Role of sclerostin and dickkopf-1 in the dramatic alteration in bone mass acquisition in adolescents and young women with recent anorexia nervosa.
BACKGROUND
The nutritional deprivation of adolescent girls with anorexia nervosa (AN) reduces bone mass acquisition. A better understanding of this process would improve the medical treatment of bone alteration and its long-term consequences.


OBJECTIVE
The first aim was to model the bone mass acquisition in young women with AN. The second aim was to identify the clinical and biological factors associated with bone demineralization and investigate the potential role of sclerostin and dickkopf-1 protein (DKK-1).


METHODS
Ninety-eight AN patients (mean age 18.2 ± 2.6 years) and 63 age-matched controls were enrolled in this study. Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry. Calciotropic hormones, bone turnover markers, sclerostin, DKK-1, and growth factors were concomitantly evaluated.


RESULTS
The aBMD was significantly reduced at all bone sites in AN patients vs controls (range, -3.3% at the radius to -12.1% for total proximal femur). Bone formation markers IGF-1 and DKK-1 were significantly decreased in AN patients, whereas PTH, sclerostin, and the bone resorption markers were increased. In patients, the AN duration, amenorrhea, weight, body mass index, fat mass, and fat-free soft tissue were negatively correlated with aBMD, whereas the age of AN onset was positively correlated. Multiple regression analysis revealed that the duration of amenorrhea was the independent factor most negatively associated with aBMD at all bone sites except the radius.


CONCLUSIONS
This case-control study demonstrated a dramatic reduction in aBMD, reinforced for the first time by our models, and indicates the need for early, systematic, and adapted bone mass monitoring. Moreover, appropriate treatment should be started early in patients with AN. Increased secretion of sclerostin suggests that it may be a target for pharmacological action.
Service de Médecine Nucléaire (L.M., D.M.-G.), Hôpital Lapeyronie, Centre Hospitalier Regional Universitaire (CHRU) Montpellier et Université Montpellier 1 (UMI); Service d'Hormonologie (L.M., P.P., F.P., C.S.) et Service de Rhumatologie (E.T.), Departement d'Endocrinologie, Diabète, Nutrition (P.L., J.B., E.R.), and Unité de Recherche Clinique et Epidémiologie (H.B., M.-C.P.), Hôpital Lapeyronie, CHRU Montpellier; Département d'Urgence et Post-Urgence Psychiatrique (S.G., P.C.), Hôpital Lapeyronie, CHRU Montpellier and UM1, Inserm Unité (U) 1061; Physiologie et Médecine Expérimentale du Cœur et des Muscles (L.M.), Inserm U1046, UM1 and UM2; Centre d'Investigation Clinique (CIC) Inserm 1411 (M.-C.P., E.R.), Hôpital Gui de Chauliac, CHRU Montpellier; Unité d'Endocrinologie et Gynécologie Pédiatrique (F.P., C.S.), Département de Pédiatrie, Hôpital Arnaud de Villeneuve, CHRU Montpellier et UM1; and Institut de Génomique Fonctionnelle (E.R.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 5203/Inserm U661/UM1 and UM2, 34295 Montpellier, France; and Département de Pédiatrie (L.G.), Hôpital Caremeau, CHRU Nîmes, 30000 Nîmes, France.
Laurent
L
Maïmoun
Sébastien
S
Guillaume
Patrick
P
Lefebvre
Pascal
P
Philibert
Helena
H
Bertet
Marie-Christine
MC
Picot
Laura
L
Gaspari
Françoise
F
Paris
Philippe
P
Courtet
Eric
E
Thomas
Denis
D
Mariano-Goulart
Jacques
J
Bringer
Eric
E
Renard
Charles
C
Sultan
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood* / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000494:pharmacology; D005260:Female; D005819:Genetic Markers / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D003276:Contraceptives, Oral; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human