title: Increased serum osteoprotegerin in patients with primary adrenal insufficiency receiving conventional hydrocortisone substitution.
abstract: Patients treated for primary adrenal insufficiency (PAI) are at risk of steroid over-replacement, which may affect their skeleton. The study was aimed to investigate the effect of steroid substitution on serum osteoprotegerin and receptor activator of nuclear factor kappa-beta ligand (RANKL) levels in relation to bone mineral density (BMD) in PAI. Eighty patients (mean age 47.2±14.5 years, mean hydrocortisone dose 0.49±0.14 mg/kg/day) and 63 healthy subjects were included. Serum osteoprotegerin, RANKL, 25-hydroxyvitamin D₃, calcium, phosphate, alkaline phosphatase, intact parathormone, and dehydroepiandrosterone-sulfate levels were evaluated in patients and controls. BMD was assessed in affected subjects using dual-energy X-ray absorptiometry. Mean osteoprotegerin concentration in PAI patients appeared significantly higher vs. controls (p=0.002), while RANKL levels were similar (p=0.430). Serum osteoprotegerin increased with age (p<0.001), but showed no correlation with daily hydrocortisone dose. Osteoprotegerin was negatively correlated with serum dehydroepiandrosterone-sulfate (p=0.008) and with BMD at the lumbar spine (p<0.001) and femoral neck (p=0.003). RANKL correlated negatively with PAI duration (p=0.029) and positively with daily hydrocortisone dose (p=0.018). Lumbar spine osteoporosis and osteopenia were found in 12 and 31 patients, respectively, whereas in femoral neck: in 5 and 33 individuals. Patients with osteoporosis displayed higher osteoprotegerin levels, but after the age-adjustment the correlation was lost. In conclusion, increased osteoprotegerin in PAI might reflect a compensatory response to enhanced bone resorption due to exogenous steroid excess and/or result from a deficit in adrenal androgens. RANKL levels remain within normal range on standard steroid replacement.
authors: Department of Endocrinology and Metabolism, University of Medical Sciences, Poznan, Poland. mfichna@man.poznan.pl
authors: M
authors: M
authors: Fichna
authors: M
authors: M
authors: Zurawek
authors: P
authors: P
authors: Fichna
authors: M
authors: M
authors: Gryczynska
authors: J
authors: J
authors: Nowak
authors: M
authors: M
authors: Ruchala
mesh_terms: D015502:Absorptiometry, Photon; D000224:Addison Disease / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood; D012044:Regression Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D006854:Hydrocortisone