Skeletal Integrity Research Articles

Exogenous Vitamin D signaling alters skeletal patterning, differentiation, and tissue integration during limb regeneration in the axolotl

Urodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the “blueprint”, or pattern, of the regenerate is established and manipulated are areas of intense interest. Nutrient signaling plays an important role in pattern formation during regeneration. Retinoic acid signaling is the most characterized pathway during this process. Exogenous retinoic acid (RA) reprograms the pattern information in regenerating cells to a more posterior, ventral, and proximal identity. Vitamin D signaling shares several molecular similarities with RA and has been shown to alter pattern formation during zebrafish pectoral fin regeneration. To determine if exogenous Vitamin D signaling is capable of reprograming pattern in the axolotl limb blastema, we treated regenerating limbs with a potent Vitamin D agonist. Under the studied conditions, exogenous Vitamin D did not act in a manner similar to RA and failed to proximalize the pattern of the resulting regenerates. The Vitamin D treatment did result in several skeletal defects during regeneration, including carpal fusions along the A/P axis; failure to integrate the newly regenerated tissue with the existing tissue, formation of ectopic nodules of cartilage at the site of amputation, and altered bone morphology in uninjured skeletal tissue.

L-tyrosine supplementation does not ameliorate skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle \u03b1-actin nemaline myopathy

L-tyrosine supplementation may provide benefit to nemaline myopathy (NM) patients, however previous studies are inconclusive, with no elevation of L-tyrosine levels in blood or tissue reported. We evaluated the ability of L-tyrosine treatments to improve skeletal muscle function in all three published animal models of NM caused by dominant skeletal muscle α-actin (ACTA1) mutations. Highest safe L-tyrosine concentrations were determined for dosing water and feed of wildtype zebrafish and mice respectively. NM TgACTA1D286G-eGFP zebrafish treated with 10 μM L-tyrosine from 24 hours to 6 days post fertilization displayed no improvement in swimming distance. NM TgACTA1D286G mice consuming 2% L-tyrosine supplemented feed from preconception had significant elevations in free L-tyrosine levels in sera (57%) and quadriceps muscle (45%) when examined at 6–7 weeks old. However indicators of skeletal muscle integrity (voluntary exercise, bodyweight, rotarod performance) were not improved. Additionally no benefit on the mechanical properties, energy metabolism, or atrophy of skeletal muscles of 6–7 month old TgACTA1D286G and KIActa1H40Y mice eventuated from consuming a 2% L-tyrosine supplemented diet for 4 weeks. Therefore this study yields important information on aspects of the clinical utility of L-tyrosine for ACTA1 NM.

Fracture Risk Following Discontinuation of Teriparatide: A Review of the Literature.

To review and summarize studies on the changes in bone mineral density (BMD) and fracture risk following discontinuation of teriparatide therapy. A search of PubMed (1966-May 2016) and International Pharmaceutical Abstracts (1970-May 2016) was conducted using the Medical Subject Headings terms teriparatide, osteoporosis, and withholding treatment. Free text searches included drug holiday, discontinuation, and drug discontinuation. These searches yielded 79 articles. There were 7 articles reviewed that addressed the effects of teriparatide discontinuation on markers of overall bone health and fracture risk. Teriparatide is a recombinant human parathyroid hormone that is indicated for a lifetime maximum of 24 months in the United States for the treatment of osteoporosis in men and women at high fracture risk. There is inconsistent evidence regarding retained skeletal integrity resulting from increased bone resorption. Study analyses have shown that female patients seem to have more reduction in BMD upon teriparatide discontinuation. Several studies evaluating teriparatide discontinuation were follow-up studies with small patient populations, limiting the generalizability and statistical rigor associated with assessing these outcomes. In addition, the majority of patients were receiving bisphosphonate therapy, and the true effect of discontinuing teriparatide remains unknown. Independent patient risk factors should be taken into consideration when weighing the risk-vs.-benefit of initiating and discontinuing teriparatide therapy. Additional randomized control trials should be conducted to determine long-term effects of discontinuing teriparatide in the presence and absence of other bone-strengthening agents.

GFPT1 deficiency in muscle leads to myasthenia and myopathy in mice.

Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway which yields precursors required for protein and lipid glycosylation. Mutations in GFPT1 and other genes downstream of this pathway cause congenital myasthenic syndrome (CMS) characterized by fatigable muscle weakness owing to impaired neurotransmission. The precise pathomechanisms at the neuromuscular junction (NMJ) owing to a deficiency in GFPT1 is yet to be discovered. One of the challenges we face is the viability of Gfpt1−/− knockout mice. In this study, we use Cre/LoxP technology to generate a muscle-specific GFPT1 knockout mouse model, Gfpt1tm1d/tm1d, characteristic of the human CMS phenotype. Our data suggest a critical role for muscle derived GFPT1 in the development of the NMJ, neurotransmission, skeletal muscle integrity and highlight that a deficiency in skeletal muscle alone is sufficient to cause morphological postsynaptic NMJ changes that are accompanied by presynaptic alterations despite the conservation of neuronal GFPT1 expression. In addition to the conventional morphological NMJ changes and fatigable muscle weakness, Gfpt1tm1d/tm1d mice display a progressive myopathic phenotype with the presence of tubular aggregates in muscle, characteristic of the GFPT1-CMS phenotype. We further identify an upregulation of skeletal muscle proteins glypican-1, farnesyltransferase/geranylgeranyltransferase type-1 subunit α and muscle-specific kinase, which are known to be involved in the differentiation and maintenance of the NMJ. The Gfpt1tm1d/tm1d model allows for further investigation of pathophysiological consequences on genes and pathways downstream of GFPT1 likely to involve misglycosylation or hypoglycosylation of NMJs and muscle targets.

The Forgotten Variable: Effects of Sample Preparation and Storage on Geochemistry of Invertebrate Skeletal Carbonate

Standard sample preparation often includes cleaning, bleaching, preservation and storage techniques that may affect temperate invertebrate skeletal carbonate composition and integrity. Here we report on a series of interlinked studies and their key results. Rinsing with tap or deionised water has little detectable effect on sample composition and integrity. Bleaching with sodium hypochlorite, especially at low concentrations and for short times, results in no change in mineralogy or stable isotopes. High concentrations of bleach, and oxidation using H2O2, result in sample dissolution and the leaching of Mg from high-Mg samples. H2O2 has a significant effect on ∂18O stable isotope concentration. Chemical removal of organic material is often not necessary. Ultrasonication of samples results in loss of Mg and skeletal material generally, especially from high-Mg specimens. The combination of ultrasound with bleaching (a common shortcut) is even worse. Roasting of specimens to remove organic carbon causes dramatic changes in composition and cannot be recommended. New studies on the effect of storage in various preservatives and conditions are underway. In order to examine longer-term effects of storage, we have been mining museum collections. This collecting activity is ongoing and we would be glad to hear about material we have missed. Sample preparation and storage can have considerable effect on subsequent chemical investigations, and must form part of research planning, collection management, and sample labelling.

Structural stress response of segmented natural shells: a numerical case study on the clypeasteroid echinoid Echinocyamus pusillus.

The skeleton of Echinocyamus pusillus is considered as an exceptional model organism for structural strength and skeletal integrity within the echinoids as demonstrated by the absence of supportive collagenous fibres between single plates and the high preservation potential of their skeletons. The structural principles behind this remarkably stable, multi-plated, light-weight construction remain hardly explored. In this study, high-resolution X-ray micro-computed tomography, finite-element analysis and physical crushing tests are used to examine the structural mechanisms of this echinoid's skeleton. The virtual model of E. pusillus shows that the material is heterogeneously distributed with high material accumulations in the internal buttress system and at the plate boundaries. Finite-element analysis indicates that the heterogeneous material distribution has no effect on the skeleton's strength. This numerical approach also demonstrates that the internal buttress system is of high significance for the overall skeletal stability of this flattened echinoid. Results of the finite-element analyses with respect to the buttress importance were evaluated by physical crushing tests. These uniaxial compression experiments support the results of the simulation analysis. Additionally, the crushing tests demonstrate that organic tissues do not significantly contribute to the skeletal stability. The strength of the echinoid shell, hence, predominantly relies on the structural design.

Doxorubicin chemotherapy affects the intracellular and interstitial free amino acid pools in skeletal muscle.

Skeletal muscle (SM) health and integrity is dependent on the dynamic balance between protein synthesis and degradation, and central to this process is the availability of amino acids (AA) in the amino pool. While Doxorubicin (DOX) remains one of the most widely used chemotherapeutic agents for the treatment of solid and hematological malignancies, little is known of the effect of the drug on SM, particularly its effect on the availability of amino acids in the tissue. The purpose of this study was to examine the effect of DOX administration on vascular, interstitial and intracellular concentrations of AA in SM of the rat up to 8 days after the administration of a 1.5 or 4.5 mg/kg i.p. dose of DOX. In the plasma, total amino acids (TAA) were significantly increased compared to control where greater (P<0.05) concentrations were observed following the 1.5 mg/kg dose compared to the 4.5 mg/kg dose. Compared to control, the 1.5 mg/kg dose resulted in an increase (P<0.05) in interstitial TAA whereas the 4.5 mg/kg resulted in a sustained decrease (P<0.05). Intracellular TAA, essential amino acids (EAA) and branched-chain amino acids (BCAA) where significantly increased in each muscle group analyzed, following the 1.5 and 4.5 mg/kg doses compared to control. This study provides important insight into the amino acid response following DOX chemotherapy and presents a substantial foundation for future studies focused on reducing SM damage and recovery by targeting amino acid metabolism.

Cooperative electrogenic proton transport pathways in the plasma membrane of the proton-secreting osteoclast.

A proton is a ubiquitous signaling ion. Many transmembrane H+ transport pathways either maintain pH homeostasis or generate acidic compartments. The osteoclast is a bone-resorbing cell, which degrades bone tissues by secreting protons and lysosomal enzymes into the resorption pit. The plasma membrane facing bone tissue (ruffled border), generated partly by fusion of lysosomes, may mimic H+ flux mechanisms regulating acidic vesicles. We identified three electrogenic H+-fluxes in osteoclast plasma membranes-a vacuolar H+-ATPase (V-ATPase), a voltage-gated proton channel (Hv channel) and an acid-inducible H+-leak-whose electrophysiological profiles and regulation mechanisms differed. V-ATPase and Hv channel, both may have intracellular reservoirs, but the recruitment/internalization is regulated independently. V-ATPase mediates active H+ efflux, acidifying the resorption pit, while acid-inducible H+ leak, activated at an extracellular pH < 5.5, diminishes pit acidification, possibly to protect bone from excess degradation. The two-way H+ flux mechanisms in opposite directions may have advantages in fine regulation of pit pH. Hv channel mediates passive H+ efflux. Although its working ranges are limited, the amount of H+ extrusion is 100 times larger than those of the V-ATPase and may support reactive oxygen species production during osteoclastogenesis. Extracellular Ca2+, H+ and inorganic phosphate, which accumulate in the resorption pit, will either stimulate or inhibit these H+ fluxes. Skeletal integration is disrupted by too much or too less of bone resorption. Diversities in plasma membrane H+ flux pathways, which may co-operate or compete, are essential to adjust osteoclast functions in variable conditions.

The Time Point-Specific Effect of Beta-Adrenergic Blockade in Attenuating High Fat Diet-Induced Obesity and Bone Loss.

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12weeks, followed by another 12weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12weeks, followed by stratification into diet-based subgroups and another 12weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established.

Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Pituitary hormones have long been thought solely to regulate single targets. Challenging this paradigm, we discovered that both anterior and posterior pituitary hormones, including FSH, had other functions in physiology. We have shown that FSH regulates skeletal integrity, and, more recently, find that FSH inhibition reduces body fat and induces thermogenic adipose tissue. A polyclonal antibody raised against a short, receptor-binding epitope of FSHβ was found not only to rescue bone loss postovariectomy, but also to display marked antiobesity and probeiging actions. Questioning whether a single agent could be used to treat two medical conditions of public health importance--osteoporosis and obesity--we developed two further monoclonal antibodies, Hf2 and Mf4, against computationally defined receptor-binding epitopes of FSHβ. Hf2 has already been shown to reduce body weight and fat mass and cause beiging in mice on a high-fat diet. Here, we show that Hf2, which binds mouse Fsh in immunoprecipitation assays, also increases cortical thickness and trabecular bone volume, and microstructural parameters, in sham-operated and ovariectomized mice, noted on microcomputed tomography. This effect was largely recapitulated with Mf4, which inhibited bone resorption by osteoclasts and stimulated new bone formation by osteoblasts. These effects were exerted in the absence of alterations in serum estrogen in wild-type mice. We also reconfirm the existence of Fshrs in bone by documenting the specific binding of fluorescently labeled FSH, FSH-CH, in vivo. Our study provides the framework for the future development of an FSH-based therapeutic that could potentially target both bone and fat.

No evidence of damage to the soft tissue or skeletal integrity of mesophotic corals exposed to a 3D marine seismic survey

Scleractinian corals, primarily plate corals in families Agaricidae and Acroporidae, were monitored in situ before, during and after a 3D marine seismic survey. An initial four day seismic run, resulting in a maximum 24 h received sound exposure level (SEL24) of 204 dB re 1 μPa2·s and received 0-to-peak pressure (PK Pressure) of 226 dB re 1 μPa, had no detectable effect on soft tissues or skeletal integrity. Subsequently, a full marine seismic survey (Maxima 3D MSS), proceeded over two months and included seismic acquisition lines at 240 m spacing over the broader reef lagoon (South Scott Reef), generating maximum received SEL24 of 197 dB re 1 μPa2·s and received PK Pressure of 220 dB re 1 μPa at the coral monitoring sites. The analysis detected no effect of seismic activity measured as coral mortality, skeletal damage or visible signs of stress immediately after and up to four months following the 3D marine seismic survey.

Etlik Piliç ve Ebeveynlerinin Gelişimi

Et tipi tavukların seleksiyonu öncelikle büyüme hızına ve vücut kompozisyonunun geliştirilmesine odaklanmıştır. Büyüme ve üreme ile ilgili özellikler arasındaki negatif ilişki ıslah ve yetiştiricilik uygulamalarını zorlaştırmaktadır. Tavuk ıslahıyla ilgili çalışmalar yaklaşık 150 yıllık bir geçmişe dayanıyor olmasına karşın üretimdeki verim artışları son 75 yıllık dönemde sağlanabilmiştir. Damızlık hayvanlar seçilirken; iskelet yapısı, vücut konformasyonu ve kondisyonu, morbidite vb. fenotipik özellikler dikkate alınmaktadır. Yıllar içinde etlik ebeveyn düzeyinde kuluçkalık yumurta sayısı, yumurta ağırlığı ve kuluçka randımanı açısından ilerleme kaydedilmiştir. Et tipi tavuklar için, 20. yüzyılın ilk çeyreğinde kesim yaşına kadar günlük canlı ağırlık artışı ortalama 8 g ve yemden yararlanma oranı 5,0 iken 21. yüzyılın başında bu özellikler için sırasıyla 66 g ve 1,7 değerlerine ulaşmıştır. Etlik piliç üretiminde kullanılan genotiplerin canlı ağırlığındaki ve yemden yararlanma oranındaki iyileşmede etkili asıl faktör genetik çalışmalardır. Bu gelişmelerin yanında, etlik piliçlerin bağışıklık sistemi, iskelet sistemi bozuklukları, yaşama gücü ve damızlıklardaki üreme ile ilgili bazı olumsuzluklar ortaya çıkan sorunlardır.

Methylphenidate regulation of osteoclasts in a dose- and sex-dependent manner adversely affects skeletal mechanical integrity

Methylphenidate (MP) is the most prescribed psychostimulant for ADHD patients, with clinically demonstrated detrimental effects on bone quality, potentially leading to early onset osteoporosis and higher fracture risk. The underlying mechanism for the effects of MP on bone remains elusive. This study demonstrates that sex- and dose-dependent effects of MP on bone quality and quantity are mediated by osteoclast activity. Four-week-old male and female rats were treated with low and high dose MP for 13 weeks. Bone quality and quantity were analyzed using microCT, mechanical testing, histomorphometry, and TRAP staining. Male and female rat bone marrow-derived osteoclasts were treated in a dose-dependent manner (0–1000 ng/ml) and osteoclast activity was determined at days 5, 7, and 14 using TRAP staining, as well as a pit formation assay at day 18. Animal studies showed a dose- and a sex-dependent decrease in mechanical integrity in femora and increased TRAP staining in MP-treated rats. Primary cultures revealed that MP had direct dose- and sex-dependent effects on osteoclast activity, as seen by increased differentiation, activity, and resorption. This study demonstrates for the first time that osteoclasts are differentially regulated by MP in adolescent male and female rats, resulting in sex-dependent effects on the skeleton.

Rickets/Osteomalacia. Vitamin D action:Lessons from animal models.

Animal studies using mice model such as vitamin D deficiency and global and conditional VDR knock out(KO)mice have disclosed that the physiological role of vitamin D strongly depends on the calcium balance. Vitamin D stimulates active intestinal calcium transport mechanism, thereby maintains normocalcemia that has priority over skeletal integrity. Besides the biological significance of vitamin D extensively studied, its precise function in non-classical target needs further investigation.

Castration induces satellite cell activation that contributes to skeletal muscle maintenance

Sarcopenia, the age-related loss of skeletal muscle, is a side effect of androgen deprivation therapy (ADT) for prostate cancer patients. Resident stem cells of skeletal muscle, satellite cells (SCs), are an essential source of progenitors for the growth and regeneration of skeletal muscle. Decreased androgen signaling and deficits in the number and function of SCs are features of aging. Although androgen signaling is known to regulate skeletal muscle, the cellular basis for ADT-induced exacerbation of sarcopenia is unknown. Furthermore, the consequences of androgen deprivation on SC fate in adult skeletal muscle remain largely unexplored. We examined SC fate in an androgen-deprived environment using immunofluorescence and fluorescence-activated cell sorting (FACS) with SC-specific markers in young castrated mice. To study the effects of androgen deprivation on SC function and skeletal muscle regenerative capacity, young castrated mice were subjected to experimental regenerative paradigms. SC-derived-cell contributions to skeletal muscle maintenance were examined in castrated Pax7CreER/+; ROSA26mTmG/+ mice. SCs were depleted in Pax7CreER/+; ROSA26DTA/+ mice to ascertain the consequences of SC ablation in sham and castrated skeletal muscles. Confocal immunofluorescence analysis of neuromuscular junctions (NMJs), and assessment of skeletal muscle physiology, contractile properties, and integrity were conducted. Castration led to SC activation, however this did not result in a decline in SC function or skeletal muscle regenerative capacity. Surprisingly, castration induced SC-dependent maintenance of young skeletal muscle. The functional dependence of skeletal muscles on SCs in young castrated mice was demonstrated by an increase in SC-derived-cell fusion within skeletal muscle fibers. SC depletion was associated with further atrophy and functional decline, as well as the induction of partial innervation and the loss of NMJ-associated myonuclei in skeletal muscles from castrated mice. The maintenance of skeletal muscles in young castrated mice relies on the cellular contributions of SCs. Considering the well-described age-related decline in SCs, the results in this study highlight the need to devise strategies that promote SC maintenance and activity to attenuate or reverse the progression of sarcopenia in elderly androgen-deprived individuals.

D Hypovitaminosis in Syrian Type 2 Diabetes Mellitus Patients: Lack of Relationship with Glycemic Control

Vitamin D is a hormone related to skeletal integrity and many other health conditions. Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D3] and the risk of type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate plasma 25(OH)D3 levels in T2DM Syrian patients in Lattakia city, and to assess the relationship between 25(OH)D3 levels and glycemic control in addition to other variables (gender, age, duration of diabetes, BMI, smoking and fast blood glucose (FBG)). A total of 75 T2DM patients were included in the study. 25(OH)D3 was measured in serum samples using radioimmunoassay (RIA) method. Glycosylated hemoglobin A1c (HbA1c) was measured in whole blood samples using fast ion-exchange resin separation method. FBG was determined in whole blood samples by commercially available biochemical kits. The SPSS 17.0 program was used for the statistical analysis. Probability (P) value less than 0.05 was considered statistically significant. Vitamin D deficiency (25(OH)D3 ? 20 ng/ml) was seen in 55% of T2DM patients. Uncontrolled HbA1c was seen in 61.33% of T2DM patients. There was no relationship between serum 25(OH)D3 and HbA1c or FBG (P=0.989, P=0.611 respectively). The relationship of 25(OH)D3 with gender, age, duration of diabetes, smoking were not significant (P>0.05). However, there was a significant relationship between 25(OH)D3 and BMI (P=0.042). Our findings suggests that vitamin D deficiency is common in T2DM Syrian patients in Lattakia , and Its incidence decreases with BMI, even though its role in glycosylated hemoglobin could not be established.

The pattern of bone involvement, management, and outcomes in patients with nonsmall cell lung cancer: A retrospective study.

CONTEXT AND AIM:The skeleton is a frequent site for metastasis in patients with breast, lung, and prostate cancer. Bone metastasis compromises skeletal integrity leading to skeletal-related events (SREs). This study aims at estimating the prevalence of bone metastasis in lung cancer and describing types of bone involvement, management, outcomes, and overall survival.METHODS:We retrospectively reviewed the charts of 259 patients with nonsmall cell lung cancer who consulted the Department of Medical Oncology at our institution between January 2002 and December 2012. We documented their lung cancer characteristics, presence of skeletal metastases, management types, outcome parameters, and survival status.RESULTS:A total of 116 patients (58.6%) were diagnosed with bone metastasis. The most common site of metastasis was the spine. The most common SREs were bone pain (44%) and need for radiotherapy (25.9%). Patients with adenocarcinoma (P = 0.002) and concomitant liver metastasis (P = 0.013) tended to have more incidence of bone metastasis. Survival rates were (36%) at 1 year, and (3%) at 5 years. Metastasis to the bone did not impact patients' survival. Patients tended to have worse survival in the presence of concomitant bone and liver metastases (P = 0.012), older age (P = 0.024), lower limb metastasis (P = 0.014), hypercalcemia (P = 0.001), and not receiving calcium therapy (P = 0.011).CONCLUSION:Metastatic bone disease is considered a huge burden on patients, clinicians, and the society. The majority of bone metastasis patients will experience SREs. Most SREs predict poor prognosis. Supportive therapy to overcome the reasons for poor prognosis may improve patients' survival and quality of life.

Innovative layer genetics to handle global challenges in egg production

ABSTRACT1. In commercial layer breeding, extensive gene pools are tested and selected for market requirements which must be anticipated at least 5 years ahead. Field results confirm a continuous positive genetic trend in egg output and better feed efficiency which can be converted into land savings.2. Animal welfare and cage-free housing dominate future needs of the market. Nesting behaviour and minimal tendency to develop feather-pecking or cannibalism without beak treatment are key trait complexes. Stronger shells for longer production cycles without moulting have to be combined with better bones.3. No single big gene effect can be expected to control the multifactorial problem of feather-pecking. Adjusting the shape of the beak, with a heritability of .10–.25, can contribute to reducing the risk of severe cannibalism.4. For better skeletal integrity, the assessment of bone quality in pedigree birds housed in enriched cages is done by keel bone palpation or ultrasound measurement of the humerus. Both traits show similar heritabilities in the range of .15–.30 and can be included in a balanced selection approach for performance, quality and welfare traits.5. The combination of performance testing and genome-wide DNA marker analysis is a promising tool to generate more progress for a balanced performance and behaviour profile.

Marine Natural Products: New Avenue in Treatment of Osteoporosis

Bone metabolism is a physiological process that maintains the skeletal integrity and bone functions. Skeletal integrity is always balanced by two key cell types- bone resorbing osteoclasts and bone-forming osteoblasts. Imbalance between generation and function of osteoclasts and osteoblasts often leads to pathological conditions such as osteoporosis, osteopetrosis, Paget's disease. Osteoporosis is one of the most common age-related diseases characterized by decreased bone mineral density and microarchitectural deterioration. Current therapies are indeed effective in preventing bone loss but are also followed by side effects. Since many years, marine organisms have been considered as a good source of bioactive molecules or compounds with potential pharmaceutical properties. Marine natural products derived from various marine resources such as marine cyanobacteria, dinoflagellates, algae, sponges, soft corals, molluscs, fishes, and mangroves had shown profound effect on bone metabolism through inhibiting osteoclastogenesis and up-regulating osteoblastogenesis via modulating RANK/RANKL/OPG pathway. Amongst the pre-clinically investigated marine natural products for management of osteoporosis, very few are under phase I clinical trials. This review discusses the currently available pharmacological drugs and there major health concern in osteoporosis treatment. It further gives an insight into various marine resources and marine-derived bioactive products, depicting their mechanism of action, functional role and how these can be exploited for the treatment of osteoporosis.

Skeletal muscle performance and ageing.

The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co‐morbidity, and premature death. An important cause of physical limitations is the age‐related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation–contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing.