Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome.

ObjectiveAdverse body compositional features and low bone mineral density (BMD) are the characteristic of patients with active Cushing's syndrome (CS). The aim of this study was to evaluate body composition and BMD in women with CS in long-term remission and the influence of polymorphisms in genes affecting glucocorticoid (GC) sensitivity on these end-points.Design, patients and methodsThis was a cross-sectional, case–controlled study, including 50 women previously treated for CS and 50 age and gender-matched controls. Median (interquartile range) remission time was 13 (5–19) years. Body composition and BMD were measured with dual-energy X-ray absorptiometry. Five polymorphisms in four genes associated with GC sensitivity were analysed using TaqMan or Sequenom single-nucleotide polymorphism genotyping.ResultsPatients with CS in remission had increased abdominal fat mass (P<0.01), whereas BMD was not significantly different at any site between patients and controls. In patients, the NR3C1 Bcl1 polymorphism was associated with reduced total (P<0.05) and femur neck BMD (P<0.05). The polymorphism rs1045642 in the ABCB1 gene was associated with increased abdominal fat mass (P<0.05) and decreased appendicular skeletal muscle mass (P<0.05). GC replacement was associated with reduced total BMD (P<0.01), BMD at lumbar spine (P<0.05) and increased abdominal fat (P<0.01).ConclusionOngoing GC replacement therapy together with polymorphisms in two genes related with GC sensitivity is associated with abdominal obesity and adverse skeletal health in patients with CS in long-term remission.

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Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: A prospective, long-term study

Acta Endocrinologica ◽

10.1530/eje.1.02067 ◽

2006 ◽

Vol 154 (1) ◽

pp. 109-118 ◽

Cited By ~ 82

Author(s):

Cybèle Kristo ◽

Rune Jemtland ◽

Thor Ueland ◽

Kristin Godang ◽

Jens Bollerslev

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Bone Mineral ◽

Cushing’S Syndrome ◽

Biochemical Markers ◽

Cushing's Syndrome ◽

Mineral Density ◽

Long Term Outcome

Objective: Endogenous Cushing’s syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. Design: We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. Methods: Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). Results: Mann–Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman’s rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson’s correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. Conclusion: Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).

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Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing's syndrome

Clinical Endocrinology ◽

10.1111/j.1365-2265.2004.01968.x ◽

2004 ◽

Vol 60 (2) ◽

pp. 264-270 ◽

Cited By ~ 19

Author(s):

N. Karavitaki ◽

G. Ioannidis ◽

F. Giannakopoulos ◽

P. Mavrokefalos ◽

N. Thalassinos

Keyword(s):

Bone Mineral Density ◽

Postmenopausal Women ◽

Bone Mineral ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Newly Diagnosed ◽

Mineral Density ◽

Peripheral Skeleton

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Trabecular bone score as one of the new methods of non-invasive evaluation of bone microarchitecture in patients with Cushing’s syndrome

Problems of Endocrinology ◽

10.14341/probl20156149-16 ◽

2015 ◽

Vol 61 (4) ◽

pp. 9-16

Author(s):

N V Dragunova ◽

Z E Belaya ◽

N I Sasonova ◽

A G Sopodovnikov ◽

T T Tsoriev ◽

...

Keyword(s):

Bone Mineral Density ◽

Trabecular Bone ◽

Bone Mineral ◽

Cushing’S Syndrome ◽

Vertebral Fractures ◽

Trabecular Bone Score ◽

Bone Microarchitecture ◽

Cushing's Syndrome ◽

Z Score ◽

Mineral Density

Objective - to evaluate the value of trabecular bone score and risk factors of fractures in patients with Cushing’s syndrome (CS). Material and methods. One hundred eighty two patients with laboratory-confirmed Cushing’s syndrome were enrolled. All patients underwent measurement of bone mineral density (BMD) at the lumbar spine (LI-LIV), femoral neck and total hip using DXA Prodigy (GEHC Lunar, Madison, WI, USA). Trabecular bone score (TBS) was assessed retrospectively on the basis of already existing DXA images using software TBS iNsight software v2.1 (Medimaps, Merignac, France). Each patient was interviewed for the presence of low-traumatic fractures during the active stage of the disease. A lateral X-ray of the thoracic and lumbar spine ThIV-LV was performed to estimate vertebral fractures. Twenty-four hours urinary free cortisol (24hUFC) was measured by imunochemiluminescence assay VITROS ECi with the preliminary extraction with diethyl ether (reference values 60-413 nmol/24 h). Results. Among 182 patients with CS (149 women, 33 men), Cushing’s disease was confirmed in 151 cases, 9 patients diagnosed with benign adrenal tumor and 22 - ACTH-ectopic syndrome. The median of age - 35 (Q25-Q75 27-49) years, body mass index - 29 (26-33) kg/m2, 24hUFC - 1760 (985-2971) nmol/24h. Fractures were confirmed in 80 (44%) cases, 70 patients suffered from vertebral fractures, which were multiple in 53 cases; 23 patients had non-vertebral fractures. Median of trabecular bone score was 1.205 (1.102-1.307), which is much lower than expected in healthy volunteers (>1.350), while the decrease in bone mineral density (BMD) did not correspond to the severity and prevalence of osteoporosis fractures: LI-LIV Z-score - 1.7 (2.5-0.73); femoral neck Z-score - 1 (-1.6- -0.4). However, when using binary logistic regression analysis (adjusted for sex, age, body mass index, bone mineral density, trabecular bone score and 24hUFC) revealed that the most significant predictor of fracture is high levels of 24hUFC (p=0.001) . The high prevalence of vertebral fractures in patients with CS most likely influenced the results of trabecular bone score and its ability to predict fractures. Conclusion. Patients with active CS have low trabecular bone score, rather than bone mineral density, which reflects deterioration in bone microarchitecture. The low-traumatic fracture occurrence depends on the severity of CS reflected in 24hUFC levels.

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