Association between circulating osteoblast progenitor cells and aortic calcifications in women with postmenopausal osteoporosis.

BACKGROUND AND AIMS: Ectopic artery calcification has been documented in women with postmenopausal osteoporosis, in whom an imbalance in the number of circulating osteoprogenitor cells (OPCs) has been identified. Circulating OPCs form calcified nodules in vitro; however, it remains unknown whether an association exists between the number of circulating OPCs and aortic calcifications. We investigated the relationship between OPCs and aortic calcifications in women with postmenopausal osteoporosis. METHODS AND RESULTS: The number of circulating OPCs was quantified by FACS analysis in 50 osteoporotic postmenopausal women. OPCs were defined as CD15-/alkaline-phosphatase(AP)+ cells coexpressing or not CD34. Participants underwent measurement of markers of bone metabolism, bone mineral density and abdominal aortic calcium (AAC) by 64-slice computed tomography. Patients with AAC were older, had lower 25(OH)vitamin D levels and higher circulating CD15-/AP+/CD34- cells than those without AAC. Significant correlates of AAC included age (rho = 0.38 p = 0.006), calcium (rho = 0.35 p = 0.01), 25(OH)vitamin D (rho = -0.31, p = 0.03) and the number of CD15-/AP+/CD34- cells (rho = 0.55 p < 0.001). In regression analyses, the log-transformed number of CD15-/AP+/CD34- cells was associated with the presence (OR = 6.45, 95% CI 1.03-40.1, p = 0.04) and severity (ß = 0.43, p < 0.001) of AAC, independent of age, 25(OH)vitamin D, calcium and other potential confounders. Patients with low 25(OH)vitamin D and high CD15-/AP+/CD34- cells had higher median AAC than other patients (1927/µL, 862-2714/µL vs 147/µL, 0-1665/µL, p = 0.003). CONCLUSION: In women with postmenopausal osteoporosis, the number of circulating CD15-/AP+/CD34- cells is significantly associated with increased aortic calcifications, that appear to be correlated also with reduced 25(OH)vitamin D levels.

Circulating immature osteoprogenitor cells and arterial stiffening in postmenopausal osteoporosis.

BACKGROUND AND AIMS: An increased number of circulating osteoprogenitor cells (OPCs) expressing bone-related proteins and the stem cell marker CD34 have been identified in women with postmenopausal osteoporosis, who also have stiffer arteries than nonosteoporotic subjects. We investigated whether an increased number of circulating OPCs underlies the association of osteoporosis with arterial stiffness. METHODS AND RESULTS: The number of circulating OPCs was quantified by FACS analysis in 120 postmenopausal women with or without osteoporosis. OPCs were defined as CD34+/alkaline phosphatase(AP)+ or CD34+/osteocalcin(OCN)+ cells. Participants underwent cardiovascular risk factor assessment, measurement of bone mineral density (BMD), and aortic pulse wave velocity (aPWV) as a measure of arterial stiffness. Osteoporotic women had higher aPWV (9.8 ± 2.8 vs 8.5 ± 1.9 m/s, p = 0.005) and levels of CD34+/AP+ and CD34+/OCN+ cells than nonosteoporotic controls [1045 n/mL (487-2300) vs 510 n/mL (202-940), p < 0.001; 2415 n/mL (1225-8090) vs 1395 n/mL (207-2220), p < 0.001]. aPWV was associated with log-CD34+/AP+ (r = 0.27, p = 0.003), log-CD34+/OCN+ cells (r = 0.38, p < 0.001). In stepwise regression analysis CD34+/OCN+ cells, age, systolic blood pressure and heart rate were significant predictors of aPWV (Model R = 0.62, p < 0.001), independent of cardiovascular risk factors, parathyroid hormone levels and osteoporotic status. CONCLUSION: In women with postmenopausal osteoporosis an increased availability of circulating osteoprogenitor cells has a detrimental influence on arterial compliance, which may in part explain the association between osteoporosis and arterial stiffening.

Association between circulating osteoprogenitor cell numbers and bone mineral density in postmenopausal osteoporosis.

UNLABELLED: The role of circulating osteoprogenitor cells in postmenopausal osteoporosis is unknown. We found that alkaline-phosphatase-positive (AP+) cells are the lacking cells in osteoporosis, whose reduction is related to bone loss. Conversely, the increased number of alkaline phosphatase/CD34-positive cells may reflect the reactive bone marrow contribution to bone formation. INTRODUCTION: Circulating osteoprogenitor cells mineralize in vitro and in vivo. Loss of osteogenic cells may account for bone loss in osteoporosis. We studied whether there is an association between the number of circulating osteoprogenitor cells and bone mineral density (BMD) in postmenopausal women with and without osteoporosis. METHODS: The number of circulating AP+, osteocalcin-positive (OCN+), AP+/CD34+, and OCN+/CD34+ cells was quantified in 54 postmenopausal osteoporotic women and 36 age-matched nonosteoporotic controls. RESULTS: The number of AP+ cells was lower in osteoporotic women than in controls (127 +/- 16 vs 234 +/- 23 per microliter; p < 0.001); higher levels of AP+/CD34+, OCN+, and OCN+/CD34+ cells were found in osteoporotic than controls (p < 0.01 for all). The number of AP+ cells was correlated with lumbar BMD (rho = 0.29; p = 0.008) and proximal femur BMD (rho = 0.31; p = 0.005) whereas inverse correlations were found between AP+/CD34+ cells, OCN+, OCN+/CD34+, and BMD. Reduced AP+ cells and increased AP+/CD34 +, OCN+, and OCN+/CD34+ cells were predictors of low BMD, independent of traditional risk factors for osteoporosis. CONCLUSION: In postmenopausal osteoporotic women, a reduced number of circulating AP+ cells and increased levels of AP+/CD34+, OCN+, and OCN+/CD34+ cells are associated with reduced bone mineral density, the interpretation of such a cellular imbalance needing exploration.