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)
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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)