Parathyroid hormone stimulates circulating osteogenic cells in hypoparathyroidism.
BACKGROUND
The osteoanabolic properties of PTH may be due to increases in the number and maturity of circulating osteogenic cells. Hypoparathyroidism is a useful clinical model because this hypothesis can be tested by administering PTH.


OBJECTIVE
The objective of the study was to characterize circulating osteogenic cells in hypoparathyroid subjects during 12 months of PTH (1-84) administration.


METHODS
Osteogenic cells were characterized using flow cytometry and antibodies against osteocalcin, an osteoblast-specific protein product, and stem cell markers CD34 and CD146. Changes in bone formation from biochemical markers and quadruple-labeled transiliac crest bone biopsies (0 and 3 month time points) were correlated with measurements of circulating osteogenic cells.


METHODS
The study was conducted at a clinical research center.


METHODS
Nineteen control and 19 hypoparathyroid patients were included in the study.


METHODS
Intervention included the administration of PTH (1-84).


RESULTS
Osteocalcin-positive cells were lower in hypoparathyroid subjects than controls (0.7 ± 0.1 vs. 2.0 ± 0.1%; P < 0.0001), with greater coexpression of the early cell markers CD34 and CD146 among the osteocalcin-positive cells in the hypoparathyroid subjects (11.0 ± 1.0 vs. 5.6 ± 0.7%; P < 0.001). With PTH (1-84) administration, the number of osteogenic cells increased 3-fold (P < 0.0001), whereas the coexpression of the early cell markers CD34 and CD146 decreased. Increases in osteogenic cells correlated with circulating and histomorphometric indices of osteoblast function: N-terminal propeptide of type I procollagen (R(2) = 0.4, P ≤ 0.001), bone-specific alkaline phosphatase (R(2) = 0.3, P < 0.001), osteocalcin (R(2) = 0.4, P < 0.001), mineralized perimeter (R(2) = 0.5, P < 0.001), mineral apposition rate (R(2) = 0.4, P = 0.003), and bone formation rate (R(2) = 0.5, P < 0.001).


CONCLUSIONS
It is likely that PTH stimulates bone formation by stimulating osteoblast development and maturation. Correlations between circulating osteogenic cells and histomorphometric indices of bone formation establish that osteoblast activity is being identified by this methodology.
Rubin
M R
MR
Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. mrr6@columbia.edu
Manavalan
J S
JS
Dempster
D W
DW
Shah
J
J
Cremers
S
S
Kousteni
S
S
Zhou
H
H
McMahon
D J
DJ
Kode
A
A
Sliney
J
J
Shane
E
E
Silverberg
S J
SJ
Bilezikian
J P
JP
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D051929:CD146 Antigen / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007011:Hypoparathyroidism / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000627:therapeutic use*; D012044:Regression Analysis; D013972:Thyrotropin / Q000378:metabolism
D018952:Antigens, CD34; D051929:CD146 Antigen; D010281:Parathyroid Hormone; D015675:Osteocalcin; D013972:Thyrotropin