Relations between histologic indices of bone formation: Implications for the pathogenesis of spinal osteoporosis

Wall thickness, a major determinant of trabecular thickness, falls with age and falls further in osteoporosis. To estimate the importance of defective osteoblast recruitment in the pathogenesis of this defect, we compared various histologic indices of bone formation in iliac bone biopsies in three groups of subjects—healthy premenopausal women, healthy postmenopausal women, and patients with postmenopausal osteoporosis and at least one nontraumatic vertebral compression fracture. Indices that reflect the frequency of activation of bone remodeling and consequent birth rate of new teams of osteoblasts (osteoid surface, mineralizing surface, osteoblast surface, and bone formation rate, all expressed per unit of bone surface) were each higher in healthy subjects who were postmenopausal than in those who were premenopausal, but lower in osteoporotic than in normal postmenopausal women. In each group, the primary surface measurements were significantly correlated with each other, but the correlation was less close in those with osteoporosis. Indices that reflect the average collective performance of individual teams of osteoblasts (mineralizing surface and osteoblast surface per unit of osteoid surface, mineral apposition rate, adjusted apposition rate, and wall thickness) were all lower in postmenopausal than in premenopausal normal subjects, and even lower in those with postmenopausal osteoporosis. The parameters of the regression lines relating bone formation rate to osteoblast surface were essentially the same in each group, indicating that bone formation rate per unit of osteoblast surface was unaffected by age or menopause, and was the same in osteoporosis as in healthy subjects of similar age. We conclude that postmenopausal osteoporosis is characterized by a partial reversal of the menopause-related increases in histologic indices of bone formation that reflect activation frequency, and by an exaggeration of the age-related declines in the indices that reflect osteoblast team performance. Defective osteoblast recruitment makes a major contribution to the fall in wall thickness; this single defect can account for much of the age- and disease-related decline in osteoblast team performance.