HUMAN MARROW STROMAL OSTEOBLAST-LIKE CELLS DO NOT SHOW REDUCED RESPONSIVENESS TO IN-VITRO STIMULATION WITH GROWTH-HORMONE IN PATIENTS WITH POSTMENOPAUSAL OSTEOPOROSIS

Decreased osteoblastic activity seems to play an important role in the pathogenesis of postmenopausal osteoporosis. The aim of the present study was to examine the direct effects of human growth hormone (GH) on proliferation and differentiation of osteoblastic cells obtained from patients with postmenopausal osteoporosis and age-matched normals and to compare the cellular responses induced by GH between the two groups. Osteoblast cultures (human marrow stromal osteoblast-like cells) were established from bone marrow aspirates obtained from 9 osteoporotic patients and 12 age-matched normals. Effects on cell proliferation and cell differentiation markers [alkaline phosphatase (AP)], procollagen type I propeptide (PICP), and osteocalcin] were assessed. GH stimulated H-3-thymidine incorporation into DNA in cell cultures of osteoporotic patients to a maximum of 158 +/- 14% of no-treatment controls (n = 9, P < 0.001) and to 203 +/- 52% (n = 9, P < 0.001) in normals. GH increased cell number as measured by methylene blue (MB) assay in cells of osteoporotic patients to 138 +/-% (P < 0.05, n = 7) and in normals to 138 +/- 12 (P < 0.05, n = 7). GH alone reduced cellular AP production: 61 +/- 3.8% (P < 0.05, n = 7) versus 65 +/- 16% (P < 0.05, n = 7) and cellular PICP production: 79 +/- 6% (P < 0.05, n = 7) versus 69 +/- 16% (n.s., n = 7), in cell cultures of osteoporotics and normals, respectively. 1,25-dihydroxy vitamin D, (1,25(OH)(2)D-3) (10(-9) M) alone increased AP production in cell cultures of osteoporotics to 193 +/- 23% (P < 0.01, n = 7) and to 266 +/- 51% (P < 0.05, n = 7) in cell cultures of normals. 1,25(OH)(2)D-3 had no effect on PICP production in either culture. Combining GH and 1,25(OH)(2)D-3 reduced 1,25(OH)(2)D-3-stimulated levels of AP and osteocalcin. No statistically significant differences were observed in cell proliferation or cell differentiation responses between cell cultures of osteoporotic patients and normals. Our results demonstrate that osteoblastic cells obtained from osteoporotic patients exhibit normal responsiveness to short-term stimulation with GH in vitro and do not support the hypothesis of the presence of major defects in osteoblastic responsiveness to stimuli in patients with osteoporosis.