Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing’s disease

Guo, Weihong; Li, Fengao; Zhu, Chonggui; Wang, Baoping; Wang, Kunling; Dai, Chenlin; Jia, Hongwei; H, Wei; He, Qing; Cui, Jin; Yuan, Menghua; Tang, Shao-hui; Liu, Wei; Zhu, Tiehong; Gao, Zhihong; Zheng, Fangqiu; Ma, Zhenzhen; Qu, Hui‐Qi; Zhu, Mei

doi:10.1177/0300060517725660

Cited by 26 publications

(29 citation statements)

References 18 publications

(23 reference statements)

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“…These effects may be protective against osteonecrosis [ 5 , 8 , 9 ]. The potential positive effects of ACTH-induced VEGF release on bone are clinically evident in patients with ACTH-producing pituitary Cushing disease; these patients have less BMD loss than those with adrenal Cushing syndrome (with suppressed ACTH levels) [ 21 , 22 ]. In addition, ACTH concentrations in patients with pituitary Cushing disease correlate with lumbar BMD [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…The potential positive effects of ACTH-induced VEGF release on bone are clinically evident in patients with ACTH-producing pituitary Cushing disease; these patients have less BMD loss than those with adrenal Cushing syndrome (with suppressed ACTH levels) [ 21 , 22 ]. In addition, ACTH concentrations in patients with pituitary Cushing disease correlate with lumbar BMD [ 22 ]. Moreover, due to feedback on the hypothalamic-pituitary-adrenal axis, patients with familial glucocorticoid deficiency with elevated ACTH levels have a higher BMD than age-matched controls [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Novel function of adrenocorticotropic hormone in the stimulation of vascular endothelial growth factor release in healthy children and adolescents: a proof-of-concept study

Heksch

Bowden

Hoffman

2021

Ann Pediatr Endocrinol Metab

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Purpose To assess the effect of adrenocorticotropic hormone (ACTH) on plasma vascular endothelial growth factor (VEGF) levels in healthy children and adolescents and to inform future work on the effects of ACTH on VEGF in bone. Methods An Institutional Review Board-approved prospective study of 10 healthy subjects, ages 9–17, was conducted to assess the effect of ACTH on plasma VEGF levels. VEGF levels were collected at baseline and every 30 minutes for 3 hours. Cosyntropin (a synthetic ACTH analogue) was administered at a low-dose (1 μg) given at t=0 minutes and a high-dose (250 μg) given at t=60 minutes. A Friedman test was performed comparing baseline to peak VEGF levels after stimulation with low-dose and high-dose cosyntropin. Results Peak plasma VEGF levels significantly increased after high-dose cosyntropin compared with baseline ( P =0.042). Peak plasma VEGF levels did not significantly increase after low-dose cosyntropin compared to baseline. Conclusions To our knowledge, this is the first study to demonstrate that ACTH administration causes a significant increase in plasma VEGF levels in humans. This finding may have important implications in the protective effects of ACTH on bone. Decreased bone mineral density and adrenal suppression are common side effects of glucocorticoid use in pediatrics. VEGF increases vascularity and may play a role in reducing glucocorticoid-induced bone disease. Animal studies have shown that ACTH stimulates release of VEGF in osteoblasts, though this effect has yet to be evaluated in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Novel function of adrenocorticotropic hormone in the stimulation of vascular endothelial growth factor release in healthy children and adolescents: a proof-of-concept study

Heksch

Bowden

Hoffman

2021

Ann Pediatr Endocrinol Metab

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“…P1NP and procollagen carboxy‐terminal propeptide (P1CP) have also been studied in several studies, with contradictory results . In a retrospective study with 21 patients with CS, it was shown that osteocalcin is depressed; this applies also for PINP, whereas CTX is increased …”

Section: Discussionmentioning

confidence: 99%

The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2-Year Follow-Up Study

Braun

Fazel

Zopp

et al. 2020

Journal of Bone and Mineral Research

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Endogenous Cushing's syndrome (CS) is a rare cause of secondary osteoporosis. The long‐term consequences for bone metabolism after successful surgical treatment remain largely unknown. We assessed bone mineral density and fracture rates in 89 patients with confirmed Cushing's syndrome at the time of diagnosis and 2 years after successful tumor resection. We determined five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. The bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide (PINP), alkaline bone phosphatase, CTX‐I, and TrAcP 5b were measured in plasma or serum by chemiluminescent immunoassays. For comparison, 71 sex‐, age‐, and body mass index (BMI)‐matched patients in whom Cushing's syndrome had been excluded were studied. None of the patients received specific osteoanabolic treatment. At time of diagnosis, 69% of the patients had low bone mass (mean T‐score = −1.4 ± 1.1). Two years after successful surgery, the T‐score had improved in 78% of patients (mean T‐score 2 years postoperatively −1.0 ± 0.9). The bone formation markers osteocalcin and intact PINP were significantly decreased at time of diagnosis (p ≤ 0.001 and p = 0.03, respectively), and the bone resorption marker CTX‐I and TrAcP 5b increased. Postoperatively, the bone formation markers showed a three‐ to fourfold increase 1 year postoperatively, with a moderate decline thereafter. The bone resorption markers showed a similar but less pronounced course. This study shows that the phase immediately after surgical remission from endogenous CS is characterized by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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“…Long-term exposure to excess GCs in patients with hypercortisolism results in bone loss. According to the recent study, ACTH might be protective for lumbar bone mineral density in patients with Cushing's disease, indicating ACTH might have a protective effect on bone ( Guo et al, 2018 ). Moreover, familial glucocorticoid deficiency (FGD), or hereditary unresponsiveness to ACTH, is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex ( Maharaj et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Bone phenotype in melanocortin 2 receptor-deficient mice

et al. 2020

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Considering that stress condition associated with osteoporosis, the hypothalamic-pituitary-adrenal (HPA) axis, which is essential for central stress response system, is implicated in regulating bone mass accrual. Melanocortin 2 receptor (MC2R), the receptor of adrenocorticotropic hormone is expressed in both adrenal gland cells and bone cells. To elucidate the role of HPA axis in bone metabolism, we assessed the skeletal phenotype of MC2R deficient mice ( MC2R −/− mice). We first examined bone mineral density and cortical thickness of femur using dual x-ray absorptiometry and micro-computed tomography. We then conducted histomorphometric analysis to calculate the static and dynamic parameters of vertebrae in MC2R −/− mice. The levels of osteoblastic marker genes were examined by quantitative PCR in primary osteoblasts derived from MC2R −/− mice. Based on these observations, bone mineral density of femur in MC2R −/− mice was increasing relative to litter controls. Meanwhile, the thickness of cortical bone of femur in MC2R −/− mice was remarkably elevated. Moreover, serum osteocalcin level was drastically raised in MC2R −/− mice. However, bone histomorphometry revealed that static and dynamic parameters reflecting bone formation and resorption were unchanged in vertebrae of MC2R −/− mice compared to the control, indicating that MC2R function may be specific to appendicular bone than axis bone. Taken together, the HPA axis due to deletion of MC2R is involved in bone metabolism.

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Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing’s disease

Cited by 26 publications

References 18 publications

Novel function of adrenocorticotropic hormone in the stimulation of vascular endothelial growth factor release in healthy children and adolescents: a proof-of-concept study

Novel function of adrenocorticotropic hormone in the stimulation of vascular endothelial growth factor release in healthy children and adolescents: a proof-of-concept study

The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2-Year Follow-Up Study

Bone phenotype in melanocortin 2 receptor-deficient mice

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