Relative potencies of 1,25-(OH)(2)D-3 and 19-Nor-1,25-(OH)(2)D-2 on inducing differentiation and markers of bone formation in MG-63 cells

19-Nor-1,25-(OH)(2)D-2, an analog of 1,25-(OH)(2)D-3, is used to treat seco ndary hyperparathyroidism because it suppresses parathyroid hormone synthes is and secretion with lower calcemic and phosphatemic activities. 19-Nor-1, 25(OH)(2)D-2 is approximately 10 times less active than 1,25(OH)(2)D-3 in p romoting bone resorption, which accounts in part for the low potency of thi s analog in increasing serum calcium and phosphorus. Concern that 19-nor-1, 25-(OH)(2)D-2 also could be less potent than 1,25-(OH)(2)D-3 on bone format ion led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)(2)D-3 and 19-nor-1,25 -(OH)(2)D-2 had a similar potency in upregulating vitamin D receptor conten t and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Tim e-course and dose-response studies on 1,95-(OH)(2)D-3 and 19-nor-1,25-(OH)( 2)D-2 induction of the marker of bone formation, osteocalcin, showed overla pping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and tran sforming growth factor-beta, an enhancer of 1,25-(OH)(2)D-3-induced ALP act ivity in this cell line. Transforming growth factor-beta alone had no effec t, whereas 1,25-(OH)(2)D-3 and 19-nor-1,25-(OH)(2)D-2 increased ALP activit y similarly These studies demonstrate that 19-nor-1,25-(OH)(2)D-2 has the s ame potency as 1,25-(OH)(2)D-3 not only in inducing vitamin D receptor cont ent, osteocalcin levels, and ALP activity but also in controlling osteoblas tic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)(2)D-2 would hav e deleterious effects on bone remodeling.