Absence of E2f1 Negates Pro-osteogenic Impacts of p21 Absence
In this study we aimed to investigate the interplay betweenp21 andE2f1 and determine if the pro-regenerative osteogenic effects observed with the loss ofp21 areE2f1 dependent. To accomplish this, we employed knockoutp21 andE2f1 mice and additionally generated ap21/E2f1 double knockout. These mice underwent burr-hole injuries to their proximal tibiae and healing was assessed over 7 days via microCT imaging. We found thatp21 andE2f1 play distinct roles in bone regeneration where the loss ofp21 increased trabecular bone formation and loss ofE2f1 increased cortical bone formation, yet loss ofE2f1 led to poorer bone repair ov...
Source: Calcified Tissue International - April 21, 2024 Category: Orthopaedics Source Type: research
Probiotics Supplements Improve the Sarcopenia-Related Quality of Life in Older Adults with Age-Related Muscle Decline
AbstractA pathological increase in intestinal leak is implicated in age-associated muscle loss, termed sarcopenia, and reduced sarcopenia-related quality-of-life (SarQoL). However, the potential therapies remain elusive. We investigated the effects of probiotic supplementation on sarcopenia and SarQoL in geriatric older adults. We randomized sarcopenic men into placebo (age = 71.4 ± 3.9 years,n = 63) and probiotic (age = 73 ± 4.1 years,n = 60) groups for 16 weeks. The probiotic used was one capsule daily of Vivomix 112 billion for 16 weeks. We measured sarcopenia parameters of handgrip strength (HGS) and s...
Source: Calcified Tissue International - April 20, 2024 Category: Orthopaedics Source Type: research
Metabolic and Skeletal Characterization of the KK/Ay Mouse Model —A Polygenic Mutation Model of Obese Type 2 Diabetes
AbstractType 2 diabetes (T2D) increases fracture incidence and fracture-related mortality rates (KK.Cg-Ay/J. The Jackson Laboratory; Available from:https://www.jax.org/strain/002468). While numerous mouse models for T2D exist, few effectively stimulate persistent hyperglycemia in both sexes, and even fewer are suitable for bone studies. Commonly used models like db/db and ob/ob have altered leptin pathways, confounding bone-related findings since leptin regulates bone properties (Fajardo et al. in Journal of Bone and Mineral Research 29(5): 1025 –1040, 2014). The Yellow Kuo Kondo (KK/Ay) mouse, a polygenic mutation model...
Source: Calcified Tissue International - April 20, 2024 Category: Orthopaedics Source Type: research
Extra-Skeletal Manifestations in Osteogenesis Imperfecta Mouse Models
AbstractOsteogenesis imperfecta (OI) is a rare heritable connective tissue disorder of skeletal fragility with an incidence of roughly 1:15,000. Approximately 85% of the pathogenic variants responsible for OI are in the type I collagen genes, COL1A1 and COL1A2, with the remaining pathogenic OI variants spanning at least 20 additional genetic loci that often involve type I collagen post-translational modification, folding, and intracellular transport as well as matrix incorporation and mineralization. In addition to being the most abundant collagen in the body, type I collagen is an important structural and extracellular ma...
Source: Calcified Tissue International - April 19, 2024 Category: Orthopaedics Source Type: research
Effects of Testosterone in Mediating the Relationship Between Daytime Napping and Osteoporosis in European Populations: A Mendelian Randomization Study
AbstractWe aimed to explore the causal effect of daytime napping on the risk of osteoporosis and the mediation role of testosterone in explaining this relationship. Summary data for Mendelian randomization (MR) analysis were obtained from the IEU OpenGWAS database. Univariable MR(UVMR) analysis and multiple sensitivity analyses were applied to explore the casual relationship between daytime napping and bone mineral density (BMD)/osteoporosis. We also conducted multivariable Mendelian randomization (MVMR) analysis to evaluate the correlation between testosterone-associated single-nucleotide variations and BMD/osteoporosis. ...
Source: Calcified Tissue International - April 18, 2024 Category: Orthopaedics Source Type: research
Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO)
This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammato ry bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach. (Source: Calcified Tissue International)
Source: Calcified Tissue International - April 16, 2024 Category: Orthopaedics Source Type: research
Development and Internal Validation of a Multivariable Prediction Model for Mortality After Hip Fracture with Machine Learning Techniques
AbstractIn order to estimate the likelihood of 1, 3, 6 and 12 month mortality in patients with hip fractures, we applied a variety of machine learning methods using readily available, preoperative data. We used prospectively collected data from a single university hospital in Copenhagen, Denmark for consecutive patients with hip fractures, aged 60 years and older, treated between September 2008 to September 2010 (n = 1186). Preoperative biochemical and anamnestic data were used as predictors and outcome was survival at 1, 3, 6 and 12 months after the fracture. After feature selection for each timepoint a stratified...
Source: Calcified Tissue International - April 16, 2024 Category: Orthopaedics Source Type: research
The PDE4 Inhibitors Roflumilast and Rolipram Rescue ADO2 Osteoclast Resorption Dysfunction
AbstractAutosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption caused by heterozygous missense mutations in the chloride channel 7 (CLCN7). Adenylate cyclase, which catalyzes the formation of cAMP, is critical for lysosomal acidification in osteoclasts. We found reduced cAMP levels in ADO2 osteoclasts compared to wild-type (WT) osteoclasts, leading us to examine whether regulating cAMP would improve ADO2 osteoclast activity. Although forskolin, a known activator of adenylate cyclase and cAMP levels, negatively affected osteoclast number, it led to an overall increase...
Source: Calcified Tissue International - April 1, 2024 Category: Orthopaedics Source Type: research
Differences in Vertebral Morphology and bone Mineral Density between Grade 1 Vertebral Fracture and Non-Fractured Participants in the Chinese Population
Conclusions:The grade 1 group had higher VSI and lower BMD than the non-fractured group, suggesting an association between the Grade 1 group and osteoporosis in individuals aged over 50 for women and over 60 for men. Different fracture types have significant variations in BMD among middle-aged people. The prevalence of grade 1 VFs exhibits an age-related increase in both genders, with opposite trends observed between older males and females. We suggested VSI can aid physicians in the diagnosis of grade 1 VFs. (Source: Calcified Tissue International)
Source: Calcified Tissue International - April 1, 2024 Category: Orthopaedics Source Type: research
Correction to: BMP2 Modified by the m6A Demethylation Enzyme ALKBH5 in the Ossification of the Ligamentum Flavum Through the AKT Signaling Pathway
(Source: Calcified Tissue International)
Source: Calcified Tissue International - April 1, 2024 Category: Orthopaedics Source Type: research
The Impact of Non-alcohol Fatty Liver Disease on Bone Mineral Density is Mediated by Sclerostin by Mendelian Randomization Study
AbstractNon-alcoholic fatty liver disease (NAFLD) has been found to be associated with osteoporosis (OP) in observational studies. However, the precise causal relationship between NAFLD and OP remains unclear. Here, we used Mendelian randomization (MR) to explore the causal relationship. We selected NAFLD-related single-nucleotide polymorphisms from a genome-wide meta-analysis (8434 cases and 434,770 controls) as instrumental variants. We used inverse variance weighted analysis for the primary MR analysis. Furthermore, we used similar methodologies in parallel investigations of other chronic liver diseases (CLDs). We perfo...
Source: Calcified Tissue International - March 31, 2024 Category: Orthopaedics Source Type: research
Medical Management for Fracture Prevention in Children with Osteogenesis Imperfecta
AbstractThere are no licensed treatments for children with osteogenesis imperfecta. Children currently receive off-label treatment with bisphosphonates, without any consistent approach to dose, drug or route of administration. Meta-analyses suggest that anti-fracture efficacy of such interventions is equivocal. New therapies are undergoing clinical trials, and it is likely that one or more will receive marketing authorisation within the next three to five years. The long-term outcome from such interventions will need to be studied carefully well beyond the period over which the clinical trials are conducted, and a consiste...
Source: Calcified Tissue International - March 29, 2024 Category: Orthopaedics Source Type: research
