Change in bone mineral density at one year following glucocorticoid withdrawal in kidney transplant recipients.

Glucocorticoid (GC) therapy induces deleterious effects on the skeleton in kidney transplantation but studies of GC discontinuation in this population are limited. This study evaluated changes in areal bone mineral density (BMD) with GC withdrawal. Subjects were enrolled one yr after renal transplantation and randomized to continue or stop prednisone; all subjects continued cyclosporine and mycophenolate mofetil. BMD measured by dual-energy X-ray absorptiometry was performed at enrollment and repeated at one yr and values were standardized. Mean ± standard deviation of annualized change in standardized BMD between GC withdrawal vs. continuation group at the lumbar spine was +4.7% ± 5.5 vs. +0.9% ± 5.3 (p = 0.0014); total hip +2.4% ± 4.2 vs. -0.4% ± 4.2 (p = 0.013), and femoral neck +2.1% ± 4.6 vs. +1.0% ± 6.0 (p = 0.37). There was no confounding by prednisone dose prior to enrollment, change in creatinine clearance, weight, or use of bone-active medications following study entry. Multivariate analysis determined that the change in BMD was positively associated with baseline alkaline phosphatase and creatinine clearance and negatively associated with baseline BMD. BMD improves with GC withdrawal after renal transplantation, and this gain in BMD is dependent on the baseline bone turnover, renal function, and BMD.

Epidemiology of fracture risk in the Women's Health Initiative.

Osteoporosis is one of the most disabling consequences of aging in women. Strategies that permit earlier identification of women at risk for fracture are needed. The Women's Health Initiative has extended our knowledge of clinical risk factors and biomarkers of fracture risk in postmenopausal women. Based upon 11 clinically available risk factors (age, race/ethnicity, self-reported health, weight, height, physical activity, parental hip fracture, fracture history after age 54, current smoking, corticosteroid use, and history of treated diabetes), an algorithm has been developed to predict 5-year hip fracture risk. Biomarkers including low vitamin D or bioavailable testosterone and/or high cystatin C or sex hormone-binding globulin also predict risk for hip fracture independent of clinical risk factors. To address the growing incidence of fractures in minority women, clinical risk factors for fracture have been identified. These data demonstrate that we can better identify women, irrespective of race or ethnicity, at risk for fracture.

Increased 2-hydroxylation of estrogen in women with a family history of osteoporosis.

Recent studies indicate that women with predominant estrogen metabolism through the 2-hydroxyl (inactive) pathway have lower bone mineral density (BMD) compared with those with predominant 16alpha-hydroxylation (active). Although many factors have been identified to affect estrogen metabolism, the role of a family history of osteoporosis remains unknown. The objective of this study was to investigate the influence of family history of osteoporosis and other clinical factors on estrogen hydroxylation. This was a cross-sectional study conducted in a university-based research center from May 2002 to February 2004. The participants included 175 otherwise healthy postmenopausal women at least 1 yr from the last menstrual period. Main outcome measures were urinary estrogen metabolites and BMD of the spine and femur. Women with a family history of osteoporosis had significantly higher log-transformed ratios of 2-hydroxyestrone/16alpha-hydroxyestrone (0.303 +/- 0.03 vs. 0.226 +/- 0.03; P = 0.04) and 2-methoxyestrone/16alpha-hydroxyestrone (0.024 +/- 0.02 vs. -0.036 +/- 0.02; P = 0.03) compared with women without family history. As expected, these women also had significantly lower BMD at the total femur, trochanter, and intertrochanter. Surprisingly, calcium intake positively correlated with metabolite levels, and women in the highest quartile of calcium intake had the highest levels of urinary metabolites. In conclusion, women with a positive family history of osteoporosis have predominant estrogen metabolism through the inactive 2-hydroxyl pathway; thus, the increased risk of osteoporosis in those with family history may in part be related to inherited differences in estrogen metabolism. The finding that calcium intake modulates estrogen hydroxylation has never been reported and thus deserves additional investigation.