AIMS: To analyse osteoblast function in 153 cases of established osteoporosis as previous work has indicated that osteoporosis is a heterogeneous condition characterised by different patterns of osteoclast and osteoblast dysfunction. METHODS: Histomorphometric data from 153 cases with established osteoporosis was used to analyse osteoblast function, using the following parameters: osteoblast number was assessed using the ratio of osteoblast surface to bone surface (ObS:BS); the percentage of active osteoblasts was assessed by using mineralising surface as a proportion of osteoid surface (sLS + dLS/OS); and the efficiency of active osteoblasts was assessed using the ratio of double to total labelled surface (dLS:tLS). The values of each parameter were standardised using age and sex matched control data and a three dimensional matrix was used to identify groups of patients with similar patterns of altered function. RESULTS: The largest group (60 cases) showed a reduction in all three parameters, while a small group (9 cases) had normal osteoblast function. However, one group showed reduction in osteoblast number only (23 cases), while another group showed a normal number of osteoblasts but both reduced percentage and efficiency of activity (14 cases). The results also suggest that efficiency of activity falls first and that this eventually leads to exit from the active pool. CONCLUSIONS: These results demonstrate the presence of heterogeneity of osteoblast dysfunction in osteoporosis, indicating that the disease is caused by interference at a variety of target sites along the pathway of osteoblast proliferation, differentiation, and activation. Greater understanding of this pathway and of the variety of alterations in the pathway that can occur in osteoporosis may allow more focused therapy for different patient groups identified on the basis of histomorphometric analysis.