Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Introduction: Patients with 21-hydroxylase deficiency (21OHD) assume a lifelong glucocorticoid (GC) therapy. Excessive GC treatment increases the risk of osteoporosis and bone fractures, even though the role of substitutive therapy is not fully established: we analyzed the effect of GC dose on bone metabolism and bone mineral density (BMD) over time in patients with 21OHD. Methods: We studied bone metabolism markers and BMD in 38 adult patients with 21OHD (19-47 years, 24 females and 14 males) and 38 matched healthy control. In 15 patients, BMD data were available at both baseline and after a long-term follow-up. Results: BMD was lower in patients than in controls at lumbar spine (0.961 +/- 0.1 g/cm(2) vs 1.02 +/- 0.113 g/cm(2), P = 0.014) and femur neck (0.736 +/- 0.128 g/cm(2) vs 0.828 +/- 0.103 g/cm(2), P = 0.02); otherwise, after height correction, only femoral neck BMD was lower in patients (0.458 +/- 0.081 g/cm(2) vs 0.498 +/- 0.063 g/cm(2), P = 0.028). In those 21OHD subjects with at least 10 years follow-up, we observed an increase in lumbar BMD (P = 0.0429) and a decrease in femur neck BMD values (P = 0.004). Cumulative GC dose was not related to bone metabolism or BMD. No patient experienced clinical fragility fractures. Conclusions: BMD values are decreased in patients with 21OHD, which are in part explained by decreased height, but not by the dose of glucocorticoids. Nevertheless, bone status should be carefully monitored in patients with 21OHD.