AbstractOsteoblasts undergo changes both in shape (progressive flattening) and function (progressive decline in matrix synthesis) during their life span. Nuclear volume, apart from changing systematically during their cell cycle, is believed to be a general index of cell vigor. Accordingly, we measured the nuclear profile area of osteoblasts classified as pre (Group I), cuboidal (Group II), intermediate (Group III), and terminal (Group IV) in iliac cancellous bone in 6 premenopausal normals, mean age in years (SD) 40.2 (4.8), 5 postmenopausal normals, age 65.8 (2.4), 15 postmenopausal osteoporotics, age 65.3 (4.9), 5 patients with fluorideinduced osteomalacia, age 69.2 (5.0), and two patients with endemic fluorosis, age 70.5 (5.5). A total number of 4,085 osteoblast nuclei were examined and measured. In each group there was a systematic decline in nuclear profile area through stages I-IV, corresponding to an average decline in nuclear volume of greater than 90%. The major difference among groups was that in type II (cuboidal) osteoblasts, nuclear profile area was significantly greater in premenopausal normals than in the other four groups, which did not differ significantly. The effect seems to be related to age, rather than to disease or treatment. The functional significance of this age-related morphologic change remains to be determined, but it may be related to the decline in apposition rate with age. (The J Histotechnol19:313–315, 1996)