Changes in circulating osteoblast lineage cells following PTH (1–34) therapy and correlation with changes in trabecular bone mass

Document Type

Conference Paper

Department

Paediatrics and Child Health

Abstract

Using flow-cytometry, we previously demonstrated a five-fold increase in circulating osteoblast progenitor cells in pubertal boys compared to adult males (NEJM 352:1959–1966). We recently further classified these osteocalcin (OCN) positive cells into two distinct populations: small, relatively agranular cells that co-stained for the stem cell marker, CD34 (OCNsmall, which may represent a less differentiated cell population), and larger, more granular cells that were CD34 negative (OCNgran, which may represent a more differentiated cell population) (Bone 40:1370–1377). To evaluate the effects of PTH therapy on these cells, we studied 8 women at baseline, 3 months and 12 months after starting 20 meg/day rh 1–34 PTH (Forteo). All 8 subjects completed the baseline and 3 month visit, and 7 of the 8 completed the 12 month visit. Panel A in the figure shows the changes in the OCNsmalland OCNgran cells. At 3 months, there was no significant change in the OCNsmall cells, but a trend for an increase (of 26%, P = 0.14) in the OCNgran cells. However, at 12 months, this pattern was reversed, with the OCNsmall cells showing a marked increase (of 64%, P = 0.016), and the OCNgran showing a decrease back to baseline levels. Interestingly, the percent change in OCNgran cells between 0 and 12 months was highly positively correlated (R = 0.82, P = 0.02) with changes in bone volume/tissue volume (BV/TV) as assessed by high resolution 3D-pQCT (Xtreme CT, Scanco) in these patients (Panel B). The mean (± SEM) increase in BV/TV in the subjects who had an increase in the OCNgran cells between baseline and 12 months was 10.8 ± 3.25% as compared to 1.7 ± 0.6% in the subjects who had a decrease in these cells (P = 0.066). To the extent that the OCNsmall cells and OCNsmall cells represent less as compared to more differentiated osteoprogenitor populations, respectively, our findings suggest that PTH initially expands the population of more mature osteoprogenitor cells, whereas over a longer period of time this effect wanes, and more immature cells are recruited along the osteoblast pathway. Sustained increases in the more differentiated cells appear to be predictive of larger gains in trabecular bone volume, although further studies characterizing the relative osteoblastic differentiation of the OCNsmall vs. OCNgran are needed to test this hypothesis.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of Bone and Mineral Research

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