Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease.
BACKGROUND
Osteoporosis is an important, frequently unrecognized consequence of hypercortisolism.


OBJECTIVE
To evaluate whether the age of onset of hypercortisolism influences its effects on bone mass and turnover.


METHODS
10 with childhood-onset (co) and 18 with adulthood-onset (ao) Cushing's disease (CD); 28 age-, sex- and body mass index (BMI)-matched healthy subjects served as controls.


METHODS
Open, cross-sectional controlled.


METHODS
Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC), and urinary N-telopeptides of type I collagen (Ntx) levels.


RESULTS
BMD at lumbar spine was significantly lower in all CD patients than in controls (Z score, -2.3 +/- 0.1 vs. -0.2 +/- 0.01; P < 0.001). co-CD and ao-CD patients had similar values of bone mass when expressed as Z score (-2.6 +/- 0.4 vs. -2.1 +/- 0.2; P = 0.27) or as BMD (0.728 +/- 0.03 vs. 0.78 +/- 0.03 g/cm2; P = 0.25). In particular, osteoporosis was observed in 16 patients (57.1%) [eight adolescents (80%) and eight adults (44.4%)] and none of the controls; osteopenia was found in two co-CD patients (20%) and none of the healthy adolescents, 10 ao-CD patients (55.6%) and four healthy adults (14.3%) (chi2 = 7.87, P < 0.01; chi2 = 2.99, P = 0.09, respectively). In co-CD and ao-CD patients, serum OC levels were similar and significantly lower than in controls (P < 0.01); urinary Ntx levels were significantly higher than in controls (P < 0.001) and were significantly higher in co-CD than in ao-CD patients (P < 0.001). No significant correlation was found between urinary cortisol levels, serum cortisol and age and lumbar Z score values, while a significant correlation was found between Ntx levels and disease duration (r = 0.434; P = 0.021) and plasma cortisol (r = 0.440; P = 0.019).


CONCLUSIONS
Cushing's disease causes bone loss and abnormalities of bone turnover both in childhood-onset and in adulthood-onset patients. A strict follow-up of bone mass and turnover is mandatory in all patients with Cushing's disease to prevent fractures later in life and specific treatment for bone loss is strongly suggested.
Di Somma
Carolina
C
Department of Molecular and Clinical Endocrinology and Oncology, CNR Biomorphological and Functional Sciences, 'Federico II' University of Naples and Servizio di Endocrinologia Pediatrica, Ospedale Regionale per le Microcitemie, Cagliari, Italy.
Pivonello
Rosario
R
Loche
Sandro
S
Faggiano
Antongiulio
A
Marzullo
Paolo
P
Di Sarno
Antonella
A
Klain
Michele
M
Salvatore
Marco
M
Lombardi
Gaetano
G
Colao
Annamaria
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D016723:Bone Remodeling; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000652:urine; D012044:Regression Analysis
D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen