Impact of nutrition on muscle mass, strength, and performance in older adults.

Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate [corrected] relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B12 and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging.

An appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

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.

A global representation of vitamin D status in healthy populations.

PURPOSE: This paper visualizes the available data on vitamin D status on a global map, examines the existing heterogeneities in vitamin D status and identifies research gaps. METHODS: A graphical illustration of global vitamin D status was developed based on a systematic review of the worldwide literature published between 1990 and 2011. Studies were eligible if they included samples of randomly selected males and females from the general population and assessed circulating 25-hydroxyvitamin D [25(OH)D] levels. Two different age categories were selected: children and adolescents (1-18 years) and adults (>18 years). Studies were chosen to represent a country based on a hierarchical set of criteria. RESULTS: In total, 200 studies from 46 countries met the inclusion criteria, most coming from Europe. Forty-two of these studies (21 %) were classified as representative. In children, gaps in data were identified in large parts of Africa, Central and South America, Europe, and most of the Asia/Pacific region. In adults, there was lack of information in Central America, much of South America and Africa. Large regions were identified for which the mean 25(OH)D levels were below 50 nmol/L. CONCLUSIONS: This study provides an overview of 25(OH)D levels around the globe. It reveals large gaps in information in children and adolescents and smaller but important gaps in adults. In view of the importance of vitamin D to musculoskeletal growth, development, and preservation, and of its potential importance in other tissues, we strongly encourage new research to clearly define 25(OH)D status around the world.

Treatment failure in osteoporosis.

UNLABELLED: Guidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided. INTRODUCTION: This study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture. METHODS: A working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making. RESULTS: In the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease. CONCLUSION: The provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.

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.

A systematic review of hip fracture incidence and probability of fracture worldwide.

UNLABELLED: The country-specific risk of hip fracture and the 10-year probability of a major osteoporotic fracture were determined on a worldwide basis from a systematic review of literature. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries. INTRODUCTION: The present study aimed to update the available information base available on the heterogeneity in the risk of hip fracture on a worldwide basis. An additional aim was to document variations in major fracture probability as determined from the available FRAX models. METHODS: Studies on hip fracture risk were identified from 1950 to November 2011 by a Medline OVID search. Evaluable studies in each country were reviewed for quality and representativeness and a study (studies) chosen to represent that country. Age-specific incidence rates were age-standardised to the world population in 2010 in men, women and both sexes combined. The 10-year probability of a major osteoporotic fracture for a specific clinical scenario was computed in those countries for which a FRAX model was available. RESULTS: Following quality evaluation, age-standardised rates of hip fracture were available for 63 countries and 45 FRAX models available in 40 countries to determine fracture probability. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries. CONCLUSIONS: Worldwide, there are marked variations in hip fracture rates and in the 10-year probability of major osteoporotic fractures. The variation is sufficiently large that these cannot be explained by the often multiple sources of error in the ascertainment of cases or the catchment population. Understanding the reasons for this heterogeneity may lead to global strategies for the prevention of fractures.

A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis.

UNLABELLED: 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.

Interpretation and use of FRAX in clinical practice.

UNLABELLED: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review INTRODUCTION: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. METHODS: This study reviews the resource documents and joint position statements of ISCD and IOF. RESULTS: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. CONCLUSIONS: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures.

Vertebral compression fractures (VCFs) are the most prevalent fractures in osteoporotic patients. The classical conservative management of these fractures is through rest, pain medication, bracing and muscle relaxants. The aim of this paper is to review prospective controlled studies comparing the efficacy and safety of minimally invasive techniques for vertebral augmentation, vertebroplasty (VP) and balloon kyphoplasty (BKP), versus non-surgical management (NSM). The Fracture Working Group of the International Osteoporosis Foundation conducted a literature search and developed a review paper on VP and BKP. The results presented for the direct management of osteoporotic VCFs focused on clinical outcomes of these three different procedures, including reduction in pain, improvement of function and mobility, vertebral height restoration and decrease in spinal curvature (kyphosis). Overall, VP and BKP are generally safe procedures that provide quicker pain relief, mobility recovery and in some cases vertebral height restoration than conventional conservative medical treatment, at least in the short term. However, the long-term benefits and safety in terms of risk of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting. Referral physicians should be aware of VP/BKP and their potential to reduce the health impairment of patients with VCFs. However, VP and BKP are not substitutes for appropriate evaluation and treatment of osteoporosis to reduce the risk of future fractures.

Coordinator-based systems for secondary prevention in fragility fracture patients.

The underlying causes of incident fractures--bone fragility and the tendency to fall--remain under-diagnosed and under-treated. This care gap in secondary prevention must be addressed to minimise both the debilitating consequences of subsequent fractures for patients and the associated economic burden to healthcare systems. Clinical systems aimed at ensuring appropriate management of patients following fracture have been developed around the world. A systematic review of the literature showed that 65% of systems reported include a dedicated coordinator who acts as the link between the orthopaedic team, the osteoporosis and falls services, the patient and the primary care physician. Coordinator-based systems facilitate bone mineral density testing, osteoporosis education and care in patients following a fragility fracture and have been shown to be cost-saving. Other success factors included a fracture registry and a database to monitor the care provided to the fracture patient. Implementation of such a system requires an audit of existing arrangements, creation of a network of healthcare professionals with clearly defined roles and the identification of a 'medical champion' to lead the project. A business case is needed to acquire the necessary funding. Incremental, achievable targets should be identified. Clinical pathways should be supported by evidence-based recommendations from national or regional guidelines. Endorsement of the proposed model within national healthcare policies and advocacy programmes can achieve alignment of the objectives of policy makers, professionals and patients. Successful transformation of care relies upon consensus amongst all participants in the multi-disciplinary team that cares for fragility fracture patients.

Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards.

UNLABELLED: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies. INTRODUCTION: Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda. METHODS: Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001. RESULTS: High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine. CONCLUSION: BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.

Global vitamin D status and determinants of hypovitaminosis D.

UNLABELLED: This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. INTRODUCTION: Vitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. METHODS: Six regions of the world were reviewed-Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania-through a survey of published literature. RESULTS: The definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75 nmol/L are prevalent in every region studied whilst levels below 25 nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. CONCLUSION: Reports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.

Collagen-hydroxyapatite composites for hard tissue repair.

Bone is the most implanted tissue after blood. The major solid components of human bone are collagen (a natural polymer, also found in skin and tendons) and a substituted hydroxyapatite (a natural ceramic, also found in teeth). Although these two components when used separately provide a relatively successful mean of augmenting bone growth, the composite of the two natural materials exceeds this success. This paper provides a review of the most common routes to the fabrication of collagen (Col) and hydroxyapatite (HA) composites for bone analogues. The regeneration of diseased or fractured bones is the challenge faced by current technologies in tissue engineering. Hydroxyapatite and collagen composites (Col-HA) have the potential in mimicking and replacing skeletal bones. Both in vivo and in vitro studies show the importance of collagen type, mineralisation conditions, porosity, manufacturing conditions and crosslinking. The results outlined on mechanical properties, cell culturing and de-novo bone growth of these devices relate to the efficiency of these to be used as future bone implants. Solid free form fabrication where a mould can be built up layer by layer, providing shape and internal vascularisation may provide an improved method of creating composite structures.

The use of immunocytochemical techniques for the detection of steroid hormones in breast cancer cells.

Indirect immunofluorescence and immunoperoxidase assays were developed to detect estradiol and progesterone in breast cancer cells. Appropriate controls were used to confirm immunologic specificity. Studies of estradiol binding by human breast cancer cells identified three groups: no detectable binding (25%); all tumor cells exhibiting binding although to different degrees (4%); and tumors with varying numbers of positive and negative cells (71%). Similar observations were made with respect to progesterone binding. The percentage of cells with estradiol binding was correlated with the amount of estrogen receptors (ER) present in the tumor specimens. Post-hormone binding events e.g., nuclear binding of estradiol, were also evaluated. Some tumor cells showing cytoplasmic binding of estradiol did not show nuclear binding of estradiol; such tumors lacked detectable diethylstilbestrol under routine assay conditions, and relatively high concentrations of estradiol were needed to observe estradiol-specific staining. The results suggest that the immunocytochemical assays detect hormone-specific binding, but that the binding is probably due to multiple classes of steroid-binding sites.