their ability to form mineralized nodules in vitro was studied. The number of COPs was highest among women with high-normal FT4 levels (>1.09 ng/dL). The FT4 levels were correlated positively with circulating log-CD34+/AP+ (r = 0.32, P < .001) and log-CD34/OCN+ cells (r = 0.36, P < .001) and inversely with total femur BMD (r = -0.17, P = .036) but not with femoral neck BMD. In a multivariate analysis, the FT4 levels were positively correlated with the number of COPs, independent of age and BMD. The ability of CD34+ cells to form mineralized nodules increased after exposure from low up to high-normal triiodothyronine concentrations (P for trend = .003). Among euthyroid postmenopausal women, high-normal FT4 levels are correlated with an increased number of circulating immature osteoprogenitor cells and a very mild BMD reduction. Exposure of CD34+ cells to physiological triiodothyronine concentrations stimulates mineralization in vitro.
authors.affiliation: Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. mpirro@unipg.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Pirro
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Manfredelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Scarponi
authors.forename: Graziana
authors.initials: G
authors.lastname: Lupattelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Bagaglia
authors.forename: Francesco
authors.initials: F
authors.lastname: Melis
authors.forename: Elmo
authors.initials: E
authors.lastname: Mannarino
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D018952:Antigens, CD34 / Q000097:blood / Q000378:metabolism; D015519:Bone Density; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D017698:Postmenopause / Q000097:blood / Q000378:metabolism*; D012044:Regression Analysis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D013963:Thyroid Hormones; D015675:Osteocalcin; D000469:Alkaline Phosphatase