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 explan ts of 30 patients with idiopathic osteoporosis and 45 control subjects in order to determine whether intrinsic abnormalities in osteoblast f unction may contribute to the decreased bone formation observed in thi s 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 E(1) (PGE(1)), basal and 1,25(OH)(2)D-3-stimulated alkaline phosphatas e activity and osteocalcin production. Results were compared amongst t hree subject groups: young controls less than 40 years old, older cont rols over 40 years old, and osteoporotics. Osteoporotic cells were fou nd in general to be fully active in vitro. There were no differences b etween osteoporotic and control cells in their basal levels of adenyla te cyclase, or alkaline phosphatase, in their growth rates, or cell mo rphology. The cyclic AMP (cAMP) response to PTH was significantly lowe r in osteoporotic cells (71%, p<0.01) and older control cells (64%, p< 0.005) relative to the response in cells from younger controls, sugges ting that the decreased responsiveness in osteoporotic cells was due t o subject age rather than the osteoporotic state. At the same time, th e cAMP responses to PGE, and cholera toxin were similar in cells from all three subject groups. The response to forskolin was reduced to abo ut 40% in osteoporotic cells compared with controls, but this was not mirrored by similar differences in the responses to PTH, PGE(1) or cho lera toxin, suggesting that the availability of catalytic subunits is not rate-limiting in these cells. 1,25(OH)(2)D-3-stimulated osteocalci n production was 220% higher in osteoporotics than in older controls, but the numbers tested were small and the difference did not reach sig nificance. The one significant abnormality we observed in osteoporotic cells was in alkaline phosphatase activity: 1,25(OH)(2)D-3-stimulated alkaline phosphatase activity was twofold higher in osteoporotics tha n in younger (p<0.05), older (p<0.05) and pooled controls (p<0.025). T he significance of this finding is unknown, but we postulate that it m ay reflect an intrinsic abnormality in osteoblast function in patients with idiopathic osteoporosis.