Bone Mineral Density Is Not Significantly Reduced in Adult Patients on Low-Dose Glucocorticoid Replacement Therapy

The Journal of Clinical Endocrinology & Metabolism, Jan 2012

Patients with primary adrenal insufficiency (PAI) and patients with congenital adrenal hyperplasia (CAH) receive glucocorticoid replacement therapy, which might cause osteoporosis.

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Bone Mineral Density Is Not Significantly Reduced in Adult Patients on Low-Dose Glucocorticoid Replacement Therapy

Received July Bone Mineral Density Is Not Significantly Reduced in Adult Patients on Low-Dose Glucocorticoid Replacement Therapy K. R. Koetz 0 M. Ventz 0 S. Diederich 0 M. Quinkler 0 0 Department of Clinical Endocrinology (K.R.K., M.V., M.Q.), Charit e ́ Campus Mitte, Charite ́ University Medicine , D-10117 Berlin, Germany; and Endokrinologikum (S.D.), D-10117 Berlin , Germany Context: Patients with primary adrenal insufficiency (PAI) and patients with congenital adrenal hyperplasia (CAH) receive glucocorticoid replacement therapy, which might cause osteoporosis. Objectives: Questions addressed by this study were: 1) Is bone mineral density (BMD) reduced in PAI and CAH on lower glucocorticoid doses than previously reported? 2) Is BMD in PAI influenced by the type of glucocorticoid used? and 3) Does DHEA treatment affect BMD in PAI women? Design and Patients: We conducted a prospective, cross-sectional study including 81 PAI patients and 41 CAH patients. Main Outcome Measures: BMD was measured by dual-energy x-ray absorptiometry. Serum levels of bone turnover markers, minerals, vitamins, hormones, and urinary crosslinks were measured. Results: PAI and CAH patients received average daily hydrocortisone doses of 12.0 2.7 mg/m2 (range, 4.9 -19.1) and 15.5 7.8 mg/m2 (range, 5.7-33.7), respectively. BMD varied within the normal reference range ( 2 to 2) in both cohorts. However, lower Z-scores for femoral neck and Ward's region were found in CAH compared to PAI women, but not in men. Prednisolone treatment showed significant lower osteocalcin levels and lower Z-scores for lumbar spine and femoral neck compared to PAI patients on hydrocortisone. PAI women treated with DHEA had significantly lower urinary collagen crosslinks and bone alkaline phosphatase, and significantly higher Z-scores in lumbar spine and femoral Ward's region compared to non-DHEA-treated women. Conclusions: Adult PAI and CAH patients on low glucocorticoid doses showed normal BMD within the normal reference range. The use of longer acting prednisolone resulted in significantly lower BMD in PAI. In addition, DHEA treatment may have a beneficial effect on bone in Addison's women. (J Clin Endocrinol Metab 97: 85-92, 2012) - P dison’s disease) and patients with congenital adrenal atients with primary adrenal insufficiency (PAI; Adhyperplasia (CAH) both lack sufficient endogenous production of glucocorticoids ( 1, 2 ). The lifelong replacement therapy is given daily in a single or divided dose, sometimes thrice daily, depending on which glucocorticoid type is taken (3). However, the daily intake of glucocorticoids in PAI and CAH still tends to be more than the normal endogenous production in healthy subjects ( 4, 5 ), especially in CAH patients aiming at suppression of adrenal androgen production. Despite the fact that chronic treatment with glucocorticoids is known to influence bone homeostasis by direct suppression of osteoblastic activity (6), inhibition of intestinal calcium absorption with secondary hyperparathyroidism, and increased bone resorption by osteoclasts ( 7 ), bone mineral density (BMD) measurements are not recommended for regular monitoring in adrenal insufficiency ( 2, 8 ). Abbreviations: AP, Alkaline phosphatase; BAP, bone AP; BMD, bone mineral density; BMI, body mass index; CAH, congenital adrenal hyperplasia; CTX, -crosslaps; DHEA, dehydroepiandrosterone; GC-dose, glucocorticoid dose; GC-packyears, cumulative amount of glucocorticoid intake (hydrocortisone-equivalent dose) since diagnosis (in grams); NTX, urinary collagen crosslinks; PAI, primary adrenal insufficiency; SDS, SD score. jcem.endojournals.org Until now, few studies focused on this subject. Most were limited by small patient numbers and showed inconsistent findings between BMD, disease duration, glucocorticoid type, and daily dose. Some studies reported reduced BMD in all PAI patients ( 9 ), some only in postmenopausal women ( 10, 11 ) or only in men ( 12, 13 ), whereas others studies found no significant differences in BMD in both sexes ( 14, 15 ). Recently, Lovas et al. (16) showed in a large retrospective cohort of PAI patients significant lower BMD at the femoral neck and lumbar spine compared with healthy subjects. However, the major disadvantage of former studies was the rather high glucocorticoid doses ( 30 mg hydrocortisone equivalent/day) used in those patients. The few studies regarding the skeletal health of adult patients with CAH also showed contrasting findings. Several studies reported no significant differences in BMD between patients with CAH and controls ( 17–22 ), whereas others found reduced BMD in all or some subpopulations of CAH patients ( 23–32 ). The inconsistent findings of these studies may be related to heterogeneous populations and methods, especially with respect to age and glucocorticoid regimes. In addition, there has been no literature comparing BMD of adult patients with Addison’s disease to adult CAH patient (...truncated)


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Koetz, K. R., Ventz, M., Diederich, S., Quinkler, M.. Bone Mineral Density Is Not Significantly Reduced in Adult Patients on Low-Dose Glucocorticoid Replacement Therapy, The Journal of Clinical Endocrinology & Metabolism, 2012, pp. 85-92, Volume 97, Issue 1, DOI: 10.1210/jc.2011-2036