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INTRODUCTION: Bilateral neck exploration (BNE) has been the gold standard for the treatment of primary hyperparathyroidism (PHPT). Minimally invasive parathyroidectomy (MIP) has emerged as an alternative procedure for localised solitary adenomas. The most popular MIP techniques are the open MIP (OMIP) and the minimally invasive video-assisted parathyroidectomy (MIVAP). This study aims to assess whether we achieved a smooth transition from OMIP to MIVAP without compromising the results or increasing the cost. METHODS: A parathyroid adenoma was successfully localised preoperatively in 77/86 patients with PHPT. MIP was contraindicated in 27/86 cases. For MIVAP, a 5mm, 30 degree camera was employed, along with special instruments. RESULTS: Median preoperative parathyroid hormone (PTH) level was 145.9pg/dl (59-2,151) and median calcium (Ca) was 10.8mg/dl (9.3-19). Comparing MIVAP (N=31) with OMIP (N=28), there was no significant difference in the age, sex, location of the adenoma, preoperative PTH and Ca levels as well as in all the other factors compared, apart from the size of adenomas, which were bigger in the OMIP group (1.85cm vs 1.4cm, p=0.032). Moreover, cure rates, operating time, hospital stay and rates of postoperative normocalcaemia were similar between the two groups. CONCLUSIONS: Despite the learning curve, MIVAP was not found to be inferior to OMIP for localised adenomas. The final cost was no higher for MIVAP than OMIP with the use of common reusable instruments. This, along with surgeons' experience in parathyroid and endoscopic surgery facilitates a smooth and cost-effective transition from OMIP to MIVAP.

The original version of this article unfortunately contained a mistake in Fig. 1. The corrected Fig. 1 is given below. © 2021, The Author(s).

Background: Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. Methods: We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland–Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. Results: We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. Conclusion: Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed. © 2021, The Author(s).

Rebound-associated vertebral fractures (RAVFs) could occur in a minority of the patients who discontinue denosumab. In such patients, denosumab is often reinstituted to rapidly suppress bone turnover and avert the risk of additional fractures. Herein we report the cases of 2 patients who sustained RAVFs, and in whom resuming denosumab treatment did not avert the occurrence of new RAVFs a few months later, despite the suppression of bone turnover markers. It seems that denosumab reinstitution cannot completely eliminate the risk of new RAVFs and that the rebound of bone turnover may not be the sole mechanism to explain this phenomenon. © 2020 The International Society for Clinical Densitometry

Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections. © 2020, Hellenic Endocrine Society.

Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and

The affiliation details for Geltrude Mingrone are corrected below.

Background/Aim: Postsurgical hypoparathyroidism (PostHypo) is a common complication after total thyroidectomy. We studied the risk factors associated with PostHypo. Patients and Methods: The study included 109 women, (mean age: 50.7±10.75 years), who underwent total thyroidectomy for thyroid diseases. Results: Based on the development of biochemical hypocalcemia on the first postoperative day following total thyroidectomy, (cCa

Derangements in phosphate and calcium homeostasis are common in patients with beta-thalassemia. Fibroblast growth factor 23 (FGF23) is among the main hormones regulating phosphate levels, while several studies underline an interplay between iron (Fe) and FGF23. Herein, we investigated, for the first time, the serum intact molecule (iFGF23) and the carboxyl-terminal fragment (C-FGF23) and Klotho levels simultaneously in patients with beta-thalassemia major receiving iron chelation regimens in comparison to healthy control subjects. We also correlated them with the body iron burden. The observational case-control study included 81 subjects (40 thalassemic patients and 41 healthy controls). Serum iFGF23, C-FGF23 and Κlotho were measured by ELISA. Parathormone, 25-hydroxycholecalciferol, calcium, and phosphorus were measured in blood and/or urine. The degree of hemosiderosis was evaluated by assessing the serum ferritin levels and performing T2∗ MRI measurements. Serum C-FGF23 levels were significantly lower in patients compared to control subjects (p=0.04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=-0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in βTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients. © 2020 BMJ Publishing Group. All rights reserved.

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders characterized by parathyroid hormone (PTH)-dependent hypercalcemia. Cardinal features include low trauma fractures, nephrolithiasis, and chronic kidney disease. Several experimental studies established that parathyroid hormone exerts actions on the cardiovascular (CV) system, including vasodilatation and positive inotropic and chronotropic effects. Observational studies, especially in severe cases, report a higher prevalence of hypertension, diabetes mellitus, lipid abnormalities, endothelial dysfunction, arrhythmias, and left ventricular hypertrophy in patients with PHPT, while the risk of CV events seems to be increased in severe cases. However, the effect of surgery is inconsistent on CV abnormalities and, more importantly, on CV disease (CVD) events, especially in mild cases. In the current review, we describe the available evidence linking PHPT and CVD, as well as the effect of surgical management and pharmacological treatment on CVD manifestations in patients with PHPT. Based on the current evidence, CVD is not considered an indication for surgery. © 2020 Bentham Science Publishers.

The Bone Section of the Hellenic Endocrine Society has issued the recommendations herein presented with the aim of providing guidance on optimal management of patients with parathyroid disorders in everyday clinical practice within the Greek health care setting. Although the methodology followed to formulate these recommendations was not strictly based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles, they were drawn up after an extensive review of the literature and of the currently available guidelines for the management of parathyroid disorders worldwide. Specifically for primary hyperparathyroidism (PHPT), the 2011 guidelines of the Greek National Organization of Medicines were updated accordingly. In particular, definitions, etiologies, and recommended and optional laboratory and imaging examinations are provided both for PHPT and chronic hypoparathyroidism (HypoPT). Finally, treatment algorithms are provided for the management of both PHPT and HypoPT. Specifically for HypoPT, the treatment algorithm describes the recommended steps that should be followed to achieve optimal management of chronic hypocalcemia and the complications of HypoPT through the conventional treatment available in Greece and the use of recombinant human PTH(1-84). © 2020, Hellenic Endocrine Society.

Summary: We report the updated guidelines for the management of osteoporosis in Greece, which include guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information, and national evidence from Greek clinical practice and the healthcare setting. Purpose: The purpose of this report was to update the Guidelines for the Management of Osteoporosis in Greece that was published in 2011. Methods: In line with the GRADE system, the working group initially defined the main clinical questions that should be addressed when dealing with the diagnosis and management of osteoporosis in clinical practice in Greece. Following a literature review and discussion on the experience gained from the implementation of the 2011 Guidelines transmitted through the national electronic prescription network, the Hellenic Society for the Study of Bone Metabolism (HSSBM) uploaded an initial draft for an open dialogue with the relevant registered medical societies and associations on the electronic platform of the Greek Ministry of Health. After revisions, the Central Health Council approved the final document. Results: The 2018 Guidelines provide comprehensive recommendations on the issues of the timing of fracture risk evaluation and dual-energy X-ray absorptiometry (DXA) measurement, interpretation of the DXA results, the diagnostic work-up for osteoporosis, the timing as well as the suggested medications for osteoporosis treatment, and the follow-up methodology employed during osteoporosis treatment. Conclusions: These updated guidelines were designed to offer valid guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information and national evidence from clinical practice and the healthcare setting. Clinical judgment is essential in the management of every individual patient for the purpose of achieving the optimal outcome in the safest possible way. © 2019, International Osteoporosis Foundation and National Osteoporosis Foundation.

Denosumab (Dmab), a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) which substantially suppresses osteoclast activity, has been approved for the treatment of common metabolic bone diseases, including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis, in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated. However, the imbalance of RANKL/RANK/osteoprotegerin is also implicated in the pathogenesis of several other rare metabolic bone diseases, including Juvenile Paget disease, fibrous dysplasia, Hajdu Cheney syndrome and Langerhans cell histiocytosis, thus rendering Dmab a potential treatment option for these diseases. Dmab has been also administered off-label in selected patients (e.g., with Paget's disease, osteogenesis imperfecta, aneurysmal bone cysts) due to contraindications or unresponsiveness to standard treatment, such as bisphosphonates. Moreover, Dmab was administered to improve hypercalcemia induced by various diseases, including primary hyperparathyroidism, tuberculosis and immobilization. The aim of this review is to summarize existing evidence on off-label uses of Dmab in metabolic bone diseases and provide opinion for or against its use, which should be always considered on an individual basis. © 2019 Elsevier Inc.

Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals. © 2019 Walter de Gruyter GmbH, Berlin/Boston.

Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or ‘lipokine’) to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic–euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = −0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.

Tertiary hyperparathyroidism (THP) is a rare complication in patients with hypophosphataemic rickets (HR), usually related to long-term management with active vitamin D analogues and oral phosphate salts. If left untreated, THP may aggravate bone and renal disease. We report a case of THP, which developed during the course of HR. Preoperatively, cinacalcet administration along with gradual increase in alphacalcidol dose, led to almost normalization of serum calcium and decrease in parathyroid hormone (PTH) concentrations. The patient underwent an uneventful subtotal parathyroidectomy, resulting in PTH normalization and stabilization of eucalcaemia during 18 months of follow-up. We conclude that, except for optimal dosage of elementary phosphate and alphacalcidol, cinacalcet prior to parathyroidectomy may be an effective option in patients with HR complicated with THP. © 2019, International Society of Musculoskeletal and Neuronal Interactions. All rights reserved.

Summary: Vitamin D deficiency and quantitative ultrasound measurements are associated with bone fragility. We assessed these parameters and their correlates. 87.7% of the population has vitamin D inadequacy and this correlated with lifestyle factors. These results contribute to epidemiological data needed for population guidelines for bone health. Purpose: Vitamin D deficiency and quantitative ultrasound (QUS) parameters are among the most important clinical risk factors of bone fragility. Few data are available for Greek population. The aim of the study was to evaluate the serum 25-hydroxyvitamin D [25(OH)D] level and their determinants, as well as QUS parameters in Greek population. Methods: OSTEOS is an observational cross-sectional study conducted from June 2010 to July 2012. Nine hundred seventy adults were recruited from rural and urban areas throughout Greece and completed the appropriate questionnaire. Serum 25(OH)D measured by enzyme immunoassay, QUS parameters, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), was assessed with an Achilles device. Univariate Analysis of Variance was used for the assessment of serum 25(OH)D determinants. Results: Mean serum 25(OH)D of the total population was 20,00 ± 8,00 ng/mL. Females had lower levels than males. The negative determinants of serum 25(OH)D in the total population were the female sex and the winter-spring season of sampling while age proved negative association solely in obese subjects. Positive determinants of vitamin D status were summer sun exposure and organized physical activity as expected. Urban had lower SOS and SI than rural residents. Individuals with 25(OH)D ≥ 20 ng/mL had higher SOS than those with 25(OH)D < 20 ng/mL. BUA, SOS, and SI are positively correlated with organized physical activity and negatively with PTH. Conclusions: This study reports that vitamin D deficiency is highly prevalent among healthy Greek men and women, demonstrates the multifactorial causation of 25(OH)D levels, and points out that further research is required to determine more factors related to vitamin D status and bone health. © 2018, International Osteoporosis Foundation and National Osteoporosis Foundation.

Osteogenesis imperfecta (OI) is the most common inherited form of bone fragility and includes a heterogenous group of genetic disorders which most commonly result from defects associated with type 1 collagen. 85%–90% of cases are inherited in an autosomal dominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects in type 1 collagen. In the last decade, defects in several other proteins involved in the normal processing of type 1 collagen have been described. Recent advances in genetics have called for reconsideration of the classification of OI, however, most recent classifications align with the classic clinical classification by Sillence. The hallmark of the disease is bone fragility but other tissues are also affected. Intravenous bisphosphonates (BPs) are the most widely used intervention, having significant favorable effects regarding areal bone mineral density (BMD) and vertebral reshaping following fractures in growing children. BPs have a modest effect in long bone fracture incidence, their effects in adults with OI concerns only BMD, while there are reports of subtrochanteric fractures resembling atypical femoral fractures. Other therapies showing promising results include denosumab, teriparatide, sclerostin inhibition, combination therapy with antiresorptive and anabolic drugs and TGF-β inhibition. Gene targeting approaches are under evaluation. More research is needed to delineate the best therapeutic approach in this heterogeneous disease. © 2017 Elsevier Inc.

Context: Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment. Objective: To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum. Design: Observational, open label, nonrandomized clinical trial. Setting: The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece. Patients and Interventions: Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months. Main Outcome Measures: Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months. Results: We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment. Conclusions: Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133). Copyright © 2018 Endocrine Society.

Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by brittle bones and extraskeletal manifestations. The disease phenotype varies greatly. Most commonly, OI arises from monoallelic mutations in one of the two genes encoding type I collagen, COL1A1 and COL1A2 and is inherited as an autosomal dominant trait. Here, we describe a consanguineous family with autosomal recessive OI caused by a novel homozygous glycine substitution in COL1A2, NM_000089.3: c.604G>A, p.(Gly202Ser), detected by whole-genome sequencing. The index patient is a 31-year-old Greek woman with severe skeletal fragility. She had mild short stature, low bone mineral density of the lumbar spine and blue sclerae. She had sustained multiple long bone and vertebral fractures since childhood and had been treated with bisphosphonates for several years. She also had an affected sister with similar clinical manifestations. Interestingly, the parents and one sister, all carriers of the COL1A2 glycine mutation, did not have manifestations of OI. In summary, we report on autosomal recessive OI caused by a homozygous glycine-to-serine substitution in COL1A2, leading to severe skeletal fragility. The mutation carriers lacked OI manifestations. This family further expands the complex genetic spectrum of OI and underscores the importance of genetic evaluation for correct genetic counselling. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

This study investigated the effects of different levels of habitual physical activity (PA) assessed by pedometry on bone turnover markers of preadolescent girls according to a cross-sectional experimental design. Sixty prepubertal girls of similar chronological age, bone age, maturity level, and nutritional status were assigned to a low PA (LPA; n = 25), a moderate PA (MPA; n = 17), or a high PA (HPA; n = 18) group. Dual-energy X-ray absorptiometry was used to measure areal bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine (L2–L4) and dominant hip (femoral neck and trochanter). Blood was collected for the measurement of alkaline phosphatase (ALP), bone-specific ALP (BSAP), procollagen type I N-terminal propeptide (PINP), C-terminal telopeptide of collagen I (CTX), parathyroid hormone (PTH), osteocalcin, thyroid-stimulating hormone, estradiol, testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. ANOVA revealed that the HPA group (18,695 ± 1244 steps per day) had a lower daily energy intake and body mass than the MPA group (10,774 ± 521 steps per day) and the LPA group (7633 ± 1099 steps per day). The HPA group had higher (P

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p < 0.001, respectively) independently of age; BMD; duration of dialysis; and serum levels of alkaline phosphatase, 25-OH-vitamin D, parathyroid hormone, fetuin-A, or plasma FGF-23. Patients on HD who were diagnosed with an osteoporotic vertebral fracture had numerically lower TBS values, albeit without reaching statistical significance, compared with patients on dialysis without a fracture (1.044 ± 0.151 vs 1.124 ± 0.173, respectively, p = 0.079). Bone microarchitecture, as assessed by TBS, is significantly altered in ESRD on patients on HD independently of BMD values and metabolic changes that reflect chronic kidney disease-mineral and bone disorder. © 2016 International Society for Clinical Densitometry

Polyostotic fibrous dysplasia in combination with caféau- lait macules and hyperfunctioning endocrinopathies consists of a rare clinical condition termed as McCune- Albright syndrome. Aneurysmal bone cysts are tumorlike cystic lesions, composed of blood-filled compartments. They may occur as primary lesions or secondary to other pathologies; most commonly giant cell tumors of bone. However, secondary aneurysmal bone cysts in McCune-Albright syndrome are exceptional. We present a 28-year-old female with McCune-Albright syndrome. She experienced precocious puberty at age 3 months. In childhood, she experienced multiple long bone fractures, facial deformity and progressive visual and hearing impairment. One year ago, she experienced a painful, gradually enlarging bone lesion involving the right ilium, pubic and ischial bone with groundglass appearance, septa, marginal sclerosis, endosteal scalloping and blow-out expansion resulting in localized thinning of the cortex. CT-guided needle biopsy of the pelvic lesion showed aneurysmal bone cyst. Selective arterial embolization was recommended, however, the patient and her relatives did not consent to proceed to treatment, and she remained in close surveillance thereafter.

Objective— Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. Approach and Results— We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher ( P P Conclusions— In young-to-middle aged apparently healthy people, the association of CCA-IMT with insulin sensitivity and its metabolic correlates differs between men and women. Lower insulin sensitivity is associated with higher IMT only in men; this association seems to be mediated by circulating free fatty acids and adipocytokines. In women, CCA-IMT is independently associated with fasting plasma glucose.

ObjectiveFasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis.Design and methodsThe Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30–60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis.ResultsFasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8–10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6–9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3–4.7, adjusted for fasting insulin) in men and 1.6 (0.8–3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women.ConclusionsFasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.

Udgivelsesdato: 2009-May Patients with fatty liver (FL) disease have a high risk of developing diabetes and cardiovascular diseases. The aim was to evaluate the association between FL, insulin resistance (IR), coronary heart disease (CHD) risk, and early atherosclerosis in a large European population (RISC Study). In 1,307 nondiabetic subjects (age 30-60 years) recruited at 19 centers, we evaluated liver enzymes, lipids, insulin sensitivity (by euglycemic-hyperinsulinemic clamp), glucose tolerance (by 75 g oral glucose tolerance test), carotid atherosclerosis as intima media thickness (IMT), CHD risk by the Framingham Heart study prediction score, and physical activity (by accelerometer). The presence of FL was estimated using the fatty liver index (FLI; >60, likelihood >78% presence FL; FLI 91% absence of FL). Subjects were divided into three groups: G1: FLI 60 (n = 234), G2: intermediate group (n = 465). Compared to G1, G3 included more men (70% versus 24%) and people with impaired glucose tolerance (23% versus 5%). IMT increased with FLI (G3 = 0.64 +/- 0.08 versus G1 = 0.58 +/- 0.08 mm, P < 0.0001). FLI was associated with increased CHD risk (r = 0.48), low-density lipoprotein cholesterol (r = 0.33), alanine aminotransferase (r = 0.48), aspartate aminotransferase (r = 0.25), systolic blood pressure (r = 0.39) and IMT (r = 0.30), and reduced insulin sensitivity (r = -0.43), high-density lipoprotein cholesterol (r = -0.50), adiponectin (r = -0.42), and physical activity (r = -0.16, all P < 0.0001). The correlations hold also in multivariate analysis after adjusting for age, gender, and recruiting center. Conclusion: In middle-age nondiabetic subjects, increased IMT, CHD risk, and reduced insulin sensitivity are associated with high values of FLI.

Studies in postmenopausal women have identified sclerostin as a strong candidate for mediating estrogen effects on the skeleton. The effects of estradiol on sclerostin and Dickkopf-1 in younger women remain unclear. The main purpose of this study is to investigate the impact of estradiol and gonadotrophins fluctuations during the menstrual cycle on circulating sclerostin and Dickkopf-1 levels and the possible relationship of sclerostin and Dickkopf-1 with changes in N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links. Fourteen healthy premenopausal Caucasian women, with regular menses, aged 33.6 ± 4.5 years participated. After the first day of menstruation and every-other-day up to the next menses, fasting serum estradiol, luteinizing hormone, follicle-stimulating hormone, sclerostin, Dickkopf-1, N-terminal propeptide of type 1 collagen, and C-telopeptide of collagen cross-links levels were measured in peripheral blood. Participants completed dietary questionnaires and the International physical activity questionnaire during the cycle. Neither sclerostin nor Dickkopf-1 levels changed significantly across the menstrual cycle (p = 0.18 and p = 0.39, respectively), while N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links levels presented cyclic variation (p < 0.001 and p = 0.004, respectively). Baseline sclerostin (29.23 ± 10.62 pmol/L) positively correlated with N-terminal propeptide of type 1 collagen (r = 0.71, p < 0.01) and C-telopeptide of collagen cross-links (r = 0.63, p < 0.05), while Dickkopf-1 (4.82 ± 2.23 pmol/L) correlated positively with N-terminal propeptide of type 1 collagen (r = 0.56, p < 0.05). Mid-cycle E2 levels presented significant negative association with the percent decrease of C-telopeptide of collagen cross-links at all-time points during the luteal period (r = −0.60 to −0.68, p < 0.05–0.01). Circulating sclerostin and Dickkopf-1 levels do not change across the menstrual cycle and do not demonstrate any relationship with estradiol in premenopausal women. Further investigation is needed concerning the role of sclerostin and Dickkopf-1 on bone turnover in young estrogen-sufficient women. © 2016, Springer Science+Business Media New York.

Summary: Thalassemia-associated osteoporosis constitutes a major complication in patients with thalassemia. This review presents the existing studies on the treatment of thalassemia-associated osteoporosis and discusses the management of this debilitating complication. A brief presentation of the disease characteristics and pathogenetic mechanisms is also provided. The life expectancy of patients with thalassemia has increased markedly in recent years resulting in the aging of the population and the emergence of new comorbidities. The majority of patients with thalassemia have low bone mineral density and experience lifelong fracture rates as high as 71 %. The pathogenesis of thalassemia-associated osteoporosis (TAO) is multifactorial with anemia and iron overload playing crucial role in its development. Data concerning the prevention and treatment of TAO are extremely limited. We performed a literature research in Pubmed and Scopus to identify interventional studies evaluating the effects of various agents on TAO. Seventeen studies were retrieved. We present the results of these studies as well as a brief overview of TAO including presentation, pathogenesis, and management. Most of the studies identified are of poor quality, are not randomized controlled, and include small number of participants. There are no data concerning effects on fracture rates. Bisphosphonates are the most widely studied agents and among them zoledronic acid is the most well studied. Hormone replacement treatment (HRT) shows beneficial but small effects. Denosumab and strontium ranelate have each been evaluated in only a single study, while there are no data about the effects of anabolic agents. Given the increased life expectancy and the increase in fracture rates with age, more data about the management of TAO are warranted. Moreover, due to the need for lifelong management starting at young age, careful treatment plans which may include sequential treatment may often be required. However, currently, there are no relevant data available. © 2016, International Osteoporosis Foundation and National Osteoporosis Foundation.

Background/Objective: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). Subjects/Methods: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). Results: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, PP=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, PPP=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders). Conclusions: Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could represent an additional biomarker, depicting the impact of altered hemodynamics on arterial wall.