Article
Endocrinology & Metabolism
Kyung-Eun Lim, Whitney A. Bullock, Daniel J. Horan, Bart O. Williams, Matthew L. Warman, Alexander G. Robling
Summary: In conclusion, unlike with the deletion of Lrp5 alone, the bone-selective late-stage co-deletion of Lrp5 and Lrp6 significantly impairs or completely nullifies the osteogenic action of Scl-mAb, and highlights a major role for both Lrp5 and Lrp6 in the mechanism of action for the bone-building effects of sclerostin antibody.
Article
Endocrinology & Metabolism
Roy B. Choi, April M. Hoggatt, Daniel J. Horan, Emily Z. Rogers, Gabriela G. Loots, Alexander G. Robling
Summary: The development of Wnt-based osteoanabolic agents has progressed rapidly in recent years, showing potent effects on bone homeostasis. Simultaneous inhibition of sclerostin and Dkk1 can enhance the effects in the cancellous bone. Further research reveals that Sostdc1 can be co-inhibited with sclerostin to improve cortical bone properties. Combined administration of sclerostin antibody and Sostdc1 antibody produces potentiation of cortical bone gain.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Deye Song, Guangxu He, Yu Shi, Jiangdong Ni, Fanxin Long
Summary: Wnt and Bmp proteins are known to interact in regulating bone development and homeostasis. Deletion of Bmpr1a results in suppressed Wnt genes in cortical bone and overexpression of Wnt7b can rescue periosteal bone growth in the absence of intact Bmp signaling, suggesting pharmacological activation of Wnt signaling can restore normal bone size.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Adi Cohen, Joseph Hostyk, Evan H. Baugh, Christie M. Buchovecky, Vimla S. Aggarwal, Robert R. Recker, Joan M. Lappe, David W. Dempster, Hua Zhou, Mafo Kamanda-Kosseh, Mariana Bucovsky, Julie Stubby, David B. Goldstein, Elizabeth Shane
Summary: The study identified likely pathogenic variants or relevant variants of uncertain significance in 8 out of 75 premenopausal women with idiopathic osteoporosis. These variants were consistent with diagnostic evaluations showing evidence of low bone formation rates or increased bone resorption. The majority of patients had no identifiable genetic etiology, indicating that further research is necessary to identify new genetic and non-genetic causes of early-onset osteoporosis.
Review
Nutrition & Dietetics
Alan A. Aragon, Kevin D. Tipton, Brad J. Schoenfeld
Summary: Age-related loss of muscle mass, strength, and performance, referred to as sarcopenia, has detrimental effects on human health. Intervention strategies combining exercise and nutrition have been proposed, but age-related blunting of muscle protein synthesis can hinder their efficacy. Multiple mechanisms, including reduced molecular signaling activity, insulin-mediated capillary recruitment, and increased splanchnic retention of amino acids, contribute to anabolic resistance. Obesity and sedentarism can worsen anabolic resistance through insulin resistance and inflammation. This review discusses key factors and proposes practical dietary interventions to prevent and mitigate anabolic resistance.
Article
Orthopedics
Alexandra K. O'Donohue, Aiken Dao, Justin D. Bobyn, Craig F. Munns, David G. Little, Aaron Schindeler
Summary: Osteogenesis imperfecta (OI), a genetic bone fragility disorder, can be treated with bone morphogenetic proteins (BMPs) and bisphosphonates (BPs). However, the use of BMPs as local agents for fracture healing in OI may be less effective, while the combination of BMP-2 and BPs shows considerable improvements in bone volume and polar moment of inertia. Therefore, caution should be taken when using BMP-2 alone in OI surgical settings, but the off-label administration of BPs may help overcome this limitation.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Review
Nutrition & Dietetics
Matthew D. Watson, Brett L. Cross, Gregory J. Grosicki
Summary: Globally, the population aged 65 and older is growing rapidly, facing issues such as changes in body composition, declines in cardiorespiratory fitness, and reductions in muscle size and function. Decreased muscle protein synthesis in response to anabolic stimuli plays a key role in the development of sarcopenia in aging individuals. Recent studies suggest a bidirectional gut-muscle axis affecting aging muscle health, with lifestyle habits potentially impacting changes in the microbiome.
Article
Cell & Tissue Engineering
Dezhi Zhao, Rui Hua, Manuel A. Riquelme, Hongyun Cheng, Teja Guda, Huiyun Xu, Sumin Gu, Jean X. Jiang
Summary: This study reveals the significant role of osteocytic integrin alpha 5 in the anabolic response of bone to mechanical loading. Deletion of integrin alpha 5 gene results in increased osteocyte apoptosis and reduced anabolic responses to tibial compression, including decreased osteoblasts and bone formation, and increased osteoclasts and bone resorption. This study suggests that integrin alpha 5 could be a potential therapeutic target for bone loss, especially in the elderly population with decreased mechanical sensitivity.
Article
Endocrinology & Metabolism
Jun Li, YanXia Ren, SiYuan Li, JiaJia Li
Summary: The study found that genetic polymorphism at the rs851056 locus is associated with bone mineral density in postmenopausal women with type 2 diabetes mellitus; individuals carrying the GG genotype may exhibit different biochemical markers and bone density; SOST protein expression levels are negatively correlated with bone mineral density.
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yuze Wang, Rulian Zhao, Erkuan Dai, Li Peng, Yunqi He, Mu Yang, Shujin Li
Summary: This study identified two novel missense variants in the LRP5 gene, expanding the variant spectrum for FEVR and providing valuable information for prenatal counseling and molecular diagnosis.
GENETIC TESTING AND MOLECULAR BIOMARKERS
(2022)
Article
Genetics & Heredity
Handong Dan, Dongdong Wang, Zixu Huang, Qianqian Shi, Miao Zheng, Yuanyuan Xiao, Zongming Song
Summary: This study investigated the potential disease-causing variants in 20 Chinese families with Familial exudative vitreoretinopathy (FEVR). The results revealed 14 variants in the NDP, FZD4, LRP5, and TSPAN12 genes among the families, expanding the spectrum of variants and providing insights for accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.
BMC MEDICAL GENOMICS
(2022)
Review
Sport Sciences
Philippe J. M. Pinckaers, Jorn Trommelen, Tim Snijders, Luc J. C. van Loon
Summary: There is a global trend towards plant-based diets, including a rise in plant-based protein consumption in sports nutrition. Plant-based proteins have lower anabolic properties compared to animal-based proteins, possibly due to differences in digestion and absorption kinetics, as well as amino acid composition. This discrepancy can potentially be addressed by consuming larger quantities, using blended proteins, or fortifying plant-based protein sources.
Review
Nutrition & Dietetics
Giacomo Garibotto, Michela Saio, Francesca Aimasso, Elisa Russo, Daniela Picciotto, Francesca Viazzi, Daniela Verzola, Alessandro Laudon, Pasquale Esposito, Giuliano Brunori
Summary: Dialysis-treated patients are often anabolic resistant, which can lead to muscle wasting and reduced physical performance. Strategies to overcome this resistance, including optimizing protein intake and physical activity, are essential for maintaining muscle mass and function in this patient population. Further research is needed to determine the optimal dose of proteins or amino acids to maximize muscle protein synthesis in dialysis patients.
FRONTIERS IN NUTRITION
(2021)
Article
Medicine, Research & Experimental
Daniely Messias Costa, Joao da Cruz- Filho, Alan Bruno Silva Vasconcelos, Joao Victor Gomes- Santos, Luis Carlos Reis, Waldecy de Lucca Jr, Enilton Aparecido Camargo, Sandra Lauton- Santos, Neusa Maria Zanon, Isis do Carmo Kettelhut, Luiz Carlos Navegantes, Andre de Souza Mecawi, Daniel Badaue Passos, Danilo Lustrino
Summary: The study found that oxytocin (OT) directly inhibits proteolytic activities in rat oxidative skeletal muscle by activating the Akt/FoxO signaling pathway, suppressing atrogene expression, and promoting muscle mass gain without affecting protein synthesis.
Article
Biochemistry & Molecular Biology
Niloofar Shekoohi, Miryam Amigo-Benavent, Guilherme Wesley Peixoto da Fonseca, Padraigin A. Harnedy-Rothwell, Richard J. FitzGerald, Brian P. Carson
Summary: Blue whiting protein hydrolysates have potential anabolic effects on muscle growth and protein synthesis, but the impact varies among different hydrolysates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Public, Environmental & Occupational Health
Ciarrah-Jane Barry, David Carslake, Kaitlin H. Wade, Eleanor Sanderson, George Davey Smith
Summary: This study applied and evaluated two intergenerational instrumental variable methods to estimate the average causal effect of BMI on mortality. The results suggested that higher BMI increased mortality, but caution is required in interpreting the exact values as causal.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Hannah M. Sallis, Tom Palmer, Kate Tilling, George Davey Smith, Marcus R. Munafo
Summary: This study used Mendelian randomization and reverse MR to investigate the confounding effect of reverse causality in the association between alcohol consumption and educational attainment, physical and mental health. The findings suggest that observed beneficial effects of alcohol consumption may be attributed to confounding by reverse causation.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jean-Baptiste Pingault, Wikus Barkhuizen, Biyao Wang, Laurie J. Hannigan, Espen Moen Eilertsen, Elizabeth Corfield, Ole A. Andreassen, Helga Ask, Martin Tesli, Ragna Bugge Askeland, George Davey Smith, Camilla Stoltenberg, Neil M. Davies, Ted Reichborn-Kjennerud, Eivind Ystrom, Alexandra Havdahl
Summary: This study explores the mechanisms underlying the intergenerational transmission of risk for ADHD traits. The results suggest that genetic factors play a major role in this transmission, rather than environmental influences from parents. The findings emphasize the importance of considering genetic transmission in understanding the development of ADHD.
MOLECULAR PSYCHIATRY
(2023)
Article
Biology
Nathan J. Cheetham, Milla Kibble, Andrew Wong, Richard J. Silverwood, Anika Knuppel, Dylan M. Williams, Olivia K. L. Hamilton, Paul H. Lee, Charis Bridger Staatz, Giorgio Di Gessa, Jingmin Zhu, Srinivasa Vittal Katikireddi, George B. Ploubidis, Ellen J. Thompson, Ruth C. E. Bowyer, Xinyuan Zhang, Golboo Abbasian, Maria Paz Garcia, Deborah Hart, Jeffrey Seow, Carl Graham, Neophytos Kouphou, Sam Acors, Michael H. Malim, Ruth E. Mitchell, Kate Northstone, Daniel Major-Smith, Sarah Matthews, Thomas Breeze, Michael Crawford, Lynn Molloy, Alex S. F. Kwong, Katie Doores, Nishi Chaturvedi, Emma L. Duncan, Nicholas J. Timpson, Claire J. Steves
Summary: This study found that antibody levels against SARS-CoV-2 can be used to evaluate immune responses and predict the risk of future infection. Higher antibody levels are associated with increased protection against future infections. The study also demonstrated that a third dose of the vaccine can increase antibody levels and reduce disparities compared to earlier vaccinations.
Article
Rheumatology
Benjamin G. Faber, Monika Frysz, April E. Hartley, Raja Ebsim, Cindy G. Boer, Fiona R. Saunders, Jennifer S. Gregory, Richard M. Aspden, Nicholas C. Harvey, Lorraine Southam, William Giles, Christine L. Le Maitre, J. Mark Wilkinson, Joyce B. J. van Meurs, Eleftheria Zeggini, Timothy Cootes, Claudia Lindner, John P. Kemp, George Davey Smith, Jonathan H. Tobias
Summary: This study examined the genetic architecture of cam morphology using the alpha angle (AA) as a measure and found a bidirectional relationship between AA and hip osteoarthritis (OA). The results suggest that a genetic predisposition to hip OA contributes to the relationship between hip OA and cam morphology, indicating the importance of genetic factors in the development of these conditions.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Laurence J. Howe, Humaira Rasheed, Paul R. Jones, Dorret Boomsma, David M. Evans, Alexandros Giannelis, Caroline Hayward, John L. Hopper, Amanda Hughes, Hannu Lahtinen, Shuai Li, Penelope A. Lind, Nicholas G. Martin, Pekka Martikainen, Sarah E. Medland, Tim T. Morris, Michel G. Nivard, Jean-Baptiste Pingault, Karri Silventoinen, Jennifer A. Smith, Emily A. Willoughby, James F. Wilson, Bjorn Olav Asvold, Oyvind E. Naess, George Davey Smith, Jaakko Kaprio, Ben Brumpton, Neil M. Davies
Summary: Previous Mendelian randomization (MR) studies suggest that educational attainment has beneficial effects on adult health outcomes. However, these estimates may be biased due to population stratification, assortative mating, and indirect genetic effects. Using both population and within-sibship MR approaches, this study provides evidence that genetic liability to educational attainment is associated with decreased BMI, cigarette smoking, and SBP, and potentially with mortality.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Stefan Stender, George Davey Smith, Tom G. Richardson
Summary: The study aimed to determine whether genetic risk factors for fatty liver disease (FLD) begin to exert their deleterious effects during childhood, adolescence, and early adulthood. The results showed that genetic risk factors were associated with elevated liver enzymes starting from childhood and their effects amplified with increasing age.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Hannah M. Sallis, Robyn E. Wootton, George Davey Smith, Marcus R. Munafo
Summary: This study used a proxy gene-by-environment Mendelian randomization approach to investigate the causal effect of maternal smoking during pregnancy on offspring mental health. The results suggest that the effect of maternal smoking on offspring schizophrenia is dependent on offspring smoking status. However, there is no clear evidence of an association between maternal smoking heaviness and offspring depression.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Multidisciplinary Sciences
Laura A. Magee, Erika Molteni, Vicky Bowyer, Jeffrey N. Bone, Harriet Boulding, Asma Khalil, Hiten D. Mistry, Lucilla Poston, Sergio A. Silverio, Ingrid Wolfe, Emma L. Duncan, Peter von Dadelszen
Summary: Among women of reproductive age, older age, White ethnicity, and being in the least-deprived index of multiple deprivation are independently associated with higher vaccine uptake. Ethnicity has the strongest influence, while multiple deprivation has the weakest. These findings are crucial for informing future vaccination policies and public messaging.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Mark Gormley, Tom Dudding, Steven J. Thomas, Jessica Tyrrell, Andrew R. Ness, Miranda Pring, Danny Legge, George Davey Smith, Rebecca C. Richmond, Emma E. Vincent, Caroline Bull, Belinda Nicolau
Summary: A recent study suggests that smoking, alcohol consumption, and obesity are important modifiable lifestyle factors contributing to cancer. However, further investigation is needed to identify other potential risk factors for head and neck cancer, especially in light of the declining smoking rates. The study conducted Mendelian randomization using genetic variants associated with adiposity, diabetes, and hypertension to explore their causal effects on oral and oropharyngeal cancer risk. The findings suggested limited evidence of a causal relationship between body mass index, diabetes, hypertension, and the risk of head and neck cancer.
Article
Geriatrics & Gerontology
Antony Johansen, Opinder Sahota, Frances Dockery, Alison J. Black, Alasdair M. J. Maclullich, M. Kassim Javaid, Emer Ahern, Celia L. Gregson
Summary: Currently, in the UK and Ireland, the majority of patients with hip fracture do not receive bone protection medication, despite the evidence showing that intravenous zoledronate significantly reduces refracture risk. This paper discusses the clinical uncertainties, doubts over the evidence base, and practical concerns that contribute to the variability in the use of intravenous zoledronate following a hip fracture. It provides expert consensus guidance to assist healthcare professionals in establishing local protocols to deliver this highly clinically and cost-effective treatment to reduce costly re-fractures in this vulnerable population.
Article
Genetics & Heredity
Ana Luiza Arruda, April Hartley, Georgia Katsoula, George Davey Smith, Andrew P. Morris, Eleftheria Zeggini
Summary: Multimorbidity is a growing public health challenge and understanding its genetic basis is crucial. This study focuses on the comorbidity between type 2 diabetes and osteoarthritis and identifies genetic correlation and association-signal colocalization between the two diseases. The integration of multi-omics and functional information reveals high-confidence effector genes and enrichment for lipid metabolism and skeletal formation pathways. Causal inference analysis shows complex effects of tissue-specific gene expression on comorbidity outcomes, providing insights into the biological basis of the disease co-occurrence.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Medicine, General & Internal
Maria K. Sobczyk, Jie Zheng, George Davey Smith, Tom R. Gaunt
Summary: We conclude that careful triangulation of MR with RCT evidence should involve consideration of similarity of phenotypes across study designs, intervention intensity and duration, study population demography and health status, comparator group, intervention goal and quality of evidence.
Article
Medicine, General & Internal
Benjamin G. Faber, Monika Frysz, Cindy G. Boer, Daniel S. Evans, Raja Ebsim, Kaitlyn A. Flynn, Mischa Lundberg, Lorraine Southam, April Hartley, Fiona R. Saunders, Claudia Lindner, Jennifer S. Gregory, Richard M. Aspden, Nancy E. Lane, Nicholas C. Harvey, David M. Evans, Eleftheria Zeggini, George Davey Smith, Timothy Cootes, Joyce Van Meurs
Summary: In this study, a genome-wide association study (GWAS) was conducted to identify genetic determinants of hip minimum joint space width (mJSW) and their association with hip osteoarthritis (HOA). The results revealed two distinct causal mechanisms, one group of mJSW loci reduce HOA risk and may be potential targets for chondroprotective therapies, while another group of mJSW loci increase HOA risk and contribute to HOA risk via a growth-related mechanism.
Article
Biology
Carolina Medina-Gomez, Benjamin H. Mullin, Alessandra Chesi, Vid Prijatelj, John P. Kemp, Chen Shochat-Carvalho, Katerina Trajanoska, Carol Wang, Raimo Joro, Tavia E. Evans, Katharina E. Schraut, Ruifang Li-Gao, Tarunveer S. Ahluwalia, M. Carola Zillikens, Kun Zhu, Dennis O. Mook-Kanamori, Daniel S. Evans, Maria Nethander, Maria J. Knol, Gudmar Thorleifsson, Ivana Prokic, Babette Zemel, Linda Broer, Fiona E. McGuigan, Natasja M. van Schoor, Sjur Reppe, Mikolaj A. Pawlak, Stuart H. Ralston, Nathalie van der Velde, Mattias Lorentzon, Kari Stefansson, Hieab H. H. Adams, Scott G. Wilson, M. Arfan Ikram, John P. Walsh, Timo A. Lakka, Kaare M. Gautvik, James F. Wilson, Eric S. Orwoll, Cornelia M. van Duijn, Klaus Bonnelykke, Andre G. Uitterlinden, Unnur Styrkarsdottir, Kristina E. Akesson, Timothy D. Spector, Jonathan H. Tobias, Claes Ohlsson, Janine F. Felix, Hans Bisgaard, Struan F. A. Grant, J. Brent Richards, David M. Evans, Bram van der Eerden, Jeroen van de Peppel, Cheryl Ackert-Bicknell, David Karasik, Erika Kague, Fernando Rivadeneira
Summary: Skull bone mineral density (SK-BMD) is a suitable trait for studying bone biology, particularly related to intramembranous ossification. A genome-wide association meta-analysis identified 59 loci associated with SK-BMD, which collectively explained 12.5% of the variance in the trait. These loci are involved in skeletal development and osteoporosis, and four of them are related to intramembranous ossification and craniofacial abnormalities.
COMMUNICATIONS BIOLOGY
(2023)