Altered trabecular architecture induced by Corticosteroids: A Bone Histomorphometric Study

Abstract

Prolonged corticosteroid (CS) therapy induces osteoporosis and fractures. Osteoporosis is characterized at the histomorphometric level by reduced bone volume (BV/TV) and disruption of the three-dimensional (3D) trabecular architecture. Several stereological methods have been proposed to characterize these alterations: measurements of trabecular thickness and trabecular number, star volumes, interconnectivity index (ICI) of the bone marrow spaces, and trabecular bone pattern factor (TBP(f)). These methods were computerized with a single program running on an image analyzer to evaluate the bone changes in a series of iliac biopsies performed on 31 male patients. All of them were asthmatic and had received CS for a long period of time. BV/TV was reduced when compared with age-matched controls. In the CS-treated population, exponential relationships were obtained between bone volume and the different connectivity parameters. The various methods used to measure connectivity were well correlated. When the population was divided into two groups (BV/TV greater or less than an 11% threshold), the architectural disturbances were found to imply two mechanisms. A progressive decline in trabecular thickness was noted in both groups versus controls. Trabecular perforations were not established in the group with BV/TV> 11% with the star volume or ICI, although some alterations were detected by trabecular bone pattern factor measurement. However, perforations were revealed in the group with BV/TV < 11% by all the different methods. Perforations seemed to occur when the trabecular thickness was below 70 mu m. This strongly suggests that bone histomorphometry should take into consideration bone volume in combination with detailed 3D descriptors of the trabecular architecture. Several histological methods need to be used in combination to appreciate the 3D architecture of trabecular bone.

Validation of the sheep as a large animal model for the study of vertebral osteoporosis

“…In the iliac crest and the lumbar spine this was due mainly to thinning of existing trabecular elements rather than a decrease in connectivity. This has also been reported after corticosteroid therapy in humans and rats [6,26]. In contrast there was thinning as well as wholesale loss of trabeculae (and hence connectivity) in the proximal femur, more like the situation observed in postmenopausal osteoporosis [1].…”

Changes in osteocyte density correspond with changes in osteoblast and osteoclast activity in an osteoporotic sheep model

“…Bone loss in the IC was due mainly to thinning of existing trabecular elements rather than a decrease in connectivity since there was no significant change in Tb.Sp and Tb.N between the control and osteoporotic groups. This type of bone reduction has also been reported after corticosteroid therapy in humans and rats [30,31]. In contrast, bone in LS showed thinning, as well as loss of trabeculae and hence connectivity, that is more often observed in human postmenopausal osteoporosis [32].…”

Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis

“…A further possibility is the effects of these agents on skeletal architecture, which appears to differ from the effects of gonadal deficiency at sites of cancellous bone. 47,278 It is also suggested that glucocorticoids affect osteocyte viability 279 and therefore might induce alterations in the material properties of bone.…”