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Purpose of Review: The purpose of this review is to summarize the recently published scientific evidence on the effects of diet on diabetes and skeletal health. Recent Findings: The impact of diet on overall health has been a growing topic of interest among researchers. An inappropriate eating habit is a relatively modified risk factor for diabetes in adults. Parallel with the significant increase in the incidence of diabetes mellitus worldwide, many studies have shown the benefits of lifestyle modifications, including diet and exercise for people with, or at risk of developing, diabetes. In the last years, accumulating evidence suggests that diabetes is a risk factor for bone fragility. As lifestyle intervention represents an effective option for diabetes management and treatment, there is potential for an effect on bone health. Summary: Healthy lifestyle is critical to prevent bone fragility. However, more studies are needed to fully understand the impact of diet and weight loss on fracture risk in diabetics. [ABSTRACT FROM AUTHOR]

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk. [ABSTRACT FROM AUTHOR]

Objective: The aim of our scoping review was to summarize the state of the art regarding micronutrients in order to identify which of them might effectively improve health status in the areas typically impaired in older people: bone, skeletal muscle, and cognitive function. Design: Scoping review. Methods: The Italian Study Group on Healthy Aging by Nutraceuticals and Dietary Supplements (HANDS) performed this scoping review, based on the following steps: doing a list of micronutrients related with musculoskeletal or cognitive functions, included in dietary supplements and nutraceuticals commercialized in Italy; planning a research on PubMed, according to an evidence-based approach, in order to the most relevant positive study for each micronutrient into each of the three areas involved (bone, skeletal muscle and cognitive function); identifying the micronutrients effective in maintaining or achieving an adequate health status in older people, specifying the effective and safe daily doses, according to the selected studies. Results: In literature we found 12 relevant positive studies (1 international society guidelines/recommendations, 1 systematic review, 7 randomized controlled trials, and 3 prospective cohort studies). We showed that only 16 micronutrients resulted to have appropriate scientific evidences in terms of improving musculoskeletal health and/or cognitive function in older people: beta-alanine, calcium, creatine, fluorides, leucine, magnesium, omega-3 fatty acids, potassium, vitamin B6, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K2, and zinc. Conclusion: This scoping review showed that selected micronutrients in adequate doses might have an ancillary role in musculoskeletal health and cognitive functions in older people. [ABSTRACT FROM AUTHOR]

Summary: Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014. [ABSTRACT FROM AUTHOR]

Summary: Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis. Introduction: Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis. Methods: In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum β-CrossLaps (CTX) were measured in the whole population. Results: Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26 ng/mL vs 0.29 ± 0.2 ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613 nmol/mL/h vs 472 ± 313 nmol/mL/h, p < 0.001, respectively) even after adjustment for age ( p < 0.001). Spearman correlation test revealed a negative correlation between Chit and BMD at each site (lumbar spine: r = −0.38, p = 0.001, femoral neck: r = −0.35, p = 0.001, total femur: r = −0.39, p < 0.001). Furthermore, a positive correlation between Chit and PTH was observed (r = 0.26, p = 0.013). No significant correlation was found between Chit and beta-CTX (r = 0.12, p = 0.229). After a multivariate analysis, a positive correlation between severe osteoporosis and Chit ( p < 0.001), beta-CTX ( p = 0.013), and age ( p < 0.001) was observed. Conclusion: This is the first clinical study showing a correlation between Chit and severe postmenopausal osteoporosis. Larger and prospective studies are needed to evaluate if Chit may be a promising clinical biomarker and/or therapeutic monitor in subjects with osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Introduction: Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. Methods: IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. Results: This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. Conclusions: This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs. [ABSTRACT FROM AUTHOR]

Fracture risk is higher in older adults with type 2 diabetes and may be influenced by treatments for diabetes. Oral anti-diabetic drugs have different effects on bone metabolism. The purpose of this review is to describe the effects of these drugs on bone metabolism and fracture risk. Osteoporosis is a progressive skeletal disorder that is characterized by compromised bone strength and increased risk of fracture. This condition has become an important global health problem, affecting approximately 200 million people worldwide. Another chronic and highly prevalent condition is diabetes mellitus, which affects more than 380 million people; both type 1 and type 2 diabetes are risk factors for fracture. Type 2 diabetes, in particular, is associated with impaired bone strength, although it is characterized by normal or elevated bone mineral density. Several therapeutic strategies are available to achieve the best outcomes in the management of diabetes mellitus but these have different effects on bone metabolism. The purpose of this narrative review is to describe the effects of oral hypoglycemic agents (metformin, sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-dependent glucose transporter 2 inhibitors) on bone metabolism and on the risk of developing fragility fractures in patients with type 2 diabetes. Both diabetes and osteoporosis represent a significant burden in terms of healthcare costs and quality of life. It is very important to choose therapies for diabetes that ensure good metabolic control whilst preserving skeletal health. [ABSTRACT FROM AUTHOR]

Background:Obesity exacerbates the age-related decline in insulin sensitivity and is associated with risk for cardiometabolic syndrome in older adults; however, the appropriate treatment for obese older adults is controversial.Objective:To determine the independent and combined effects of weight loss and exercise on cardiometabolic risk factors in obese older adults.Design:One-hundred and seven obese (body mass index (BMI)30 kg m−2) older (65 years) adults with physical frailty were randomized to control group, diet group, exercise group and diet-exercise group for 1 year. Outcomes for this study included changes in insulin sensitivity index (ISI), glucose tolerance, central obesity, adipocytokines and cardiometabolic syndrome.Results:Although similar increases in ISI occurred in the diet-exercise and diet groups at 6 months, the ISI improved more in the diet-exercise than in the diet group at 12 months (2.4 vs 1.2; between-group difference, 1.2; 95% confidence interval, 0.2-2.1); no changes in ISI occurred in both exercise and control groups. The diet-exercise and diet groups had similar improvements in insulin area under the curve (AUC) (−2.9 and −2.9 × 103 mg min dl−1), glucose AUC (−1.4 and −2.2 × 103mg min dl−1), visceral fat (−787 and −561 cm3), tumor necrosis factor (−17.0 and −12.8 pg ml−1), adiponectin (5.0 and 4.0 ng ml−1), waist circumference (−8.2 and −8.4 cm), triglyceride (−30.7 and −24.3 g dl−1) and systolic/diastolic blood pressure (−15.9 and −13.1/−4.9 and −6.7 mm Hg), while no changes in these parameters occurred in both exercise and control groups. The cardiometabolic syndrome prevalence decreased by 40% in the diet-exercise and by 15% in the diet group. Body weight decreased similarly in the diet-exercise and diet groups (−8.6 and −9.7 kg) but not in the exercise and control groups.Conclusions:In frail, obese older adults, lifestyle interventions associated with weight loss improve insulin sensitivity and other cardiometabolic risk factors, but continued improvement in insulin sensitivity is only achieved when exercise training is added to weight loss. [ABSTRACT FROM AUTHOR]

Summary: We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD. Introduction: Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise. Methods: One hundred seven obese older adults were randomized to control, diet, exercise, and diet-exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay. Results: Thigh muscle volume decreased in the diet group (−6.2 ± 4.8 %) and increased in the exercise group (2.7 ± 3.1 %), while it was not significantly different from the control in the diet-exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23 ± 20 %; 25 ± 19 %) and diet-exercise group (20 ± 19 %; 20.6 ± 27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD ( r = 0.55, P = <0.001) and were an independent predictor of changes in hip BMD ( β = 0.12, P = 0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no correlations between BMD changes and knee strength, 1-RM, and sclerostin changes. Conclusions: Changes in thigh muscle volume predict hip BMD changes in obese older patients undergoing lifestyle therapy. The effect of exercise in attenuating thigh muscle loss when added to diet may in part account for the reduction in weight loss-induced bone loss in the diet-exercise group. [ABSTRACT FROM AUTHOR]

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: In this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA. Methods: Collagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype. Results: Significantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients. Conclusion: Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA. [ABSTRACT FROM AUTHOR]

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. Introduction: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. Methods and results: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. Conclusions: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country. [ABSTRACT FROM AUTHOR]

The role of apoptosis in the persistence of hepatitis C virus (HCV) infection is controversial. Moreover, conflicting data on the modulation of this process by HCV proteins have been provided. We evaluated the susceptibility of peripheral lymphocytes from patients with chronic hepatitis C to apoptosis both spontaneous and after incubation with a chimeric Cucumber mosaic virus (CMV) carrying 180 copies of the synthetic R9 mimotope obtained from more than 200 hypervariable region-1 sequences of HCV. Resting T lymphocytes were found to be sensitized to apoptosis as a result of chronic HCV infection. The plant virus-derived vector R9-CMV displayed a strong pro-apoptotic effect associated with activation of both caspase-8 and −9, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. A parallel R9-CMV-mediated activation of endoplasmic reticulum-stress was suggested by the significant induction of BiP/GRP78, GADD153 and caspase-12. These data contribute to define the complex HCV/host interaction, and open new prospects for developing a plant-derived antigen-presenting system to strengthen host defences against persistent pathogens. [ABSTRACT FROM AUTHOR]

In the PREdiction of DIabetes from CApillary blood glucose (PREDICA) study, we propose a novel approach based on multiple capillary blood glucose (CBG) measurements, assuming that weekly measurements performed for 2 months may be an efficient strategy to screen for diabetes. We studied 538 Caucasian subjects (247 men and 291 women) without a history of diabetes, consecutively recruited by 50 GPs from the Italian provinces of Rome and Frosinone. Subjects were asked to perform 8 fasting glucose and 8 post-prandial glucose measurements during a frame time of 2 months (Glucometer Accu-chek AVIVA Roche Diagnostics). Study subjects were 55 ± 9 years old (range 22-77 years of age), 50% were overweight and 16% obese. Fifty-eight percent of subjects have performed 13 to 16 CBG measurements during the study, 68% of subjects have performed at least 5 out of 8, both fasting and post-prandial measurements. Among 492 subjects who had at least two fasting measurements, 63.6% had normal glucose levels, 25.4% showed IFG, and 11.0% were diabetic. Considering post-prandial measurements, 74.2% had normal glucose levels, 23.0% had IGT, and 2.8% were diabetic. Combined IFG + IGT was detected in 7% of study subjects, while in 0.8% diagnosis of diabetes was confirmed with both fasting and post-prandial measurements. In this study, we found a high adherence to a novel screening strategy based on self-glucose monitoring in the general population. Our results show that multiple CBG measurements may represent a simple and efficient method for diabetes screening. [ABSTRACT FROM AUTHOR]

Summary: This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. Clinical case reports/reviews and case-control studies report this association, but retrospective phase III trial analyses show no increased risk. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is yet unproven. Introduction: A Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation has reviewed the evidence for a causal association between subtrochanteric fractures and long-term treatment with bisphosphonates, with the aim of identifying areas for further research and providing recommendations for physicians. Methods: A PubMed search of literature from 1994 to May 2010 was performed using key search terms, and articles pertinent to subtrochanteric fractures following bisphosphonate use were analysed. Results: Several clinical case reports and case reviews report a possible association between atypical fractures at the subtrochanteric region of the femur in bisphosphonate-treated patients. Common features of these 'atypical' fractures include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal cortex and transverse fracture pattern. Some small case-control studies report the same association, but a large register-based study and retrospective analyses of phase III trials of bisphosphonates do not show an increased risk of subtrochanteric fractures with bisphosphonate use. The number of atypical subtrochanteric fractures in association with bisphosphonates is an estimated one per 1,000 per year. It is recommended that physicians remain vigilant in assessing their patients treated with bisphosphonates for the treatment or prevention of osteoporosis and advise patients of the potential risks. Conclusions: Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is unproven and requires further research. Were the case to be proven, the risk-benefit ratio still remains favourable for use of bisphosphonates to prevent fractures. [ABSTRACT FROM AUTHOR]

Copyright of La Radiologia Medica is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of La Radiologia Medica is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Reports of femoral shaft fractures in patients on long-term bisphosphonates (BPs) have raised important concerns on the safety for this class of drugs. Patients with malignancies are potentially at a higher risk for this complication considering the dose and the duration of treatment with BPs. In this report we describe the case of 56-year-old woman with multiple myeloma who developed a non-traumatic left femoral shaft fracture after treatment with high dose BPs for 6 years, following a bone marrow transplant. Intramedullary rod fixation of the fractured femur resulted in “splitting” of the fractured bone followed by poor healing and nonunion of the fractured bone. This case illustrates a potential problem in the management of patients with femoral shaft fractures from prolonged BPs, most especially those who are on high doses for malignant conditions. However, considering the number of patients who benefit from BPs, this complication should not discourage clinicians from using these agents in patients where treatment is indicated. [ABSTRACT FROM AUTHOR]

While bone mineral density (BMD) by dual-energy X-ray absorptiometry is the primary method of determining fracture risk, assessing bone turnover may add valuable information for the management of patients with low bone mass. Bone turnover markers (BTMs) are used in clinical trials where they can provide essential information on the biological efficacy of osteoporosis treatments. In such population-based studies, BTMs can predict fracture risk independent of BMD. When combined with BMD, they improve the fracture risk estimate above and beyond BMD alone in postmenopausal osteoporotic women. Since changes in bone turnover after the initiation of therapy with bone resorption inhibitors occur much more rapidly than changes in BMD, treatment efficacy could, in theory, be determined within weeks of using BTMs. However, such predictive value is limited by the large biological variability of these biochemical markers, even though newer automated methods have reduced their analytical variability. Consequently, widespread adoption as a means of predicting treatment efficacy in fracture prevention for individual patients cannot yet be recommended. BTMs may be useful for monitoring adherence to antiresorptive therapy and may aid in identifying patients for whom antiresorptive therapy is most appropriate. Thus, although BTMs are currently confined to clinical research applications, further improvement in assay precision may extend their diagnostic value in clinical settings. [ABSTRACT FROM AUTHOR]

Estrogen is a critical hormone for bone homeostasis in men, but no information is available on the role of estrogen metabolism among men. The aim of this study was to evaluate the effect of estrogen hydroxylation on male bone mineral density (BMD). Participants consisted of 61 healthy Caucasian males (mean age 66.6 +/- 1.0 years). Urinary estrogen metabolites were measured by enzyme-linked immunosorbent assay, serum estradiol by ultrasensitive radioimmunoassay, sex hormone binding globulin by radioimmunoassay, and BMD of the lumbar spine and the proximal femur by dual-energy X-ray absorptiometry. Active estrogen metabolites, 16alpha-hydroxyestrone (16alphaOHE(1)) and estriol (E(3)), positively correlated with adjusted BMD in all regions of the proximal femur (all P < 0.05) but not at the lumbar spine, and those in the highest tertile of urinary 16alphaOHE(1 )had the highest BMD. Free estradiol index (FEI) also positively correlated with BMD of the total hip, femoral neck, and intertrochanter (all P < 0.05), while there was no correlation between BMD with inactive metabolites (2-hydroxyestrone and 2-methoxyestrone) and serum testosterone. Multiple regression analysis showed 16alphaOHE(1), FEI, and body mass index are important independent predictors of BMD in all regions of the proximal femur. Estrogen metabolism may modulate BMD in men. Increased urinary 16alphaOHE(1) and E(3) levels are associated with high BMD at the proximal femur, and 16alphaOHE(1) appears to be a major determinant of BMD among the metabolites evaluated. [ABSTRACT FROM AUTHOR]

One of the most promising genetic approaches to dissecting a multifactorial disease is represented by genetically isolated population studies. We studied a genetic marker in a cohort of women living on the Mediterranean island of Lampedusa, a geographically isolated population. Lampedusa, located between the African coast and Sicily, consists of a young genetic isolate (<20 generations) with an exponential growth in the last generations. We analyzed the association between the FokI vitamin D receptor (VDR) gene polymorphism, previously proposed as a predictor of bone mass, with parameters of bone mass and turnover in a cohort of pre- and postmenopausal women living on Lampedusa. In 424 women (277 postmenopausal and 147 premenopausal), allelic frequencies were 49% for the F allele and 51% for the f allele. Using analysis of covariance, we found that subjects with ff genotype exhibited a significantly (P < 0.001) lower lumbar spine bone mass, by dual-energy X-ray absorptiometry, and lower values of bone ultrasonographic parameters (speed of sound and broadband ultrasound attenuation) relative to those with Ff and FF genotypes. Conversely, osteocalcin and serum cross-laps were significantly higher in ff and Ff compared to FF genotype. Our data suggest that FokI VDR polymorphism may contribute to the determination of bone mass and turnover in both pre- and postmenopausal women in this geographically isolated population. [ABSTRACT FROM AUTHOR]

We studied bone mass and metabolism in 30 adult women (age 28.5 ± 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 ± 0.31; femoral neck -0.60±0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 ± 0.2, femoral neck -1.83 ± 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 ± 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual. [ABSTRACT FROM AUTHOR]

A correction to the article "Taxonomy of Rare Genetic Metabolic Bone Disorders" that was published in the 2015 issue is presented.

An correction to the article "Serum chitotriosidase in postmenopausal women with severe osteoporosis" that was published online in the January 19, 2016 issue is presented.