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 s tudy 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 group s. Osteoblast cultures (human marrow stromal osteoblast-like cells) we re established from bone marrow aspirates obtained from 9 osteoporotic patients and 12 age-matched normals. Effects on cell proliferation an d cell differentiation markers [alkaline phosphatase (AP)], procollage n type I propeptide (PICP), and osteocalcin] were assessed. GH stimula ted H-3-thymidine incorporation into DNA in cell cultures of osteoporo tic 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 in creased 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 producti on: 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, re spectively. 1,25-dihydroxy vitamin D, (1,25(OH)(2)D-3) (10(-9) M) alon e 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 cu ltures 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 differentiati on responses between cell cultures of osteoporotic patients and normal s. Our results demonstrate that osteoblastic cells obtained from osteo porotic patients exhibit normal responsiveness to short-term stimulati on 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.