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Osteocalcin is the most abundant noncollagenous protein of bone matrix. Once transcribed, this protein undergoes posttranslational modifications within osteoblastic cells before its secretion, including the carboxylation of three glutamic residues in glutamic acid, which is essential for hydroxyapatite binding and deposition in the extracellular matrix of bone. Recent provocative data from experimental observations in mice showed that the circulating undercarboxylated fraction of osteocalcin increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral fat in both genders, while it enhances testosterone production by the testes in males. Moreover, both total and undercarboxylated osteocalcins increase following physical activity with potential positive effects on glucose tolerance. Despite that these evidences have been only in part confirmed in humans, further prospective investigations are needed to definitively establish the endocrine role of osteocalcin both in the general population and cohorts of patients with diabetes or other metabolic disorders.

Natriuretic peptides (NPs) are entered in current guidelines for heart failure (HF) diagnosis and management because of their high specificity and sensibility in screening patients with acute dyspnea. Due to their availability and relatively low cost, they became the first step examinations in HF patients evaluation at hospital admission together with clinical and chest radiography examination. NPs are released following any cardiac haemodynamic stress due to volume or pressure overload and should be considered as a mirror of cardiac condition helping in recognizing patients with poor outcome. Moreover, the exact role of NPs in early HF stages, in isolated diastolic dysfunction, and in general population is questioned. Several promising reports described their potential role; however, the wide cut-off definition, inclusion criteria, and intrinsic measurement biases do not actually consent to their clinical application in these settings. A multimodality strategy including both NPs and imaging studies appears to be the best strategy to define the cardiac dysfunction etiology and its severity as well as to identify patients with higher risk. In this review, we describe the current and potential role of NPs in patients with asymptomatic cardiac insufficiency, evaluating the requirement to obtain a better standardization for imaging as for laboratory criteria.

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for 3 months, and had an areal bone mineral density (aBMD) T-score 1.5 standard deviations. Subjects received 20g/d teriparatide (n=45) or 35mg/week risedronate (n=47) for 18 months. Primary objective was to compare lumbar spine (L1L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p=0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005

Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. This enzyme is encoded by the CYP19A1 gene located at chromosome 15q21.2, that is, expressed in ovary and testis, but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone. Importantly, extraglandular aromatization of circulating androgen precursors is the major source of estrogen in men. Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, the attainment of peak bone mass, pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men.

Daniela Merlotti, Luigi Gennari, Giuseppe Martini, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, ItalyAbstract: Paget’s disease of bone (PDB) is a chronic bone remodeling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP) activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.Keywords: Paget’s disease of bone, bisphosphonates, aminobisphosphonates, bone remodeling

At present chronic diseases are of crucial importance for all health services in the Western World for both their epidemic prevalence and the fact that they absorb a growing proportion of health service financial resources. Osteoporosis has clinical and public health importance because osteoporotic fractures are one of the most common causes of disability and an important contributor to medical costs in many regions of the world Increased longevity has resulted in the emergence of age-related fragility fractures as a major public health problem. Today several classes of effective drugs are available for osteoporosis. However, these drugs to be effective, need to be taken long-term. In the case of BPs data have shown that nearly 70% of patients on a daily, and almost 60% on a weekly treatment, stop taking medication before the end of 1 year. A poor adherence is associated to an increased probability of fractures with consequent higher likelihood of hospitalisation and higher costs. Since reasons for nonadherence may depend on individual beliefs and circumstances the strategy to improve adherence should be tailored according to the individual patient. These findings underline the key role played by the physicians, above all GPs, in a strategy to improve adherence which now could be supported by the avaibility of new drugs and innovative administration routes.

The MURCS association [Müllerian Duct aplasia or hypoplasia (M), unilateral renal agenesis (UR) and cervicothoracic somite dysplasia (CS)] manifests itself as Müllerian Duct aplasia or hypoplasia, unilateral renal agenesis and cervicothoracic somite dysplasia. We report on a 22-year-old woman with bicornuate uterus, right renal agenesis, C2-C3 vertebral fusion (MURCS association) and 22q11.2 deletion. Angio-MRI revealed the aberrant origin of arch arteries. Hashimoto thyroiditis, micropolycystic ovaries with a dermoid cyst in the right ovary and mild osteoporosis were also diagnosed. Accurate revision of radiographs enabled us also to identify thoracolumbar and lumbosacral vertebral-differentiation defects. Audiometry and echocardiogram were normal. Bone densitometry showed osteoporosis. As per our evaluation, the patient had short stature, obesity (BMI 30.7) and facial features suggestive of the 22q11 deletion syndrome. Multiplex ligation-dependent probe amplification analysis showed a de-novo 22q11.2 deletion confirmed by array-comparative genomic hybridization analysis. We discuss whether this is a casual association or whether it is an additional syndrome owing to the well known phenotype extensive variability of the 22q11 deletion syndrome.

To evaluate serum levels of relaxin (RLX), a hormone with acknowledged antifibrotic activity, in patients with systemic sclerosis (SSc).We performed a pilot study of 50 outpatients with SSc and 50 healthy subjects. Serum RLX was measured using the relaxin ELISA. Statistical analysis was performed using Student's t test.Serum RLX appeared to be significantly higher (p0.001) in patients with SSc compared to controls. RLX appeared significantly increased (p0.001) in male patients compared to male controls, and in female patients compared to female controls. RLX was significantly higher (p0.001) in female patients and female controls compared to male patients and male controls.In patients with SSc, the increased level of RLX represents a defensive response against the fibrotic process.