Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome

Context: Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. Objective: The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. Results: Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both P < 0.01). The changes in BMD LS and TBS were not correlated (P = 0.87). The TBS change was found to be −4.5 % (±6.7; P = 0.003) in men and −0.3 % (±6.8; P = 0.85) in women (P = 0.063 for interaction men vs women). The mean BMD LS increased in men +4.2 g/cm 2 (±4.3; P < 0.001), but not in women +1.5 g/ cm 2 (±5.6; P = 0.36); (P = 0.073 for interaction). BMD increased in the ultradistal radius and total body (both P < 0.01).The increase in BMD LS was associated with a decrease in P1NP and CTX-1 (P < 0.001) and with lower P1NP and CTX-1 at the follow-up (P < 0.02). Conclusion: Treatment of acromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control.

Section: Bmd Measurementsmentioning

confidence: 99%

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Godang

Olarescu

Bollerslev

et al. 2016

“…CS patients display low levels of osteocalcin which in turn has been associated with impaired glucose metabolism, insulin resistance and visceral fat (VAT) (38,39). Thioredoxin interacting protein (TXNIP)-1 is upregulated in bone cells by GCs and might contribute to reduced osteocalcin levels.…”

Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

146

121

Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

“…Nine patients diagnosed with CS (12) were recruited based on clinical evaluation and biochemical workup (13,14). Biological specimens (blood, bone biopsies) were first collected at baseline (untreated), and then again 3G1.3 (meanGS.D.)…”

Section: Subjectsmentioning

confidence: 99%

“…BMD was measured by dual-energy X-ray absorptiometry (LUNAR Corp., Madison, WI, USA) (13). The values were expressed as Z-scores.…”

Section: Bmd Measurementmentioning

confidence: 99%

TXNIP is highly regulated in bone biopsies from patients with endogenous Cushing's syndrome and related to bone turnover

Lekva

Ueland²,

Bøyum³

et al. 2012

ObjectivePatients with endogenous Cushing's Syndrome (CS), as long-time treated patients with exogenous glucocorticoids (GCs), have severe systemic manifestations including secondary osteoporosis and low-energy fractures. The aim of the present study was to investigate the functional role ofTXNIPin bone with focus on osteoblast (OB) differentiation and OB-mediated osteoclast activity and functionin vitro.Design and methodsNine bone biopsies from CS before and after surgical treatment were screened for expressional candidate genes. Microarray analyses revealed that the gene encodingTXNIPranked among the most upregulated genes. Subsequentin vitroandin vivostudies were performed.ResultsWe found thatTXNIPgene in bone is downregulated in CS following surgical treatment. Furthermore, ourin vivodata indicate novel associations between thioredoxin andTXNIP. Ourin vitrostudies showed that silencingTXNIPin OBs was followed by increased differentiation and expression and secretion of osteocalcin as well as enhanced activity of alkaline phosphatase. Moreover, treating osteoclasts with silenced TXNIP OB media showed an increased osteoclast activity.ConclusionsTXNIPexpression in bone is highly regulated during the treatment of active CS, and by GC in bone cellsin vitro. Our data indicate that TXNIP may mediate some of the detrimental effects of GC on OB function as well as modulate OB-mediated osteoclastogenesis by regulating the OPG/RANKL ratio.