Severe impairment of bone mass and turnover in Cushing’s disease: comparison between childhood‐onset and adulthood‐onset disease

Somma, Carolina Di; Pivonello, Rosario; Loche, Sandro; Faggiano, Antongiulio; Marzullo, Paolo; Sarno, Antonella Di; Klain, Michele; Salvatore, Marco; Lombardi, Gaetano; Colao, Annamaria

doi:10.1046/j.0300-0664.2001.01454.doc.x

Cited by 70 publications

(42 citation statements)

References 41 publications

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“…It is well known that high circulating glucocorticoid levels lead to severe impairment of bone mass and turnover (Di Somma et al, 2002). The difference in serum cortisol levels between AN patients and controls was, however, rather small (Table 1) and serum cortisol levels had no significant independent effect on bone turnover (Results section).…”

Section: Discussionmentioning

confidence: 87%

Body mass index and disease duration are predictors of disturbed bone turnover in anorexia nervosa. A case–control study

et al. 2003

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Objective: To characterize the influence of body mass index (BMI), body composition, hormonal factors and disease duration on bone metabolism markers in anorexia nervosa (AN) patients. Design: Case-control study with 51 AN patients and 51 controls matched for age, sex and body height. Assessment of anthropometric and bioimpedance data, and of biochemical serum parameters and of oral contraceptives use. Results: Patients had a lower BMI, lower fat mass, lower fat-free mass and lower muscle mass (MM) compared to the controls (all P values o0.001). Moreover, serum levels of osteocalcin (bone formation marker) were lower while serum C-telopeptide concentrations (CTx; bone resorption marker) and the CTx/osteocalcin ratio (an index reflecting the balance of bone remodeling) were higher in the AN patients compared to the controls (Po0.01-0.001). In addition, patients had enhanced serum calcium and cortisol levels and reduced serum levels of thyroid hormones, insulin, and leptin (P values o0.05-0.001). Mean disease duration was 91713 months. In a multiple regression analysis, BMI (Po0.0001), MM (Po0.005) and duration of the disease (Po0.005) were independent predictors of the CTx/osteocalcin ratio in the AN patients. There was a nonlinear association between BMI and the CTx/osteocalcin ratio of r ¼ À0.72 (Po0.001) in the AN patients, but only a weak relation of r ¼ À0.27 (Po0.05) between these parameters in the control subjects. Use of oral contraceptives had no effect on the CTx/ osteocalcin ratio, neither in AN patients nor in controls. Conclusions: Data indicate an uncoupling of bone formation and bone resorption in AN, which is primarily the result of a low BMI and influenced by the duration of the disease.

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Section: Discussionmentioning

confidence: 87%

Body mass index and disease duration are predictors of disturbed bone turnover in anorexia nervosa. A case–control study

et al. 2003

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“…Leptin has been hypothesized to participate in the activation of the adrenal axis to conserve metabolic fuels in the face of energy deprivation. Glucocorticoids are known to have deleterious effects on bone mass (19), while insulin is thought to act as an anabolic agent on bone (20). In anorectic subjects, a condition of increased bone resorption is consistently accompanied by increased cortisol levels and decreased insulinaemia.…”

Section: Discussionmentioning

confidence: 99%

“…However, the absence of a relationship suggests that neither cortisol nor insulin played a direct role in increasing bone resorption. Greater concentrations of cortisol and longer exposure to hypercortisolaemia might be required for glucocorticoids to exert significant negative effects on bone resorption (19).…”

Section: Discussionmentioning

confidence: 99%

Relationships between serum leptin and bone markers during stable weight, weight reduction and weight regain in male and female judoists

Prouteau¹,

Benhamou²,

Courteix³

2006

eur j endocrinol

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Objective: Despite a preliminary understanding of leptin -skeletal interactions, data in humans are inconsistent and the exact roles of leptin on bone metabolism have not yet been defined. The aim of this study was to examine the possible role of leptin in the regulation of bone metabolism in healthy, physically trained adults. Methods and Design: Body composition and bone mass (dual-energy X-ray absorptiometry), anthropometry, serum leptin, insulin, cortisol, osteocalcin, C-terminal telopeptide of type I collagen (CTx) and total plasma proteins were measured in judoists at normal body weight, after weight reduction and after weight regain. Physical training, weight cycling history, menstrual status and nutritional intake using a 7-day food record were assessed. Results: Precompetitive weight loss averaged 4^0.3% of bodyweight and resulted in a significant decrease in leptin levels of 64% (P , 0.001) and of 31% for insulin (P , 0.0001). CTx and cortisol concentrations rose by 33% (P , 0.0001) and 81% (P , 0.05) respectively. Osteocalcin and total plasma protein remained unaffected by weight loss. A 4^0.5% weight regain induced a 276% increase in leptin levels (P , 0.001) and an 18% increase in insulin (P , 0.001). CTx and cortisol decreased by 23% (P , 0.0001) and 27% (P , 0.05) respectively. Changes in leptin were significantly correlated with changes in bone resorption marker in response to both weight loss (r ¼ 0.56, P , 0.01) and regain (r ¼ 0.44, P , 0.05). Conclusions: These findings suggest that leptin is involved in the regulation of bone metabolism in healthy adults and might play a potential role in the prevention of osteoporosis.European Journal of Endocrinology 154 389-395

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“…(9,10) Only a small number of relatively short-term prospective or cross-sectional observations of bone mass have been reported after treatment of CS in children. (11)(12)(13)(14) Whereas prospective changes in total body and visceral abdominal fat in CS have been described in adults after cure of endogenous CS, apart from our original twin study, these issues have not been evaluated in children. (3,15,16) Thus, the longterm effects of endogenous CS in children on bone and fat mass remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Effects of Child- and Adolescent-Onset Endogenous Cushing Syndrome on Bone Mass, Body Composition, and Growth: A 7-Year Prospective Study Into Young Adulthood

Leong

Abad

Charmandari

et al. 2007

Journal of Bone and Mineral Research

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The long-term effects on bone and fat mass in children with endogenous CS are unknown. In 14 children followed for 3-7 years into young adulthood after cure of CS, whereas bone mass largely recovered, persisting increases in total body and visceral fat suggests an increase risk of the metabolic syndrome.Introduction: Endogenous Cushing syndrome (CS) is associated with decreased bone mass and increased central fat mass. Whereas bone mass seems to improve after successful treatment, little is known about whether central fat persists. Materials and Methods:This was a prospective study of 14 children (10 girls and 4 boys) and adolescents with CS who were successfully treated and remained eucortisolemic. Growth, puberty, bone mass, and body composition were evaluated at baseline and during regular follow-up for 3 years and in seven children for a further 4 years of remission to assess final adult height (FH), BMI, bone mass, and body composition. Results: CS compromised growth, leading to about a −0.8 SD loss of FH and 0.9 SD increase in weight and BMI. BMD apparent density (BMAD) SD Score (SDS) at the lumbar spine (LS) at diagnosis were −1.8 and −1.25, respectively, and after 3 years of follow-up approached the mean with no further increase apparent up to 7 years of follow-up. Whereas hip BMD SDS increased from −1.3 at diagnosis to −0.40 at 3 years and 0 at 7 years of follow-up, femoral neck BMAD remained at or around 0 SDS at diagnosis and during follow-up. BMI was >25 kg/m 2 in five of seven adult subjects, most of whom were women. Total body fat and the ratio of visceral to subcutaneous was abnormally high in the majority of these subjects, whereas LS volumetric BMD was −0.7 SDS. Conclusions: Despite remission of CS, children and adolescents have significant alterations in body composition that result in a small but significant decrease in bone mass and increase in visceral adiposity. Although bone mass largely recovers after endogenous CS, changes in total and visceral fat suggest these subjects are at increased risk of the metabolic syndrome. Therefore, long-term monitoring of body fat and bone mass is mandatory after treatment of CS.

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Severe impairment of bone mass and turnover in Cushing’s disease: comparison between childhood‐onset and adulthood‐onset disease

Cited by 70 publications

References 41 publications

Body mass index and disease duration are predictors of disturbed bone turnover in anorexia nervosa. A case–control study

Body mass index and disease duration are predictors of disturbed bone turnover in anorexia nervosa. A case–control study

Relationships between serum leptin and bone markers during stable weight, weight reduction and weight regain in male and female judoists

Effects of Child- and Adolescent-Onset Endogenous Cushing Syndrome on Bone Mass, Body Composition, and Growth: A 7-Year Prospective Study Into Young Adulthood

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