The risk of glucocorticoid-induced osteoporosis increases substantially with age but there is considerable individual variation. In recent studies we have shown that the effects of glucocorticoids on bone are dependent on autocrine actions of the enzyme 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1); expression of 11␤-HSD1 in osteoblasts (OBs) facilitates local synthesis of active glucocorticoids with consequent effects on osteoblastic proliferation and differentiation. Using primary cultures of human OBs, we have now characterized the age-specific variation in osteoblastic 11␤-HSD1 and defined enzyme kinetics and regulation using natural and therapeutic glucocorticoids. 11␤-HSD1 reductase activity (cortisone to cortisol conversion) was recognized in all OB cultures and correlated positively with age (r ‫؍‬ 0.58 with all cultures, p < 0.01, and n ‫؍‬ 18; r ‫؍‬ 0.87 with calcaneal-derived cultures, p < 0.001, and n ‫؍‬ 14). Glucocorticoid treatment caused a time-and dose-dependent increase in 11␤-HSD1 activity over control (e.g., dexamethasone [DEX; 1 M], 2.6-fold ؎ 0.5 (mean ؎ SE), p < 0.001, and n ‫؍‬ 16; cortisol (100 nM), 1.7-fold ؎ 0.1, p < 0.05, and n ‫؍‬ 14). Similar increases in 11␤-HSD1 mRNA expression were indicated using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analyses (3.5-fold with DEX, p < 0.01; 2.5-fold with cortisol, p < 0.05). The capacity of 11␤-HSD1 to metabolize the synthetic glucocorticoids prednisone and prednisolone was investigated in human OBs (hOBs) and fetal kidney-293 cells stably transfected with human 11␤-HSD1 cDNA. Transfected cells and hOBs were able to interconvert prednisone and prednisolone with reaction kinetics indistinguishable from those for cortisone and cortisol. To assess the in vivo availability of substrates for osteoblastic 11␤-HSD1, plasma cortisone and prednisone levels were measured in normal males before and after oral prednisolone (5 mg). The 9:00 a.m. serum cortisone levels were 110 ؎ 5 nmol/liter and prednisone levels peaked at 78 ؎ 23 nmol/liter 120 minutes after administration of prednisolone. Thus, therapeutic use of steroids increases substrate availability for 11␤-HSD1 in bone. These studies indicate that activation of glucocorticoids at an autocrine level within bone is likely to play an important role in the age-related decrease in bone formation and increased risk of glucocorticoid-induced osteoporosis. (J Bone Miner Res 2002;17: 979 -986)

Application of BIVAC to BV publications identified deficiencies in required study detail and delivery, especially for statistical analysis. Those deficiencies impact the veracity of BV estimates. BV data from BIVAC-compliant studies can be combined to deliver robust global estimates for safe clinical application.

CBX is able to inhibit rapidly the generation of active GC in human adipose tissue. Importantly, limiting GC availability in vivo has functional consequences including decreased glycerol release.

Data on biological variation are used for many purposes in laboratory medicine but concern exists over the validity of the data reported in some studies. A critical appraisal checklist has been produced by a working group established by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) to enable standardised assessment of existing and future publications of biological variation data. The checklist identifies key elements to be reported in studies to enable safe accurate and effective transport of biological variation data sets across healthcare systems. The checklist is mapped to the domains of a minimum data set required to enable this process.