The etiology of primary
osteoporosis in young and middle-aged men is unknown. We have studied osteoblast function in cells derived from men with idiopathic
osteoporosis and in control cells from age-matched men with
osteoarthrosis. Osteoblasts were isolated from transiliac bone biopsies. Osteoblast function was measured as
vitamin D-stimulated
osteocalcin production and production of
cytokines and factors involved in osteoclast activation and bone formation. Cell proliferation was measured as (3)H-thymidine incorporation.
Parathyroid hormone-related peptide (
PTHrP)
mRNA was measured using
reverse-transcriptase polymerase chain reaction. In osteoporotic men, bone mineral density at the femoral neck was correlated to in vitro production of
osteocalcin. Osteoblasts from osteoporotic men produced significantly less
osteocalcin after
vitamin D stimulation but had increased production of
macrophage colony-stimulating factor (
M-CSF) compared to controls. The
osteocalcin response was negatively correlated to production of
M-CSF,
interleukin-6, and C-terminal propeptide of
type I collagen. Basal (3)H-thymidine incorporation was similar in cells from osteoporotic patients and controls.
PTHrP (10(-9 )M) significantly increased cell proliferation in control cells but not in osteoporotic cells. Basal
PTHrP mRNA levels were significantly higher in osteoporotic cells than in cells from controls. The results are in agreement with previous histomorphologic studies indicating that men with idiopathic
osteoporosis have an osteoblast dysfunction with decreased
osteocalcin production and increased production of factors stimulating osteoclast activation. This indicates a catabolic cellular metabolic balance leading to negative bone turnover, resulting in
osteoporosis. The cause of such cellular dysfunction needs further evaluation.