Primary research

Role of cortisol in the pathogenesis of postmenopausal osteoporosis: relationship to bone structure

Excess glucocorticoids are well recognised as a cause of osteoporosis; they inhibit osteoblast function and increase osteoblast and osteocyte apoptosis resulting in thinning of the trabeculae. The circadian rhythm of bone turnover, which is linked to cortisol rhythm, is abnormal in osteoporosis. Furthermore, some studies show abnormal cortisol metabolism in osteoporosis. The aim of our study was to evaluate the day–night rhythm of cortisol and to relate cortisol levels to bone micro-structure.

Methods: Postmenopausal women with vertebral fractures and a hip or spine BMD T-score <−1.0 were recruited (Group 1, n=30) In addition, two sex-/age-matched control groups with i) BMD matched to those in Group 1 (Group 2, n=30), and ii) normal BMD (Group 3, n=30) were studied. Salivary cortisol was measured at 0900 and 2300 h. Lumbar spine and hip BMD were measured by DXA, prevalent vertebral fractures were identified by VFA, and bone micro-structure in the distal radius and tibia was examined by high resolution peripheral quantitative computed tomography (HR-pQCT). Vertebral fractures were confirmed on plain radiography using the algorithm-based qualitative method.

Results: Between group differences in hip (P<0.001) and spine (P<0.001) T-scores were detected by ANOVA. Post-hocScheffe tests revealed that spine and hip T-scores for Groups 1 and 2 did not differ, whilst T-scores for Group 3 were higher (P<0.001). Mean (S.D.) 0900 h salivary cortisol was significantly elevated in the vertebral fracture group (9.2 (4.7), 6.6 (5.0)and 6.4 (4.1) nmol/l ANOVA by trend P=0.034) and this correlated significantly with radial total volumetric BMD (Spearman’s ρ−0.78; P=0.01) and trabecular thickness (Spearman’s ρ−0.73; P=0.026) in the vertebral fracture group. 2300 h salivary cortisol levels were not related to BMD or bone micro-structure.

Conclusion: Our findings show that the diurnal cortisol rhythm may possibly be altered in those women with vertebral fractures. Higher morning cortisol could contribute to an increased risk of vertebral fractures through thinning of the trabeculae.