Dietary supplementation with glycosaminoglycans reduces locomotor problems in broiler chickens.

This study aimed to assess the influence of glycosaminoglycan (chondroitin and glucosamine sulfates) supplementation in the diet on the performance and incidence of locomotor problems in broiler chickens. A completely randomized design was carried out in a 3 × 3 factorial scheme (3 levels of chondroitin sulfate -0, 0.05, and 0.10%; and 3 levels of glucosamine sulfate -0, 0.15, and 0.30%). Each treatment was composed of 6 replications of 30 broilers each. The performance of broilers (average weight, weight gain, feed intake, feed conversion, and productive viability) was assessed at 7, 21, 35, and 42 d of age, whereas the gait score, valgus and varus deviations, femoral degeneration, and tibial dyschondroplasia were assessed at 21 and 42 d of age. Increasing levels of glucosamine sulfate inclusion linearly increased the weight gain from 1 to 35 and from 1 to 42 d of age of broilers (P = 0.047 and P = 0.039, respectively), frequency of broilers with no femoral degeneration in the right and left femurs, and the proliferating cartilage area of proximal epiphysis at 42 d of age (P = 0.014, P < 0.0001, and P = 0.028, respectively). The increasing inclusion of chondroitin and glucosamine sulfates led to an increase in the frequency of broilers on the gait score scale 0 (P = 0.007 and P = 0.0001, respectively) and frequency of broilers with no valgus and varus deviations (P = 0.014 and P = 0.0002, respectively) also at 42 d of age. Thus, chondroitin and glucosamine sulfates can be used in the diet of broiler chickens to reduce their locomotor problems.

Use of cement combined grafting in upper and lower extremity benign bone tumors.

OBJECTIVES: This study aims to investigate the effectivity of cement combined demineralized bone matrix (DBM) treatment on new bone formation in the cortical window as well as to evaluate the effect of new bone formation on functional outcomes. PATIENTS AND METHODS: Thirty-two benign bone tumor patients (15 males, 17 females; median age 38 years; range, 12 to 68 years), who were treated with cement combined DBM between February 2010 and December 2014, were evaluated retrospectively. Patient characteristics were recorded as age, gender, tumor localization, histological diagnosis, Enneking stage, tumor size, size of the cortical window, usage of prophylactic fixation, time to return to work, Musculoskeletal Tumor Society (MSTS) functional score, tumor relapse, and new bone formation on the cortical window in the computed tomography scans after one year of surgery. RESULTS: Median tumor volume was 17.2 cm3 (range, 2.8 to 139.6 cm3), median area of the cortical window was 8.3 cm2 (range, 1.6 to 28.4 cm2), and median postoperative one-year MSTS score was 84.5 (range, 66 to 97). MSTS scores were significantly worse with the usage of prophylactic fixation (p<0.001). There was a statistically significant difference between the usage of prophylactic fixation and cortical window size (p=0.013). There was a low-level negative correlation in terms of age and bone formation on the cortical window (p=0.046, r= -0.356) and mid-level negative correlation between cortical window size and functional scores (p=0.001, r= -0.577). CONCLUSION: Application of cement combined with DBM procedure is an effective, alternative, and biological treatment in bone tumors that provides immediate stability and stimulates new bone formation on the cortical window.

Antiresorptive and anabolic agents in the prevention and reversal of bone fragility.

Bone volume, microstructure and its material composition are maintained by bone remodelling, a cellular activity carried out by bone multicellular units (BMUs). BMUs are focally transient teams of osteoclasts and osteoblasts that respectively resorb a volume of old bone and then deposit an equal volume of new bone at the same location. Around the time of menopause, bone remodelling becomes unbalanced and rapid, and an increased number of BMUs deposit less bone than they resorb, resulting in bone loss, a reduction in bone volume and microstructural deterioration. Cortices become porous and thin, and trabeculae become thin, perforated and disconnected, causing bone fragility. Antiresorptive agents reduce fracture risk by reducing the rate of bone remodelling so that fewer BMUs are available to remodel bone. Bone fragility is not abolished by these drugs because existing microstructural deterioration is not reversed, unsuppressed remodelling continues producing microstructural deterioration and unremodelled bone that becomes more mineralized can become brittle. Anabolic agents reduce fracture risk by stimulating new bone formation, which partly restores bone volume and microstructure. To guide fracture prevention, this Review provides an overview of the structural basis of bone fragility, the mechanisms of remodelling and how anabolic and antiresorptive agents target remodelling defects.

[Update 2017 of the KDIGO guidelines on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). What are the real changes?]

Guidelines for the assessment, diagnosis and therapy of the alterations that characterize the CKD-MBD are an important support in the clinical practice of the nephrologist. Compared to the KDIGO guidelines published in 2009, the 2017 update made changes on some topics on which there was previously no strong evidence both in terms of diagnosis and therapy. The recommendations include the diagnosis of bone anomalies in CKD-MBD and the treatment of mineral metabolism abnormalities with particular regard to hyperphosphataemia, calcium levels, secondary hyperparathyroidism and anti-resorptive therapies. The Italian Study Group on Mineral Metabolism, in reviewing the 2017 recommendations, aimed to assess the weight of the evidence that led to this update. In fact, on some topics there has not been a substantial difference on the degree of evidence compared to the previous guidelines. The Italian Study Group emphasizes the points that may still reserve critical issues, including interpretation, and invites an evaluation that is articulated and personalized for each patient.

Bone demineralization is improved by ivacaftor in patients with cystic fibrosis carrying the p.Gly551Asp mutation.

Low bone mineral density (BMD) is a common problem in adults with cystic fibrosis (CF), the etiology of which is multifactorial. In this study, we provide the first evidence that ivacaftor improves BMD in CF patients carrying the p.Gly551Asp mutation. Consistently, in vitro experiments with TNF-α-stimulated primary F508del-CFTR osteoblasts demonstrated that correction of p.Phe508del-CFTR markedly decreased RANKL protein production, a major factor of bone resorption. These clinical and fundamental observations suggest that rescue of mutated CFTR protein improves bone remodeling and support the link between CFTR and bone cell physiology. These findings represent a step forward in the development of potential new therapies for CF-related bone disease.

AAV8-mediated expression of N-acetylglucosamine-1-phosphate transferase attenuates bone loss in a mouse model of mucolipidosis II.

Mucolipidoses II and III (ML II and ML III) are lysosomal disorders in which the mannose 6-phosphate recognition marker is absent from lysosomal hydrolases and other glycoproteins due to mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Both disorders are caused by the same gene, but ML II represents the more severe phenotype. Bone manifestations of ML II include hip dysplasia, scoliosis, rickets and osteogenesis imperfecta. In this study, we sought to determine whether a recombinant adeno-associated viral vector (AAV2/8-GNPTAB) could confer high and prolonged gene expression of GNPTAB and thereby influence the pathology in the cartilage and bone tissue of a GNPTAB knock out (KO) mouse model. The results demonstrated significant increases in bone mineral density and content in AAV2/8-GNPTAB-treated as compared to non-treated KO mice. We also showed that IL-6 (interleukin-6) expression in articular cartilage was reduced in AAV2/8-GNPTAB treated ML II mice. Together, these data suggest that AAV-mediated expression of GNPTAB in ML II mice can attenuate bone loss via inhibition of IL-6 production. This study emphasizes the value of the MLII KO mouse to recapitulate the clinical manifestations of the disease and highlights its amenability to therapy.

Incremento de la densidad mineral ósea en pacientes con hiperparatiroidismo terciario tras paratiroidectomía total y autotrasplante de glándula paratiroides / Increased bone mineral density in patients with tertiary hyperparathyroidism after total parathyroidectomy and autotransplantation of the parathyroid gland

Introducción En los pacientes trasplantados renales con hiperparatiroidismo terciario se observan alteraciones del metabolismo óseo así como un descenso de la densidad mineral ósea. El objetivo de este trabajo fue analizar el incremento de la densidad mineral ósea, así como los resultados analíticos tras la paratiroidectomía total y autotrasplante en pacientes trasplantados renales con hiperparatiroidismo terciario. Material y métodos Estudio retrospectivo en el que se analizaron los valores de la densidad mineral ósea a nivel femoral y lumbar, así como los niveles séricos de calcio, fósforo, hormona paratiroidea (PTH) y fosfatasa alcalina en 13 pacientes trasplantados renales con hiperparatiroidismo terciario antes y después de la realización de paratiroidectomía total y autotrasplante de glándula paratiroides. Resultados La paratiroidectomía se asoció a un incremento de la densidad mineral ósea a nivel femoral y a nivel lumbar. El incremento de la densidad mineral ósea a nivel lumbar fue de 8,6±6,7% y de 4±16,1% a nivel femoral. El descenso de calcio tras la paratiroidectomía fue de 2,8mg/dl (IC 95%:1,9-4). El descenso de PTH fue de 172pg/mL (IC 95%:98-354) y el descenso de fosfatasa alcalina fue de 229 U/l (IC 95%:70-371).Conclusiones La paratiroidectomía total y el autotrasplante de glándula paratiroides en pacientes trasplantados renales con hiperparatiroidismo terciario incrementa la densidad mineral ósea. Asimismo, se observa una normalización de las cifras de calcio, PTH y fosfatasa alcalina a largo plazo (AU)

Introduction Changes in bone metabolism and bone mineral density are observed in renal transplant patients with tertiary hyperparathyroidism. The objective of this work was to analyse the increase in bone mineral density, as well the laboratory results, after total parathyroidectomy and autotransplantation in renal transplant patients with tertiary hyperparathyroidism. Material and methods A retrospective study was conducted in which the bone mineral density values at femoral and lumbar level were analysed, together with the serum levels of calcium, phosphorous, parathyroid hormone (PTH), and alkaline phosphatase in 13 renal transplant patients with tertiary hyperparathyroidism before and after total parathyroidectomy and autotransplantation of the parathyroid glands. Results Parathyroidectomy is associated with an increase in bone mineral density at femoral and lumbar level, with an increase of 8.6±6.7% at lumbar level, and 4±16.1% at femoral level. The decrease in calcium after the parathyroidectomy was 2.8mg/dL (95% CI; 1.9-4). The decrease in PTH was 172pg/mL (95% CI; 98-354) and the decrease in alkaline phosphatase was 229 U/L (95% CI; 70-371).Conclusions Total parathyroidectomy and autotransplantation of the parathyroid glands in renal transplant patients with tertiary hyperparathyroidism increases the bone mineral density. Furthermore, the calcium, PTH and alkaline phosphatase returned to normal in the long-term (AU)

Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.

More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500 million years ago with the boney fish (i.e., teleosts) that do not contain SIBLING proteins. In terrestrial vertebrates, FGF23, like SIBLING proteins, is expressed in the osteocyte. The boney fish, however, are an-osteocytic, so a physiological bone-renal link with FGF23 and the SIBLINGs was cemented when life ventured from the oceans to the land during the Triassic period, approximately 300 million years ago. This link has been revealed by recent research that indicates a competitive displacement of a PHEX-DMP1 interaction by an ASARM peptide that leads to increased FGF23 expression. This review discusses the new discoveries that reveal a novel PHEX, DMP1, MEPE, ASARM peptide, and FGF23 bone-renal pathway. This pathway impacts not only bone formation, bone-renal mineralization, and renal phosphate homeostasis but also energy metabolism. The study of this new pathway is relevant for developing therapies for several diseases: bone-teeth mineral loss disorders, renal osteodystrophy, chronic kidney disease and bone mineralization disorders (CKD-MBD), end-stage renal diseases, ectopic arterial-calcification, cardiovascular disease renal calcification, diabetes, and obesity.

Metabolic osteopathy in celiac disease: importance of a gluten-free diet.

Reduced bone mineral density (BMD) is frequently found in individuals with untreated celiac disease (CD), possibly due to calcium and vitamin D malabsorption, release of pro-inflammatory cytokines, and misbalanced bone remodeling. A gluten-free diet (GFD) promotes a rapid increase in BMD that leads to complete recovery of bone mineralization in children. Children may attain normal peak bone mass if the diagnosis is made and treatment is given before puberty, thereby preventing osteoporosis in later life. A GFD improves, but rarely normalizes, BMD in patients diagnosed with CD in adulthood. In some cases, nutritional supplementation may be necessary. More information on therapeutic alternatives is needed.

Diabetes mellitus and bone disease in cystic fibrosis.

Patients with cystic fibrosis are frequently affected with pancreatic insufficiency and are predisposed to the development of diabetes mellitus (DM) and bone demineralization. Cystic fibrosis-related diabetes mellitus is a clinical entity distinct from type 1 and type 2 diabetes, with important implications for the nutritional and pulmonary health of cystic fibrosis patients. This form of diabetes owes largely to insulin deficiency, but alterations in insulin sensitivity and hepatic glucose production have also been described. Therapy for cystic fibrosis-related diabetes differs substantially from type 2 DM, with careful attention to prandial glycemic excursions crucial to controlling its metabolic effects. Bone disease, including osteopenia and osteoporosis, also occurs with increased frequency in cystic fibrosis, owing to defects in intestinal absorption, chronic inflammation, lung disease, low body weight, and gonadal dysfunction. The pathogenesis, implications, diagnosis, and therapy of cystic fibrosis-related bone demineralization are discussed, with attention to recommended approaches to prevention of and treatment of established bone disease.

[Recommendations for the management of bone demineralization in cystic fibrosis]. / Recommandations pour la prise en charge de la déminéralisation osseuse dans la mucoviscidose.

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

Growth factors--BMPs, DBMs, and buffy coat products: are there any proven differences amongst them?

Advances in the understanding of bone repair and improved biotechnology have led to the introduction of new strategies for orthopedic surgeons to control and modulate bone healing using growth factors. However, many orthopedic surgeons are uncertain about the current levels of evidence supporting the use of materials that possess these properties and their therapeutic role in the management of skeletal problems such as fracture, long-bone nonunion, and spine fusion. In particular, the differences amongst osteoinductive factors synthesized by recombinant gene technology, or derived from demineralized bone matrix or platelet rich plasma requires clarification.

Indicaciones y tratamiento de la osteoporosis: el futuro que nos espera / Indications and treatment of osteoporosis: the future that awaits us

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The importance of exercising in space.

As a direct consequence of exposure to microgravity, astronauts experience a set of physiological changes which can have serious medical implications when they return to earth. Most immediate and significant are the headward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) following flight, decreased cardiac output, and reduced capacity for exercise. Changes in the musculoskeletal system contribute significantly to impaired function experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity, and countermeasures are therefore designed primarily to simulate earthlike movements, stresses, and system interactions. Exercise is one approach that has had wide operational use and acceptance in both the US and Russian space programmes, and it has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will be necessary for missions of longer duration, for example for human exploration of Mars.

Ejercicio y hueso: revisión bibliográfica / Exercise and bone. Bibliographic rewiew

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[Bone demineralization in Crohn's disease, its diagnosis, therapy and prevention]. / Demineralizace kostí u m. Crohn, její diagnostika, lécba a prevence.

In 20-60% of patients with Crohn's disease bone demineralization is found, usually osteoporosis, but also osteoporosis with malatic features. The cause is the reduced calcium intake (loss of appetite, lactose intolerance and malabsorption), reduced vitamin D intake and corticoid therapy. Nowadays the diagnosis is facilitated by the use of densitometers (ultrasonic and DEXA) and markers of osteoresorption and new bone formation. In treatment in addition to calcium and vitamin D used for a long time, fluorides are administered (only as monofluorophosphate), nasal thyrocalcitonin and bisphosphonates of the third series (alendronate). In postmenopausal women also hormonal treatment can be used unless contraindicated. However, burdening of the bones with regular exercise is a necessity. For prevention adequate calcium and vitamin D intake is important, non-smoking, and exercise.

Bone mineralization, hypothalamic amenorrhea, and sex steroid therapy in female adolescents and young adults.

1. The vast majority of bone mineralization in girls occurs by the middle of the second decade. 2. Premature bone demineralization occurs in women with hypothalamic dysfunction manifest as amenorrhea and oligomenorrhea, associated with athletics, dancing, and eating disorders. 3. In young women with amenorrhea associated with weight loss, BMD loss will be occurring soon after the amenorrhea develops. Treatment to prevent BMD loss or promote BMD accretion should begin soon, probably within 6 months after amenorrhea occurs. 4. Women who recover from anorexia nervosa at a young age (< 15 years of age) can have normal total body BMD, but regional (lumbar spine and femoral neck) BMD may remain low. The longer the anorexia nervosa persists, the less likely it is that the BMD will return to normal. Girls and women with anorexia nervosa need to be rehabilitated early in the disease to maximize BMD accretion. 5. Conjugated estrogen, in doses that improve bone mineralization in postmenopausal women and in combination with medroxyprogesterone, has not been shown to improve BMD in young women with hypothalamic amenorrhea. The role of orally administered medroxyprogesterone at a dose of 10 mg per day, 10 days per month, in improving BMD in teenage girls with hypothalamic amenorrhea or oligomenorrhea remains to be established. 6. Treatment with OCP may have a beneficial effect on BMD in young women with hypothalamic amenorrhea, but this has not been established in a double-masked, randomized, controlled trial. Doing a double-masked trial using OCP will be difficult because estrogen-deficient subjects treated with OCP will be likely to have menstrual bleeding, whereas those treated with placebo will not. In addition, the risk of pregnancy in a sexually active subject, who does not know whether she is receiving OCP, is too great for some subjects. 7. Osteoporosis is a major cause of morbidity and death. Peak bone mass is a major determinant of the risk of osteoporosis, and the second decade is the critical period of peak bone mass acquisition; thus providers of health care for adolescents need to understand the factors that affect bone mineralization during this period, and advise patients accordingly.