Dietary Vitamin D Intake in Italian Subjects: Validation of a Frequency Food Questionnaire (FFQ).

Vitamin D plays a crucial role in calcium and phosphate metabolism, relating to bone health and preventing metabolic bone disorders such as rickets and osteomalacia. Vitamin D deficiency (serum 25-OH-D values <20 ng/mL or 50 nmol/L) is common also in Italian people; it is recommended to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. Supplementation and/or fortification with either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) aimed to modify this condition have commonly been proposed. Studies about vitamin D intake are numerous in the literature but not adequately designed and are very often incomplete in Mediterranean Countries such as in the Italian population. On these bases, we performed a survey to validate a frequency food questionnaire (FFQ) specifically created to rapidly assess dietary vitamin D intake in Italian people. For this aim, the data of questionnaires were compared with results derived in the same population from a designed 14-day frequency food diary (FFD). Overall, a good correlation between FFQ and FFD was observed (r = 0.89, p < 0.001), both demonstrating a remarkably low vitamin D intake, irrespective of age and gender. Our data confirm that the vitamin D intake is very low in Italy, which likely contributes to hypovitaminosis D.

Vitamin D and adrenal gland: Myth or reality? A systematic review.

In recent years, vitamin D has become the protagonist in many studies. From cardiology to oncology the spotlight was on this vitamin. While in the past it was considered for its important role in phospho-calcium metabolism and skeletal disorders; today by studying it better, thousands of scenarios and facets have opened up on this vitamin which is actually a hormone in all respects. There are authoritative studies that demonstrate its activity in vitro and in vivo on: carcinogenesis, inflammation, autoimmunity and endocrinopathies. Its role has been studied in type 1 and type 2 diabetes mellitus, in Hashimoto or Graves' thyroiditis and even in adrenal gland diseases. In fact, there are several studies that demonstrate the possible correlations between vitamin D and: Addison's disease, Cushing disease, hyperaldosteronism or adrenocortical tumors. Moreover, this fascinating hormone and adrenal gland even seem to be deeply connected by common genetic pathways. This review aimed to analyze the works that have tried to study the possible influence of vitamin D on adrenal diseases. In this review we analyze the works that have tried to study the possible influence of vita-min D on adrenal disease.

A subgroup analysis of the ODYSSEY APPRISE study: Safety and efficacy of alirocumab in the Italian cohort.

BACKGROUND AND AIMS: ODYSSEY APPRISE trial evaluated efficacy and safety of alirocumab in 994 patients with hypercholesterolemia and high CV risk in a real-life setting. The aim of the present report is to detail on the Italian cohort enrolled and treated in the trial. METHODS AND RESULTS: The methodology of the of the multinational, single-arm, Phase 3b open-label ODYSSEY APPRISE (Clinicaltrials.gov: NCT02476006) has been previously reported. 255 Italian patients were enrolled and treated according to the trial protocol. Overall mean exposure to alirocumab was 83.3 ± 27.7 weeks. At week 12, LDL-C decreased by 51.3 ± 23.1% and this reduction was overall maintained for the duration of the study. A similar reduction was observed in patients with and without heterozygous familial hypercholesterolemia (HeFH 50.7% ± 23.9 vs. non-FH, 53.6% ± 19.6). LDL-C was reduced below 1.8 mmol/L and/or by ≥ 50% reduction from baseline in 62% of patients overall (61% in HeFH and 67% in non-FH). Alirocumab was similarly well tolerated in the Italian cohort as in the entire study population and the more common treatment emergent adverse events (TEAEs) were influenza, myalgia and nasopharyngitis. The incidence LDL-C levels <25 mg/dl and <15 mg/dl, was 8.2% and 2.9% respectively. CONCLUSION: The efficacy and safety of alirocumab in a real-life setting, in the Italian subgroup of patients are consistent with findings in the entire study population and confirm that alirocumab is a beneficial approach to further reduce LDL-C levels in patients at high CV risk on maximally tolerated conventional lipid lowering treatment. GOV IDENTIFIER: NCT02476006.

Persistence and recurrence in tumor-induced osteomalacia: A systematic review of the literature and results from a national survey/case series.

PURPOSE: Tumor induced osteomalacia (TIO) is a rare disease of mineral metabolism, whose clinical picture is dominated by hypophosphatemia usually due to an excess of circulating FGF23 produced by small mesenchymal tumors. Data on the real prevalence of the disease are lacking, with the knowledge of the disease mainly relying on case reports and small case series. No estimate is available on the prevalence of uncured TIO. METHODS: National multi-center, cross-sectional and retrospective study on persistent or recurrent cases of TIO followed in referral centers for bone diseases; systematic review of the published persistent and recurrent cases of TIO. Data from patients consecutively evaluated in referral Italian centers for bone diseases were collected; a PubMed search on persistent, recurrent and unoperable cases of TIO was carried out. RESULTS: Sixteen patients (mean age at diagnosis 52.5 ± 10.6 years) with persistent (n = 6, 37,5%), recurrent (n = 7, 43.7%) or not operable (n = 3, 18.8%) TIO were described. Delay in diagnosis (2.5 ± 1.3 years) was demonstrated. All patients experienced fragility fractures or pseudofractures and disabling bone and muscle pain. BMD was significantly reduced (mean T-score -2.7 ± 1.7 and -2.7 ± 0.9 at lumbar spine and femoral neck, respectively). Fourteen patients were maintained under therapy with phosphate salts and calcitriol, while in 2 patients therapy with burosumab, an anti-FGF23 antibody, was commenced. CONCLUSION: A significant number of patients with TIO remain either undiagnosed for tumor localization or tumor recur or persist after surgery. These patients with active disease represent possible candidates for burosumab treatment.

Combined Surgical and Medical Treatment for Vancouver B1 and C Periprosthetic Femoral Fractures: A Proposal of a Therapeutic Algorithm While Retaining the Original Stable Stem.

INTRODUCTION: There is lack of consensus regarding best operative fixation strategy for periprosthetic femoral fractures (PFFs) around a stable stem. Evidence exists that some patterns of fracture around a stable stem are better treated with revision surgery than with standard fixation. Anyway, a more aggressive surgical procedure together with medical treatment could allow for stem retention, and reduced risk of nonunion/hardware failure, even in these cases. SIGNIFICANCE: This paper is placed in a broader context of lack of studies on the matter, and its aim is to shed some light on the management of PFFs around a stable stem, when peculiar mechanical and biological aspects are present. RESULTS: Based on our casuistry in the treatment of nonunions after PFF successfully treated with original stem retention, and on review of Literature about risk factors for fixation failure, an algorithm is proposed that can guide in choosing the ideal surgical technique even for first-time PFFs with a stable stem, without resorting to revision. Mechanical (major and minor) and biological (local and systemic) factors that may influence fracture healing, leading to nonunion and hardware failure, and subsequent need for re-operation, are considered. The proposed surgical technique consists of rigid fixation with absolute stability (using a plate and structural allograft) plus local biological support (structural allograft and autologous bone marrow concentrate over a platelet-rich plasma-based scaffold) at fracture site. Systemic anabolic treatment (Teriparatide) is also administered in the post-operative period. CONCLUSION: Mechanical factors are not the only issues to be considered when choosing the surgical approach to PFFs over a stable stem. Systemic and local biological conditions should be taken into account, as well. A therapeutic algorithm is proposed, given the prosthetic stem to be stable, considering mechanical and biological criteria.

Hypercalciuria in Sarcoidosis: A Specific Biomarker With Clinical Utility.

Background: Changes in calcium metabolism are quite common in sarcoidosis: hypercalciuria is linked to a persistent clinical phenotype and more active disease. No data is yet available on the specificity of parameters of calcium metabolism as biomarkers for distinguishing different chronic interstitial lung diseases (ILD). Here we assessed calcium metabolism in an Italian population of sarcoidosis patients, which included a group with stage IV fibrotic disease, and compared the results with those of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (cHP) patients. Population and Methods: We recruited sarcoidosis, IPF and cHP patients retrospectively. All patients were diagnosed through multidisciplinary discussion and were monitored at the Regional ILD Referral Centre in Siena. Clinical, radiological, functional, immunological and laboratory parameters were collected and entered in an electronic database for data analysis. Results: A total of 305 patients (237 sarcoidosis, 40 IPF and 28 cHP) were enrolled. Sarcoidosis patients included a predominance of females and were significantly younger than IPF and cHP patients (p < 0.0001 for both). In the sarcoidosis population, 17 patients (7.2%) showed radiological evidence of lung fibrosis, according the Scadding classification; fibrotic disease was also confirmed by CT scan. Concerning calcium metabolism, sarcoidosis patients showed significantly higher serum and urinary concentrations of calcium than IPF and cHP patients (p = 0.0004 and p < 0.0001, respectively). These findings were also confirmed when comparing groups with fibrotic sarcoidosis, IPF and cHP (p = 0.0237 and p = 0.0138). According to receiver operating characteristics (ROC) curve analysis, urinary calcium showed better diagnostic accuracy than serum calcium in discriminating sarcoid and non-sarcoid lung fibrosis (AUC 0.7658 vs. 0.6205; p = 0.0026 vs. p = 0.1820). Discussion: Our results confirmed that changes in calcium metabolism, particularly hypercalciuria, occur in a substantial percentage of patients with sarcoidosis. Higher serum and urinary concentrations of calcium were found than in IPF and cHP; the same results were observed when the comparison was limited to patients with fibrotic sarcoidosis, supporting the hypothesis that dysregulation of calcium metabolism may be a special feature of sarcoid granulomas. Hypercalciuria distinguished fibrotic sarcoidosis from IPF and cHP, suggesting that assessment of calcium metabolism may be useful in the diagnostic pathway of ILDs.

Calcification of Cardiac Valves in Metabolic Bone Disease: An Updated Review of Clinical Studies.

Epidemiological and clinical data have suggested the existence of a relationship between cardiovascular diseases and metabolic bone disease. Several studies have demonstrated that heart valve calcification presents substantial similarities with that of bone. Literature data indicate that there are many active processes which promote osteogenesis and loss of mineralization inhibitors that lead to the deposition of extracellular matrix and proteins of bone tissue in cardiac valves. This review aimed to synthesize the available data in order to allow a better understanding of the relationship between osteoporosis or other metabolic bone diseases, such as primary hyperparathyroidism, and valvular calcification in humans. Electronic databases of Pubmed-Medline, Cochrane Library, and SCOPUS from inception to March 31, 2019 were searched. The full set of the articles potentially eligible were carefully assessed and reviewed. Finally, 23 studies were eligible and included in the systematic review. The majority of studies reported that osteoporosis and/or osteopenia were independent risk factors for valvular calcifications, even after adjusting for common cardiovascular risk factors. This suggests that this relationship is not only due to the presence of common cardiovascular risk factors but rather to underlying biological factors that connect them. Instead, regarding the association between primary hyperparathyroidism and valve calcification, conflicting data were found in the literature. To sum up, most of the literature data confirm that cardiac valve calcification processes are strongly influenced by alterations in bone metabolism. In particular, the patients with osteoporosis or primary hyperparathyroidism have an acceleration in the process of valvular calcification. Additional studies are needed to specifically address the mechanisms by which metabolic bone diseases could influence cardiac valve calcification.

Cow's Milk Consumption and Health: A Health Professional's Guide.

The most recent scientific evidence supports the consumption of cow's milk and dairy products as part of a balanced diet. However, these days, the public and practicing physicans are exposed to a stream of inconsistent (and often misleading) information regarding the relationship between cow's milk intake and health in the lay press and in the media. The purpose of this article, in this context, is to facilitate doctor-patient communication on this topic, providing physicians with a series of structured answers to frequently asked patient questions. The answers range from milk and milk-derived products' nutritional function across the life span, to their relationship with diseases such as osteoporosis and cancer, to lactose intolerance and milk allergy, and have been prepared by a panel of experts from the Italian medical and nutritional scientific community. When consumed according to appropriate national guidelines, milk and its derivatives contribute essential micro- and macronutrients to the diet, especially in infancy and childhood where bone mass growth is in a critical phase. Furthermore, preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes, and cardiovascular disease, while no clear data suggest a significant association between milk intake and cancer. Overall, current scientific literature suggests that an appropriate consumption of milk and its derivatives, according to available nutritional guidelines, may be beneficial across all age groups, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy. Key teaching points: Milk and its derivatives contribute essential micro and macronutrients to the diet, when consumed according to appropriate national guidelines, especially in infancy and childhood where bone mass growth is in a critical phase. Preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes and cardiovascular disease No clear data are available about the association between milk intake and cancer. Current scientific literature suggests that an appropriate consumption of milk and its derivatives may be beneficial at all ages, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy.

Histopathological findings in systemic sclerosis-related myopathy: fibrosis and microangiopathy with lack of cellular inflammation.

OBJECTIVES: The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients. METHODS: A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor ß (TGF-ß)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of (n = 35) idiopathic inflammatory myopathies (IIMs) and to (n = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM). RESULTS: Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, p < 0.05) and with NIM (18%, p < 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, p < 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM (p < 0.05) and with NIM (p < 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM (p < 0.05) and NIM (p < 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM (p < 0.05), characterized by CD4+/CD8+/B-cell infiltrate, and NIM (p < 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell 'swelling' coupled to endomysial/perimysial fibrosis. CONCLUSIONS: Fibrosis, microangiopathy and humoral immunity are predominant in SSc myopathy, even if it is difficult to identify specific histopathological hallmarks of muscle involvement in SSc, since they could be present also in other (IIM/NIM) myopathies.

Idiopathic pulmonary fibrosis a rare disease with severe bone fragility.

Idiopathic pulmonary fibrosis (IPF) is a rare form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The aim of this cross-sectional study was to assess the prevalence of osteoporosis and fragility fracture in a population of adults with IPF and to identify whether any possible clinical and pulmonary function parameters may be associated with increased bone fragility. In 58 IPF patients (mean age 65.1 ± 9.1 years), we measured bone mineral density (BMD) of the lumbar spine, the femoral neck, and the entire hip. Moreover, the presence of vertebral fractures on a lateral chest X-ray study was evaluated, and a vertebral fracture burden was quantified using the spinal deformity index (SDI). As expected, osteoporosis was significantly more frequent in females with respect to males (57.9 vs 20.5 %, respectively), whereas the fractures prevailed in males with respect to females (38.5 vs 26.3 %, respectively). There were positive correlations between BMD at all skeletal sites and respiratory parameters; in particular for FVC % and DLCO % with BMD at femoral sub-regions. Moreover, we compared the average of DLCO (%) measure by values of SDI score that was higher in those patients with lower values of DLCO (%). The study shows a high prevalence of fragility with vertebral fractures in IPF patients, especially in males. Moreover, the vertebral fracture burden is associated with a worsening of FVC (%) and DLCO (%). Therefore, an evaluation of bone status is recommended, especially in those patients who are candidates for lung transplantation.

The Trochanteric Localization is a Mediator of Slower Short-Term Functional Recovery in Overweight and Obese Elderly Women with Recent Hip Fracture: The BREAK Study.

The hypothesis tested in this study, carried out on elderly Italian women with recent hip fracture, was to assess the extent to which the effect of a condition of being overweight/obese on short-term functional recovery as evaluated by the "time to permitted load" could be explained by a mediator variable (type of hip fracture). We studied 727 women aged 60 years or over with a recent low trauma surgically treated hip fracture and for whom an information on post-surgery complications and on the time to permitted load was available. To assess for mediation, the statistical analyses were carried out following the procedure described by Baron and Kenny. In this study, 46 % of women with hip fracture presented a time to permitted load of ≥ 10 days. The women with a post-surgery time to permitted load of ≥ 10 days showed a significantly higher proportion of trochanteric fracture localization (72.1 vs 42 %), of total overweight/obesity (46.5 vs 36.8 %) and of post-surgery complications (38.8 vs 18.8 %). The mediating effect of hip fracture localization on the association between overweight/obesity and the time of permitted load was demonstrated and confirmed in a multivariate logistic regression model. This study, carried out using a "mediator" statistical analysis, suggests that in elderly women with hip fracture being overweight/obese is associated with a slower short-term functional recovery as evaluated by the time to permitted load and that this association is mediated by the trochanteric localization of hip fracture.

Sperm Parameters and Semen Levels of Inflammatory Cytokines in Helicobacter pylori-infected Men.

OBJECTIVE: To explore the relationships between seminal interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) with semen parameters, sperm apoptosis, and necrosis in subjects infected by Helicobacter pylori (HP) expressing and not expressing CagA. METHODS: In 109 selected patients, HP infection and seminal levels of IL-6 and TNF-α were determined using enzyme-linked immunosorbent assays. Western blotting was used to detect antibodies to CagA. Semen parameters were determined following World Health Organization guidelines and sperm apoptosis and necrosis by annexin V and propidium iodide assay. RESULTS: Twenty-eight subjects were infected by HP (HP+); among them, 12 were CagA seropositive (CagA+) and 16 were negative (CagA-). Eighty-one men were HP seronegative (HP-). Semen TNF-α and IL-6 concentrations were increased in HP+ vs HP- groups (TNF-α: 41 pg/mL vs 27 pg/mL; IL-6: 11 pg/mL vs 5 pg/mL; P <.01). In comparison to the HP- group, CagA+ group showed reduced sperm motility (24% vs 32% motile sperm; P <.05), enhanced necrosis (33.5% vs 21% necrotic sperm; P <.05), and increased cytokines levels (TNF-α: 46 pg/mL vs 27 pg/mL; P <.01; IL-6: 17.5 pg/mL vs 5 pg/mL; P <.01). Sperm motility of CagA+ group was lower vs CagA- group (24% vs 36.5% motile sperm; P <.05). Both IL-6 and TNF-α levels positively correlated with the percentage of necrotic sperm (P <.001). CONCLUSION: CagA+ HP infection increases semen levels of inflammatory cytokines, which may reduce sperm motility and determine sperm damage and contribute to reduce the reproductive potential in men.

Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction.

Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p < 0.04) and a more significant decrease of BNP levels in respect to the iIV group (679.6 ± 397 vs 949 ± 548 pg/ml, p < 0.04). We observed a significant increase in creatinine levels (1.78 ± 0.5 vs 1.41 ± 0.3 mg/dl, p < 0.01), and a reduction of the estimated glomerular filtration rate in cIV (44.8 ± 6.1 vs 46.7 ± 6.1 ml/min, p < 0.05). We observed a significant difference in eGFR (p = 0.01), creatinine (p = 0.02) and BNP levels (p = 0.03) from baseline to the end of treatment in both groups. A significant increase of in-hospital additional treatment as well as length of hospitalization was observed in cIV. Finally, cIV revealed a higher rate of adverse events during the follow-up period (p < 0.03). cIV appears to provide a more efficient diuresis and BNP level reduction during hospitalization, however, it was associated with increased rate of worsening renal function during hospitalization. cIV also appears related to a longer hospitalization and an increased number of adverse events during follow-up. For all of these reasons, a larger multi-center study is required to determine whether high-dose diuretics are responsible for worsening renal function and to define the best modality of administration.

The burden of previous fractures in hip fracture patients. The Break Study.

A positive history of fractures in older patients with hip fracture is common. We determined the risk factors associated with a positive history of fractures and the profile of care in hip fracture patients. In the Break Study, we enrolled 1249 women aged ≥60 years, seeking care for a hip fracture. Baseline information included age, body mass index, lifestyle (smoking habit, alcohol consumption), patient's history of fracture after the age of 50 years, family history of fragility fracture and health status (presence of comorbidity, use of specific drugs, pre-fracture walking ability, type of fracture, time to surgery, type of surgery, osteoporosis treatment). In the multivariable model age, smoking, family history, treatment with antiplatelet, anticoagulants and anticonvulsants, were significant predictors of a positive history of fracture. More than 70% of patients underwent surgery more than 48 hours after admission. About 50% were discharged with a treatment for osteoporosis, but more than 30% only with calcium and vitamin D. In conclusion, factors associated with a positive history of fracture are the traditional risk factors, suggesting that they continue to have a negative impact on health even at older ages. Selected drugs, such as antiplatelet and anticoagulants, deserve further consideration as significant factors associated with fractures. Given that delay in surgery is a major cause of mortality and disability, while treatment for osteoporosis decreases significantly the risk of recurrent fractures and disability, interventions to modify these patterns of care are urgently needed.

Quantitative ultrasound and dual-energy x-ray absorptiometry in children and adolescents with neurofibromatosis of type 1.

Reduced areal bone mineral density (aBMD) is a common feature of neurofibromatosis type 1 (NF1). Moreover, in recent years there has been a growing interest in using quantitative ultrasound (QUS) for the evaluation of bone status. In 55 NF1 subjects (mean age: 9.3+/-5.4yr) and in 51 age- and sex-matched controls we measured aBMD at lumbar spine, at femoral neck (aBMD-FN), and at total femur (aBMD-T). Apparent volumetric bone mineral density (BMAD) was also calculated. In all subjects, QUS parameters at phalanges were evaluated. In NF1 subjects, the values of aBMD and BMAD were lower than in controls at all skeletal sites, but the difference reached statistical significance only at femoral sites (p<0.05). Both aBMD and QUS parameters were lower in those NF1 subjects with skeletal abnormalities than in those without abnormalities, but the difference was statistically significant (p<0.05) only for aBMD-FN and aBMD-T. Multiple regression analysis showed that the subjects with skeletal abnormalities had a higher risk of having bone transmission time (BTT) Z-score and aBMD Z-score at femoral sites less than -1. In conclusion, our results suggest that aBMD and QUS represent useful tools in evaluating the impairment of bone status in NF1 subjects.

Osteoprotegerin and B-type natriuretic peptide in acute coronary syndromes with preserved systolic function: relation to coronary artery disease extension.

OBJECTIVES: To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. METHODS: 155 CAD patients were classified in four groups: stable angina (SA n=42), unstable angina (UA n=35) non-ST elevation myocardial infarction (NSTEMI n=45) and control group (n=33), measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels were higher in patients with CAD respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with UA and NSTEMI had higher OPG level with respect to SA patients (12.2+/-7.8 and 11.6+/-6.1 respectively pmol/l p<0.001). A positive relation was found between OPG levels and coronary plaques extension by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with UA/NSTEMI respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in patients with multi-vessels vs 1-vessel disease (p<0.001). CONCLUSIONS: Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the CAD progression.

Aromatase inhibitors, efficacy and metabolic risk in the treatment of postmenopausal women with early breast cancer.

The third-generation aromatase inhibitors (AIs), letrozole, anastrozole and exemestane, are becoming the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen in both adjuvant and metastatic setting. In particular, several large and well designed trials have suggested an important role for AIs in the adjuvant treatment of postmenopausal women with estrogen-receptor positive breast cancer either in the upfront, sequential or extended adjuvant mode. Overall, AIs are associated with a small but significant improvement in disease free survival. The expanding use of AIs in the treatment of early breast cancer means that individual patients will be exposed to the agents for longer durations, making it increasingly important to establish their long-term safety. This review focused on the effects of AIs on bone metabolism, serum lipids and cardiovascular risk. AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures. With respect to tamoxifen AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified. An adequate monitoring of bone mineral density (BMD) and lipid profile could be recommended for post-menopausal women candidate to AIs.

A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: effects on bone metabolism.

Current evidence suggests that estrogen plays a dominant role in determining bone mineral density (BMD) in men, and inactivating mutations in the aromatase CYP19 gene have been associated with low bone mass in young males. We previously reported an association between a TTTA repeat polymorphism in intron 4 of the CYP19 gene and osteoporotic risk in postmenopausal females. Here we explore the role of this polymorphism as a genetic determinant of BMD in a sample of elderly males who were recruited by direct mailing and followed longitudinally for 2 (n = 300) and 4 (n = 200) yr. Six different allelic variants, containing seven, eight, nine, 10, 11, and 12 TTTA repeats, were detected. There was a bimodal distribution of alleles, with two major peaks at seven and 11 repeats and a very low distribution of the nine-repeat allele. Men with a high-repeat genotype (>nine repeats) showed higher lumbar BMD values, lower bone turnover markers, higher estradiol levels, and a lower rate of BMD change than men with a low-repeat genotype (25), suggesting that the effect of CYP19 genotypes on bone may be masked by the increase in fat mass. Moreover, the high-repeat genotype was less represented, although not significantly, in the vertebral fracture group with respect to the nonvertebral fracture group. Functional in vitro analysis after incubation with [3H]-androstenedione showed a higher aromatase activity in fibroblasts from subjects with a high-repeat genotype than in fibroblasts from subjects with a low-repeat genotype. In conclusion, differences in estrogen levels due to polymorphism at the aromatase CYP19 gene may predispose men to increased age-related bone loss and fracture risk.

Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men.

Male osteoporosis is an increasingly important health problem. It is known that sex steroid hormones play an important role in regulating bone turnover and bone mass in males as well as in females. However, the exact mechanism of bone loss in men remains unknown. In the present study, 200 elderly men (age range, 55-85 yr) were followed for 4 yr to evaluate the relationships between hormone levels, bone turnover markers, bone mineral density, and rates of bone loss. Femoral and lumbar bone mineral density, bone ultrasound parameters at the os calcis, serum testosterone (T), serum estradiol (E(2)), SHBG levels, and bone turnover markers (urinary crosslaps and bone alkaline phosphatase) were evaluated for each man at enrollment and 4 yr afterward. The free androgen index (FAI) and free estrogen index (FEI) as well as measures of the bioavailable sex hormones [calculated bioavailable E(2) (c-bioE(2)) and T (c-bioT)] were calculated from total hormone levels and SHBG. In the total population, T, c-bioT, c-bioE(2), FAI, and FEI, but not E(2), decreased significantly with age, whereas SHBG increased significantly. Subjects with FEI, c-bioE(2), and E(2) levels below the median showed higher rates of bone loss at the lumbar spine and the femoral neck as well as higher speed-of-sounds decrease at the calcaneus with respect to men with FEI, c-bioE(2), and E(2) levels above the median. Serum bone alkaline phosphatase and urinary crosslaps were significantly higher in men with FEI, c-bioE(2), and E(2) in the lower quartile than in men with FEI, c-bioE(2), and E(2) levels in the higher quartile. No statistically significant differences were observed in relation to T, c-bioT, or FAI levels. Finally, the ratio between E(2) and T, an indirect measure for aromatase activity, increased significantly with age and was higher in normal than in osteoporotic subjects. In conclusion, results from the present study indicate an important role of estrogens, and particularly of the ability to aromatize T to E(2), in the regulation of bone loss and bone metabolism in elderly men.