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

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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Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

Acta Endocrinologica ◽

10.1530/eje-14-0747 ◽

2015 ◽

Vol 172 (1) ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Oskar Ragnarsson ◽

Camilla A M Glad ◽

Ragnhildur Bergthorsdottir ◽

Erik G Almqvist ◽

Eva Ekerstad ◽

...

Keyword(s):

Bone Mineral Density ◽

Body Composition ◽

Bone Mineral ◽

Fat Mass ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Abdominal Fat ◽

Controlled Study ◽

Mineral Density

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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Long-term consequences of fracture of the lower leg: cross-sectional study and long-term longitudinal follow-up of bone mineral density in the hip after fracture of lower leg

Bone ◽

10.1016/s8756-3282(98)00153-7 ◽

1999 ◽

Vol 24 (2) ◽

pp. 131-134 ◽

Cited By ~ 34

Author(s):

E van der Poest Clement ◽

H van der Wiel ◽

P Patka ◽

J.C Roos ◽

P Lips

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Lower Leg ◽

Cross Sectional Study ◽

Sectional Study ◽

Mineral Density ◽

Cross Sectional ◽

Long Term Consequences

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Bone histomorphometry, bone mineral density at multiple skeletal sites, and biochemical markers in a three year follow-up study of surgical treated patients with primary hyperparathyroidism.

Bone ◽

10.1016/8756-3282(96)89387-2 ◽

1996 ◽

Vol 19 (3) ◽

pp. 162S

Author(s):

T STEINICHE

Keyword(s):

Bone Mineral Density ◽

Primary Hyperparathyroidism ◽

Bone Mineral ◽

Biochemical Markers ◽

Bone Histomorphometry ◽

Mineral Density ◽

Follow Up Study

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Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas

Acta Endocrinologica ◽

10.1530/eje-09-0957 ◽

2010 ◽

Vol 162 (4) ◽

pp. 779-785 ◽

Cited By ~ 45

Author(s):

R Giordano ◽

E Marinazzo ◽

R Berardelli ◽

A Picu ◽

M Maccario ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cumulative Risk ◽

Cushing's Syndrome ◽

Endocrine Function ◽

Adrenal Incidentalomas ◽

Term Outcome ◽

Long Term Outcome ◽

Significant Clinical Improvement

ObjectiveTo evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas.Design and methodsA total of 118 patients (77 F and 47 M; age 62.3±1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1–10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery.ResultsAt entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%,P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic–cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement.ConclusionsThe risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.

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Long-term follow up after denosumab treatment for osteoporosis – rebound associated with hypercalcemia, parathyroid hyperplasia, severe bone mineral density loss, and multiple fractures: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02401-0 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Yves Maugars ◽

Pascale Guillot ◽

Joëlle Glémarec ◽

Jean-Marie Berthelot ◽

Benoit Le Goff ◽

...

Keyword(s):

Bone Mineral Density ◽

Case Report ◽

Bone Mineral ◽

Mineral Density ◽

Multiple Fractures ◽

Bone Mineral Density Loss ◽

Long Term Follow Up ◽

Denosumab Treatment

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Trajectories of Bone Remodeling Markers and Bone Mineral Density during Treatment with Strontium Ranelate in Postmenopausal Women Previously Treated with Bisphosphonates

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.4137/cmed.s15086 ◽

2014 ◽

Vol 7 ◽

pp. CMED.S15086 ◽

Cited By ~ 3

Author(s):

Helisane Lima ◽

Juliana Maia ◽

Francisco Bandeira

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Postmenopausal Women ◽

Bone Mineral ◽

Strontium Ranelate ◽

Mineral Density ◽

Bone Remodeling Markers ◽

Before And After ◽

Previously Treated

Objective To evaluate the responses of C-terminal telopeptide (CTX) and serum osteocalcin after the first 4 months of treatment with strontium ranelate (SR) and demonstrate their association with long-term bone density changes. Subjects and Methods A sample of 13 postmenopausal women with osteoporosis was analyzed (mean age 65 ± 7.7 years), who were treated with SR for an average of 2.56 ± 0.86 years. All patients had undergone previous treatment with bisphosphonates for an average period of 4.88 ± 2.27 years. Serum CTX and osteocalcin levels were determined before and after four months of treatment with SR. Bone mineral density in the lumbar spine and femoral neck were obtained before and after treatment with SR. Results We observed an average increase of 53.7% in the CTX levels, and 30.7% in the osteocalcin levels. The increase in bone markers was associated with a mean 4.8% increase in lumbar spine bone mineral density (BMD) from 0.820 to 0.860 g/cm2 ( T-score from –2.67 to –1.92; P= 0.001), after 2.5 years of treatment with SR. Conclusion These data suggest an anabolic effect of SR on postmenopausal women who were previously treated with long-term bisphosphonates.

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