In vitro study of osteoblastic cells from patients with idiopathic osteoporosis and comparison with cells from non-osteoporotic controls.
We have examined bone cells derived from iliac crest trabecular explants of 30 patients with idiopathic osteoporosis and 45 control subjects in order to determine whether intrinsic abnormalities in osteoblast function may contribute to the decreased bone formation observed in this disease. Bone cells isolated from all subjects expressed several in vitro characteristics of the osteoblast phenotype including adenylate cyclase responsiveness to parathyroid hormone (PTH) and prostaglandin E1 (PGE1), basal and 1,25(OH)2D3-stimulated alkaline phosphatase activity and osteocalcin production. Results were compared amongst three subject groups; young controls less than 40 years old, older controls over 40 years old, and osteoporotics. Osteoporotic cells were found in general to be fully active in vitro. There were no differences between osteoporotic and control cells in their basal levels of adenylate cyclase, or alkaline phosphatase, in their growth rates, or cell morphology. The cyclic AMP (cAMP) response to PTH was significantly lower in osteoporotic cells (71%, p < 0.01) and older control cells (64%, p < 0.005) relative to the response in cells from younger controls, suggesting that the decreased responsiveness in osteoporotic cells was due to subject age rather than the osteoporotic state. At the same time, the cAMP responses to PGE1 and cholera toxin were similar in cells from all three subject groups. The response to forskolin was reduced to about 40% in osteoporotic cells compared with controls, but this was not mirrored by similar differences in the responses to PTH, PGE1 or cholera toxin, suggesting that the availability of catalytic subunits is not rate-limiting in these cells. 1,25(OH)2D3-stimulated osteocalcin production was 220% higher in osteoporotics than in older controls, but the numbers tested were small and the difference did not reach significance. The one significant abnormality we observed in osteoporotic cells was in alkaline phosphatase activity: 1,25(OH)2D3-stimulated alkaline phosphatase activity was twofold higher in osteoporotics than in younger (p < 0.05), older (p < 0.05) and pooled controls (p < 0.025). The significance of this finding is unknown, but we postulate that it may reflect an intrinsic abnormality in osteoblast function in patients with idiopathic osteoporosis.
Wong
M M
MM
Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
Rao
L G
LG
Ly
H
H
Hamilton
L
L
Ish-Shalom
S
S
Sturtridge
W
W
Tong
J
J
McBroom
R
R
Josse
R G
RG
Murray
T M
TM
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology*; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D012016:Reference Values
D010281:Parathyroid Hormone; D015675:Osteocalcin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002117:Calcitriol