Influence of state-of-the-art laboratory techniques on the phenotyping of women with polycystic ovary syndrome in the clinical setting.

PURPOSE: Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice. METHODS: In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH. RESULTS: The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)]. CONCLUSIONS: Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.

Prevalence of Vertebral Fractures and Non-fracture Deformities in Healthy Adult Men: The Importance of Morphologic Criteria.

Vertebral fractures (VF) are common in older men but data on VF prevalence in young men is limited. The aim of this study was to describe the prevalence of VF and non-fracture vertebral deformities (VD) in healthy young to middle-aged men, and compare the characteristics of men with normal vertebrae, VF and VD. In this cross-sectional study, vertebral fracture assessment by dual-energy X-ray absorptiometry was performed in 650 men, aged 32 to 60 years (mean 46.2), from the population-based SIBLOS-SIBEX cohort. For VF and VD assessment, both the modified algorithm-based qualitative approach (morphologic criteria) to discriminate VF from VD and the semi-quantitative (morphometric) grading system of Genant (GSQ) were used. We found 48 (0.6%) fractured vertebrae, of which 15 were classified grade 1, 29 grade 2 and 4 grade 3 VF. There were 378 (4.7%) VD, of which 296 were scored grade 1, 82 grade 2 and none grade 3 VD. Twenty-six participants (4%) had VF, 15 had one and 11 had 2 or more VF. Two hundred and twenty-eight (35.1%) men had VD. Femoral neck, total hip and lumbar spine areal bone mineral density (aBMD) were lower in men with VF than in those with normal vertebrae or VD. Men with VD, in turn, had aBMD values similar to men with normal vertebrae. Our results suggest that -even in young healthy men-using the GSQ without taking qualitative aspects into account overestimates VF prevalence, confirming the importance of morphologic criteria to correctly diagnose and distinguish VF from VD.

Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis?

We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.

Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF).

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. INTRODUCTION: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. METHODS: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. RESULTS: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. CONCLUSION: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.

The role of calcium supplementation in healthy musculoskeletal ageing : An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF).

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

Osteoporosis in Frail Patients: A Consensus Paper of the Belgian Bone Club.

In this consensus paper, the Belgian Bone Club aims to provide a state of the art on the epidemiology, diagnosis, and management of osteoporosis in frail individuals, including patients with anorexia nervosa, patients on dialysis, cancer patients, persons with sarcopenia, and the oldest old. All these conditions may indeed induce bone loss that is superimposed on physiological bone loss and often remains under-recognized and under-treated. This is of particular concern because of the major burden of osteoporotic fractures in terms of morbidity, mortality, and economic cost. Therefore, there is an urgent need to appreciate bone loss associated with these conditions, as this may improve diagnosis and management of bone loss and fracture risk in clinical practice.

The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

Lower insulin sensitivity is related to lower relative muscle cross-sectional area, lower muscle density and lower handgrip force in young and middle aged non-diabetic men.

OBJECTIVES: This study investigated whether an association between insulin resistance (IR) and muscle parameters is appreciable in young healthy men, independent of obesity. Furthermore, markers of muscle metabolism and hormones/possible determinants, were explored. METHODS: 358 healthy young men were divided into a less and more insulin sensitive (LIS [age=33.2±5.4, BMI=23.4±2.3] and MIS [age=35.5±5.3, BMI=28.1±3.7]) group based on upper and lower quartile of HOMA-IR. Muscle cross-sectional area (CSA), -density, handgrip force, serum testosterone, estradiol, SHBG, Vitamin 25(OH)D, creatinine, IGF-1, IGFBP-3 and leptin levels were compared between these groups, correcting for differences in age, physical activity and fat mass. Correlations between HOMA-IR and these parameters, and between muscle measures and biochemical parameters, were calculated. RESULTS: LIS is related to lower relative muscle CSA, muscle density, muscle/fat CSA ratio, relative handgrip force and level of physical activity. Furthermore, lower levels in SHBG, testosterone, Vitamin 25(OH)D and higher leptin, IGF-1 and IGFBP-3 levels were observed in LIS. Bio available T, FT, TE2, FE2, bioavailable E2, serum and urinary creatinine levels did not differ between groups. CONCLUSION: Differences in muscle performance are already present in healthy men with lower insulin sensitivity and could be possibly modifiable risk factors for the development of type 2 diabetes.

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

UNLABELLED: Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. PURPOSE: The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. METHODS: In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-ß estradiol 100 µg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. RESULTS: Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). CONCLUSIONS: Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Taxonomy of rare genetic metabolic bone disorders.

UNLABELLED: 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.

Goal-directed treatment of osteoporosis in Europe.

UNLABELLED: Despite the proven predictive ability of bone mineral density, Fracture Risk Assessment Tool (FRAX®), bone turnover markers, and fracture for osteoporotic fracture, their use as targets for treatment of osteoporosis is limited. INTRODUCTION: Treat-to-target is a strategy applied in several fields of medicine and has recently become an area of interest in the management of osteoporosis. Its role in this setting remains controversial. This article was prepared following a European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group meeting convened under the auspices of the International Osteoporosis Foundation (IOF) to discuss the feasibility of applying such a strategy in osteoporosis in Europe. METHODS: Potential targets range from the absence of an incident fracture to fixed levels of bone mineral density (BMD), a desired FRAX® score, a specified level of bone turnover markers or indeed changes in any one or a combination of these parameters. RESULTS: Despite the proven predictive ability of all of these variables for fracture (particularly BMD and FRAX), their use as targets remains limited due to low sensitivity, the influence of confounders and current lack of evidence that targets can be consistently reached. CONCLUSION: ESCEO considers that it is not currently feasible to apply a treat-to-target strategy in osteoporosis, though it did identify a need to continue to improve the targeting of treatment to those at higher risk (target-to-treat strategy) and a number of issues for the research agenda. These include international consensus on intervention thresholds and definition of treatment failure, further exploration of the relationship between fracture and BMD, and FRAX and treatment efficacy and investigation of the potential of short-term targets to improve adherence.

Association between insulin resistance, lean mass and muscle torque/force in proximal versus distal body parts in healthy young men.

OBJECTIVES: The purpose of this study was to investigate whether there is already an association of insulin resistance (IR) with muscle mass and -force/torque in an adult population and whether this relationship is the same in distal and proximal body parts. METHODS: 358 Healthy young men were divided into a more insulin sensitive (MIS) (n=89) and a less insulin sensitive (LIS) group (n=89), respectively using lower and upper quartiles of HOMA-IR index (Homeostasis Model Assessment of IR). Muscle force/torque and lean mass, were compared between the two groups. RESULTS: LIS subjects had higher absolute thigh lean mass, but not higher thigh muscle torque, resulting in a lower torque per kg muscle. In upper arm, lean mass was higher in LIS subjects, but also absolute muscle torque resulted higher. For handgrip force, the LIS and MIS group had similar results, despite a trend towards higher forearm lean mass in LIS subjects. Lean mass % of total lean mass is lower in LIS subjects in more distal body parts. CONCLUSIONS: Already in a young healthy population, IR seems to be associated with lower force/torque per muscle mass and lower lean mass % of total lean mass predominantly in more distal body parts.

An evaluation of the Fracture Risk Assessment Tool (FRAX®) as an indicator of treatment efficacy: the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX®.

SUMMARY: The relationship between baseline Fracture Risk Assessment Tool (FRAX®) and treatment efficacy was evaluated using data from a pivotal phase 3 study. Relative risk of vertebral, nonvertebral, and all clinical fractures decreased with increasing probability of fracture for bazedoxifene (BZA) versus placebo but remained generally constant for raloxifene (RLX). INTRODUCTION: To determine whether the FRAX® predicts osteoporosis treatment efficacy, we evaluated reductions in fracture incidence associated with BZA and RLX according to baseline fracture risk determined by FRAX® using data from a phase 3 osteoporosis treatment study. METHODS: Hazard ratios (HRs) for effects of BZA and RLX versus placebo on incidence of vertebral, nonvertebral, and all clinical fractures were calculated using a Cox regression model. Cox regression analyses were performed in subgroups at or above 10-year fracture probability thresholds determined by FRAX®. RESULTS: HRs for the risk of vertebral, nonvertebral, and all clinical fractures versus placebo decreased with increasing 10-year fracture probability for BZA, while those for RLX remained stable. In all 10-year fracture probability subgroups, all BZA doses significantly reduced vertebral fracture risk versus placebo (HR = 0.22-0.66). BZA at 20, 40, and 20/40 mg significantly reduced risk of nonvertebral fractures (HR = 0.45, 0.44, and 0.45, respectively) and all clinical fractures (HR = 0.38, 0.41, and 0.40, respectively) for ≥20.0 % fracture probability. Vertebral fracture risk reductions for RLX 60 mg versus placebo were significant in subgroups at lower fracture probabilities (≥2.5- ≥ 10.0 %), but not higher (≥12.5 %), and in no subgroups for nonvertebral or all clinical fractures. CONCLUSION: The antifracture efficacy of BZA increased with increasing baseline FRAX® score, but there was no clear relationship between RLX and baseline FRAX®. These findings provide independent confirmation of current literature, suggesting that the relationship between FRAX® and treatment efficacy varies for different agents.

Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications.

UNLABELLED: Drugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection. INTRODUCTION: The therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound. METHODS: The present document is the result of a national consensus, based on a systematic and critical review of the literature. RESULTS: Observational research has suggested an inverse relationship between calcium intake and cardiovascular diseases, notably through an effect on blood pressure, but recent data suggest a possible deleterious effect of calcium supplements on cardiovascular risk. Many diverse studies have implicated vitamin D in the pathogenesis of clinically important non-skeletal functions or diseases, especially muscle function, cardiovascular disease, autoimmune diseases and common cancers. The possible effects of oral or intravenous bisphosphonates are well-known. They have been associated with an increased risk of oesophageal cancer or atrial fibrillation, but large-scale studies have not found any association with bisphosphonate use. Selective oestrogen receptor modulators have demonstrated favourable or unfavourable extra-skeletal effects that vary between compounds. Strontium ranelate has a limited number of non-skeletal effects. A reported increase in the risk of venous thromboembolism is not found in observational studies, and very rare cases of cutaneous hypersensitivity reactions have been reported. Denosumab has been introduced recently, and its extra-skeletal effects still have to be assessed. CONCLUSION: Several non-skeletal effects of bone drugs are well demonstrated and influence treatment choices.

A reappraisal of generic bisphosphonates in osteoporosis.

UNLABELLED: The competitive price of generic bisphosphonates has had a marked effect on practice guidelines, but an increasing body of evidence suggests that they have more limited effectiveness than generally assumed. INTRODUCTION: The purpose of this study is to review the impact of generic bisphosphonates on effectiveness in the treatment of osteoporosis. METHODS: This study is a literature review. RESULTS: A substantial body of evidence indicates that many generic formulations of alendronate are more poorly tolerated than the proprietary preparations which results in significantly poorer adherence and thus effectiveness. Poorer effectiveness may result from faster disintegration times of many generics that increase the likelihood of adherence of particulate matter to the oesophageal mucosa. Unfortunately, market authorisation, based on the bioequivalence of generics with a proprietary formulation, does not take into account the potential concerns about safety. The poor adherence of many generic products has implications for guideline development, cost-effectiveness and impact of treatment on the burden of disease. CONCLUSIONS: The impact of generic bisphosphonates requires formal testing to re-evaluate their role in the management of osteoporosis.

Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis.

UNLABELLED: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.

Osteoporosis in young adults: pathophysiology, diagnosis, and management.

Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score ≤ -2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below -2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this condition.

Assessment of health claims in the field of bone: a view of the Group for the Respect of Ethics and Excellence in Science (GREES).

UNLABELLED: Health claims for food products in Europe are permitted if the nutrient has been shown to have a beneficial nutritional or physiological effect. This paper defines health claims related to bone health and provides guidelines for the design and the methodology of clinical studies to support claims. INTRODUCTION: Regulation (EC) no. 1924/2006 on nutrition and health claims targeting food products was introduced in Europe stating that health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. The objective of this paper is to define health claims related to bone health and to provide guidelines for the design and the methodology of clinical studies which need to be adopted to assert such health claims. METHODS: Literature review followed by a consensus discussion during two 1-day meetings organized by the Group for the Respect of Ethics and Excellence in Science (GREES). RESULTS: The GREES identified six acceptable health claims related to bone health based on the potential of food products to show an effect on either the bioavailability of calcium or osteoclast regulatory proteins or bone turnover markers or bone mineral density or bone structure or fracture incidence. The GREES considers that well-designed human randomized controlled trial on a relevant outcome is the best design to assess health claims. The substantiation of health claim could also be supported by animal studies showing either an improvement in bone strength with the food product or showing the relationship between changes induced by the food product on a surrogate marker and changes in bone strength. CONCLUSION: The consensus reached is that the level of health claim may differ according to the surrogate endpoint used and on additional animal studies provided to support the claim.

Frailty and sarcopenia: definitions and outcome parameters.

An operational definition of musculoskeletal decline in older people is needed to allow development of interventions for prevention or treatment, as was developed for the treatment of osteoporosis. Frailty and sarcopenia are linked, but distinct, correlates of musculoskeletal aging that have many causes, including age-related changes in body composition, inflammation, and hormonal imbalance. With the emergence of a number of exciting candidate therapies to retard the loss of muscle mass with aging, the derivation of a consensual definition of sarcopenia and physical frailty becomes an urgent priority. Although several consensual definitions have been proposed, these require clinical validation. An operational definition, which might provide a threshold for treatment/trial inclusion, should incorporate a loss of muscle mass as well as evidence of a decrease in muscle strength and/or physical activity. Evidence is required for a link between improvements in the measures of muscle strength and/or physical activity and clinical outcomes to allow development of interventions to improve clinical outcomes in frail older patients.

The relationship between paediatric calcaneal quantitative ultrasound measurements and dual energy X-ray absorptiometry (DXA) and DXA with laser (DXL) as well as body composition.

BACKGROUND: Quantitative ultrasound (QUS) is a quick, non-invasive and inexpensive method to measure bone strength. Moreover, the device is portable, which makes it easy to be used in the field. In contrast to other bone measuring techniques, QUS does not use any ionised radiation. However, the validity of QUS in the measurement of bone health and the relationship between QUS output and body composition have not been assessed in very young children. OBJECTIVE: To investigate the relationship between paediatric calcaneal QUS and both dual-energy X-ray absorptiometry (DXA) and calcaneal DXA with laser (DXL) and body composition parameters. SUBJECTS: A total of 37 Belgian children (10 boys and 27 girls; 4 to 8 years old) underwent a calcaneal QUS as well as a DXA scan. A total of 24 Swedish children (15 boys and 9 girls; 3 to 5 years old) underwent a calcaneal QUS as well as a heel DXL scan. The height and weight of all children were measured. RESULTS: The QUS stiffness index (SI) was significantly negatively correlated with bone mineral density (BMD) of the total body (r=-0.370, P=0.02). No significant correlations were found between the SI and DXL results. In the total sample, the SI showed a significant positive correlation with body mass index (BMI) (r=0.298, P=0.02), even after correction for age, gender and centre. In the Belgian sample, the SI was also significantly positively correlated with total body fat mass content (r=0.416, P=0.01) and body fat percentage (r=0.566, P<0.01) obtained by whole-body DXA. CONCLUSION: The SI measured by QUS does not correlate significantly with BMD values measured by DXA or DXL in 3- to 8-year-old children. However, there is a significant positive correlation between SI and BMI and body fat %.