Metabolic Bone Disease Research Articles

Cystinosis metabolic bone disease: inflammatory profile in human peripheral blood mononuclear cells and derived osteoclasts.

There is an inflammatory profile in PBMCs and osteoclastic lineage in cells obtained from cystinotic patients. CXCR3 and MCP-1 stimulate migration and activation of macrophages, that may explain the previously reported local increased osteoclastogenesis. The osteoclastic overexpression of IL-1 Receptor is a relevant observation in the field since blocking Il-1β signaling has recently been proposed as a novel therapeutic approach to improve muscular wasting in this orphan disease. • Cystinosis metabolic bone disease (CMBD), an emerging concept with unclear underlying mechanisms, induces bone pains, fractures and deformations in patients with cystinosis. • Blocking Il-1β signaling may be a novel therapeutic approach to improve muscular wasting in cystinosis. • There is an inflammatory profile in PBMCs and osteoclastic lineage in cells obtained from cystinotic patients, with an over-expression of IL-1 Receptor in osteoclasts. • We provide another experimental rationale to propose targeted anti-inflammatory therapies in cystinotic patients with severe bone disease.

ZFP36, an RNA-binding protein promotes hBMSCs osteogenic differentiation via binding with JUN.

Osteoporosis (OP) is a metabolic bone disease characterized by progressive decline of bone mass and bone quality, leading to bone fragility and an increased risk of fracture. The osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is crucial to maintain the balance of osteoblast and osteoclast. Bioinformatics prediction indicates that ZFP36 ring finger protein (ZFP36), an RNA-binding protein, is a potential target of OP. Herein, we sought to probe the regulatory role and mechanisms of ZFP36 in the progression of OP. Overexpression of ZFP36 enhanced osteoblast viability, differentiation and mineralization of human BMSCs (hBMSCs). RNA immunoprecipitation qPCR (RIP-qPCR) assays demonstrated that ZFP36 could inhibit the translation of JUN, which was also verified with dual luciferase reporter gene assay. Furthermore, administration with T-5224, a transcription factor c-Fos/activator protein (AP)-1 inhibitor, which specifically inhibits the DNA binding activity of c-Fos/JUN, abolished the effect of ZFP36 knockdown on the behaviors of hBMSCs, suggesting that ZFP36 might promotes osteogenic differentiation through regulating JUN. These findings provide insights into the progression and a potential therapeutic target of OP.

Evaluation of the Awareness and Knowledge Levels of Dentists Regarding Bisphosphonates and Bisphosphonate-Related Jaw Necrosis

Bisphosphonates are used in the treatment of osteoporosis, bone metastases, and metabolic bone diseases. Long-term use of bisphosphonates increases the risk of osteonecrosis in patients undergoing dental surgery. This study aimed to evaluate dentists’ knowledge about bisphosphonates and bisphosphonate-related osteonecrosis of the jaw (BRONJ) and their treatment approaches in patients using oral and intravenous bisphosphonates. In this study, a 25-question questionnaire was applied to dentists working in different institutions regarding their knowledge and experience about bisphosphonates and BRONJ, and treatment approaches for different surgical procedures in patients using bisphosphonates. The obtained data were statistically analyzed and evaluated. In total, 90.5% of the dentists identified osteoporosis, 79.8% identified bone metastases, 52.4% identified osteitis deformans, and 39.3% identified multiple myeloma as conditions in which bisphosphonates are used, thus answering correctly in a significant proportion. When participants were asked about treatment options according to the stages of BRONJ, participation in the “I’m not sure” option increased as the stages progressed, indicating that dentists were not sufficiently familiar with the treatments for different stages of BRONJ. In total, 88.5% of the participants stated that when they see an exposed bone area in patients they examine, they consider bisphosphonate use as a possible cause. There was a statistically significant difference between dentists with and without prior BRONJ experience regarding their ages (P=0.039) and years of practice (P=0.001). There was a statistically significant difference between dentists with and without BRONJ experience regarding whether they inquired about bisphosphonate use (P=0.001). It was found that dentists have serious deficiencies in knowledge regarding bisphosphonates, their side effects, and treatment approaches for patients using bisphosphonates. Increasing dentists’ knowledge and awareness of this issue would help reduce the risk of developing BRONJ.

Correlation Between Vitamin D Deficiency and Calcium, Phosphorus, Alkaline Phosphatase in Preterm Libyan Infants: Case-Control study

Vitamin D plays a vital role in regulating calcium and phosphorus levels and in bone mineralization. Vitamin D deficiency is a widespread issue contributing to metabolic bone disease in preterm infants. This study aimed to evaluate the biochemical parameters associated with varying levels of vitamin D deficiency. Serum samples were collected from preterm infants at the Neonatal Intensive Care Unit of Althawra Hospital Center, Al Beyda, Libya, from Feb-July 2019. The study included two groups: 62 preterm infants and a control group of 34 full-term infants. Serum levels of calcium, phosphorus, alkaline phosphatase, and 25OH-Vitamin D were measured using enzyme immunoassays and standard method. The study involved 62 preterm neonates, with a median gestational age of 32 weeks (range 28-36) and median birth weight of 1960 gm (range 900-2800 gm). The median levels recorded were calcium at 8.7 mg/dl (p=0.000), phosphorus at 4.1 mg/dl (p=0.584), ALP at 458 U/L (p=0.008), and vitamin D at 13.6 ng/ml. The prevalence of varying degrees of vitamin D deficiency was noted: very severe (9.7% < 5 ng/ml), severe (19.4% 5-10 ng/ml), and overall deficiency (45% 10-20 ng/ml), and suboptimal (25.8% 20-30 ng/ml). Comparing preterm infants to the control group revealed statistically significant differences across all parameters (Vitamin D p=0.000, Ca p=0.007, PO4 p=0.036, and ALP p=0.000). All preterm infants exhibited inadequate vitamin D levels, and there was an inverse relationship between the biochemical parameters and vitamin D deficiency. Notably, the elevated ALP level could serve as a crucial marker for diagnosing vitamin D deficiency in clinical settings.

Suppressive Effects of Geoje Raspberry (Rubus tozawae Nakai ex J.Y. Yang) on Post-Menopausal Osteoporosis via Its Osteogenic Activity on Osteoblast Differentiation

Background: Osteoporosis is a metabolic bone disease with a high mortality rate due to non-traumatic fractures. The risk of osteoporosis is increasing globally due to an increasing aging population. Current therapies are limited to delaying disease progression. Recently, the need to discover foods with osteogenic activity for the prevention and treatment of osteoporosis has been emphasized. We focused on bone formation via osteoblast differentiation, considering bone formation and resorption during bone homeostasis. Rubus tozawae Nakai ex J. Y. Yang (RL, Geoje raspberry) is a deciduous subshrub that has been traditionally eaten for its fruit. Methods and Results: We identified the third subfraction of n-hexane fraction (RL-Hex-NF3) of RL, an endemic Korean plant with osteogenic activity, which increased bone density in ovariectomized mice, a representative animal model of osteoporosis, via the depletion of female hormones, which resulted from the increase in the osteoblast population. RL-Hex-NF3 induced osteoblast differentiation and the expression of osteogenic markers in MC3T3-E1 pre-osteoblasts. Seven compounds were identified from RL-Hex-NF3 using NMR spectroscopy. Of these, three compounds, namely, 3β-hydroxy-18α,19α-urs-20-en-28-oic acid, betulinic acid, and (1S,6R,7S)-muurola-4,10(14)-diene-15-ol, showed strong osteogenic activity. Conclusions: RL-Hex-NF3 and its compounds suppress bone loss via their osteogenic properties, suggesting that they could be a potent candidate to treat osteoporosis.

Rigid intramedullary nailing of lower limb segments in children and adolescents with metabolic bone disease.

Children and adolescents with metabolic bone disease present to the orthopedic surgeon with pain, fractures (which may be impending), and deformity. Different modalities of orthopedic management are available. Scant literature exists on the use of rigid intramedullary nailing in this population. This study sought to evaluate the utilization of this treatment modality in the pediatric cohort, focusing on indications, techniques, and outcomes of the procedures. A retrospective review was performed over an 11-year period at a single tertiary pediatric institution in the UK. Medical records and radiographs were reviewed. Preoperative surgical and medical management, time to bony union, and complications were specifically ascertained. Twenty-seven patients (63 lower limb segments) had rigid intramedullary nailing over the specified period. The majority of patients had an underlying diagnosis of osteogenesis imperfecta or fibrous dysplasia (including McCune Albright Syndrome). Surgical indications included acute fractures, prophylactic stabilization, previous nonunion and malunions, deformity correction, and limb lengthening. All fractures healed and deformity correction was successful. In one patient, delayed union occurred after deformity correction and was successfully treated with dynamization. Fractures healed faster than corrective osteotomies. Complications included implant prominence, cortical penetrance, and screw loosening. Nonunion occurred with limb lengthening in one patient. Rigid intramedullary nailing is a safe and effective method of treatment for lower limb fractures and deformities in children and adolescents. This technique is, therefore, recommended for patients with metabolic bone disease. However, care must be taken in preoperative surgical planning and a multidisciplinary approach should be utilized.

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

Bone Mineral Density and First Line Imaging with [18F]fluorocholine PET/CT in Normocalcemic and Hypercalcemic Primary Hyperparathyroidism: Results from a Single Center

Objectives: Primary hyperparathyroidism (PHPT) is associated with normal or elevated calcium levels and affects bone mineral density. The proportion of cases predisposed to metabolic bone disease is unknown in patients with PHPT. The aim of this study was to assess bone mineral density and bone quality in patients with normo- or hypercalcemic primary hyperparathyroidism undergoing baseline parathyroid gland assessment with [18F]fluorocholine PET/CT imaging. Methods: A total of 140 consecutive patients were enrolled in this observational study. All patients with normo- or hypercalcemic primary hyperparathyroidism underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS). [18F]fluorocholine PET/CT was performed in all patients for the detection and localization of parathyroid adenoma. Hyper- and normocalcemic patients were compared with regard to the proportion of osteoporosis and osteopenia, T-Score, TBS, serum calcium, phosphorus and parathyroid hormone levels, the maximum standardized uptake value (SUVmax) in PET/CT imaging, and laboratory results. Results: The majority of patients was female (88.57%) and had a pathologic bone mineral density (52.86%). Overall, 33 patients had osteoporosis and 41 osteopenia. The mean lumbar T-Score was −1.48 (SD 1.37) and the T-Score of the femoral neck was −1.21 (SD 0.92). Mean TBS was also decreased (−2.13). No difference was found between normo- or hypercalcemic patients regarding bone metabolism and imaging parameters. Conclusions: More than half of patients with normo- or hypercalcemic PHPT showed abnormal BMD. First-line [18F]fluorocholine PET/CT identified parathyroid adenoma in a high proportion of patients, even in patients with normocalcemic PHPT. The early evaluation of metabolic bone disease seems desirable in clinical management of females with PHPT.

Diagnostic and New Therapeutic Approaches to Two Challenging Pediatric Metabolic Bone Disorders: Hypophosphatasia and X-linked Hypophosphatemic Rickets.

The diagnosis and management of metabolic bone disease among children can be challenging. This difficulty could be due to many factors, including limited awareness of these rare conditions, the complex pathophysiology of calcium and phosphate homeostasis, the overlapping phenotype with more common disorders (such as rickets), and the lack of specific treatments for these rare disorders. As a result, affected individuals could experience delayed diagnosis or misdiagnosis, leading to improper management. In this review, we describe the challenges facing diagnostic and therapeutic approaches to two metabolic bone disorders (MBD) among children: hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). We focus on explaining the pathophysiological processes that conceptually underpin novel therapeutic approaches, as well as these conditions' clinical or radiological similarity to nutritional rickets. Particularly in areas with limited sun exposure and among patients not supplementing vitamin D, nutritional rickets are still more common than HPP and XLH, and pediatricians and primary physicians frequently encounter this disorder in their practices. More recently, our understanding of these disorders has significantly improved, leading to the development of novel therapies. Asfotas alfa, a recombinant, human- tissue, nonspecific alkaline phosphatase, improved the survival of patients with HPP. Burosumab, a human monoclonal anti-FGF23 antibody, was recently approved as a specific therapy for XLH. We also highlight the current evidence on these two specific therapies' safety and effectiveness, though long-term data are still needed. Both HPP and XLH are multisystemic disorders that should be managed by multidisciplinary teams. Finally, recognizing these conditions in early stages will enable affected children and young adults to benefit from newly introduced, specific therapies.

A Multidisciplinary and a Comprehensive Approach to Reducing Fragility Fractures in Preterm Infants.

With advances in neonatal care, bone fractures prior to discharge from the hospital in preterm infants receiving contemporary neonatal care, are rare. Nevertheless, such fractures do occur in very low birth weight and extremely low birth weight infants who go on to develop metabolic bone disease of prematurity (MBDP), with or without secondary hyperparathyroidism. MBDP is a multifactorial disorder arising from the disruption of bone mass accrual due to premature birth, postnatal immobilisation, and loss of placental oestrogen resulting in bone loss, inadequate provision of bone minerals from enteral and parenteral nutrition, and medications that leach out bone minerals from the skeleton. All of these factors lead to skeletal demineralisation and a decrease in bone strength and an increased risk of fractures of the long bones and ribs. Secondary hyperparathyroidism resulting from phosphate supplements, or enteral/parenteral feeds with a calcium-tophosphate ratio of < 1.3:1.0 leads to subperiosteal bone resorption, cortical thinning, and further skeletal weakening. Such fractures may occur from routine handling and procedures such as cannulation. Most fractures are asymptomatic and often come to light incidentally on radiographs performed for other indications. In 2015, we instituted a comprehensive and multidisciplinary Neonatal Bone Health Programme (NBHP), the purpose of which was to reduce fragility fractures in highrisk neonates, by optimising enteral and parenteral nutrition, including maintaining calcium-tophosphate ratio ≥1.3:1, milligram to milligram, biochemical monitoring of MBDP, safe-handling of at-risk neonates, without compromising passive physiotherapy and skin-to-skin contact with parents. The at-risk infants in the programme had radiographs of the torso and limbs at 4 weeks and after 8 weeks from enrolment into the program or before discharge. Following the introduction of the NBHP, the bone fracture incidence reduced from 12.5% to zero over an 18-month period.

Morin Improves the Bone Histomorphology and Biochemical Markers in an Animal Model of Ovariectomy‐Induced Osteoporosis by Suppressing Autophagy and Apoptosis

ABSTRACTOsteoporosis (OP) is the most prevalent metabolic bone disease and an important postmenopausal consequence. This study aimed to investigate the effects of morin, a flavonoid with beneficial properties, on ovariectomy‐induced OP. Animals were ovariectomized (OVX) and treated with different doses of morin (15, 30, and 45 mg/kg/day) or estradiol (10 μg/kg/day) for 10 weeks by gavage. Then bone histo‐stereology, bone‐related biochemical indicators, and gene and protein levels of autophagy and apoptosis‐related markers were analyzed. In comparison to controls, OVX significantly decreased the number of osteoblasts (5.78 × 106 vs. 1.66 × 106) and osteocytes (32.55 × 106 vs. 11.92 × 106), whereas increasing the number of osteoclasts (83.38 × 103 vs. 392.1 × 103). Moreover, OVX caused a remarkable decrease in bone structures and Ca, P, and estradiol levels while increasing ALP and OC (p &lt; 0.001). The administration of 45 mg/kg/day morin restored the effects of OP on bone histomorphology and biochemical markers (p &lt; 0.05). Further studies revealed that morin caused a 7.1% and 36.6% decrease in the bone level of LC3 and BECN1 proteins, respectively, compared to the OVX group. Also, morin caused a significant decrease of 47.4% in the CASP3 level and a significant increase of 23.6% in the BCL‐2 level compared to OVX animals (p &lt; 0.001). The present findings showed that morin is potentially able to improve the bone‐related histomorphological and biochemical changes caused by osteoporosis, which is probably attributed to the suppression of apoptosis‐ and autophagy‐caused cell death.

A Study on the Rationality of Baicalein in the Treatment of Osteoporosis: A Narrative Review.

Baicalein (BN) is an active ingredient naturally present in Chinese herbs, such as Scutellaria baicalein, Coptis chinensis, and Dendrobium officinale. It has a variety of pharmacological activities, including antioxidant, anti-inflammatory and antibacterial effects. Therefore, Baicalein (BN) is widely used in the field of medicine and is considered a potential natural medicine. Osteoporosis (OP) is a bone metabolic disease characterized by decreased bone mineral density and bone structure destruction, which is mainly caused by decreased bone formation and increased bone resorption. With the continuous development of molecular biology, the signaling pathways and gene targets of bone metabolism are also expanding. Recent studies have shown that baicalein may affect the function of osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells through MAPK/ERK and MAPKs/NF-κB signaling pathways, so as to have a therapeutic effect on OP. However, the specific mechanism of baicalein in the treatment of OP is still unclear. This article reviews the literature, analyzes and summarizes the mechanism of action of baicalein, and discusses its potential in the prevention and treatment of OP, so as to provide a basis for the clinical application of baicalein.

Osteoporosis in Systemic Mastocytosis: A Scoping Review

Background: Mastocytosis (MS) is a rare disease that can involve various organs, including the bone. Given the incidence of the disease in the global population, MS poses a challenge for physicians, and early therapeutic intervention in the initial stages could significantly impact the quality of life of affected patients. Objective: The aim of this scoping review was to provide an overview of secondary osteoporosis in systemic mastocytosis (SM), focusing on the heterogeneity of its manifestations, the benefits of early diagnosis, and appropriate pharmacological treatment. Design: A technical expert panel (TEP) consisting of 8 physicians with expertise in metabolic bone diseases conducted the review following the PRISMA-ScR model. A strength of this study is that it provides various therapeutic approaches for patients with bone involvement in SM, although the limited available literature on the topic constituted a limitation. The TEP sought evidence regarding the following diagnostic and therapeutic modalities in the management of SM: “bisphosphonate therapy”, “zoledronic acid therapy”, “denosumab therapy”, “IFN-alpha therapy”, and “IFN-alpha therapy in combination with pamidronate”. Results: Clinical data showed a correlation between densitometric outcomes, serum tryptase levels, and mast cell infiltration in the bone marrow, between increased bone mineral density and the presence of osteosclerosis in cases of advanced SM, between the severity of osteoporosis and hypertryptasemia, and also provided results on the long-term effects of bisphosphonate therapy, the therapeutic efficacy of zoledronic acid administration, the positive effect of denosumab on the reduction of serum tryptase levels (even if is proved in a limited numbers of cases) and the prevention of new fractures, and the effect of IFN-alpha in more severe cases of SM, either alone or in combination with pamidronate. Conclusions: Studies have demonstrated the effectiveness of various treatments depending on the form of mastocytosis, whether indolent systemic or advanced systemic, in the prognosis of the disease. However, this role should be further investigated in additional clinical studies, considering the limited data on the use of these interventions.

Ramadan fasting and exercise combination therapy: A novel approach for osteoporosis prevention in ovariectomized rats.

Osteoporosis is a chronic bone metabolic disease that affects millions of people worldwide, particularly the elderly and postmenopausal women. It is characterized by weakened bones, increasing the risk of fractures and leading to significant morbidity and mortality. The goal of the current study is to examine the reported osteo-preservative effects of exercise and/or fasting in the Ramadan fasting model (RFM) in ovariectomized (OVX) rats. The experimental intervention started 1month following the ovariectomy procedure and consisted of five 15-min exercise sessions per week at 18-25m/min and/or an approximately 13-h fast from sunrise to sunset (6:00 AM-19:00 PM). Serum bone metabolism biomarker levels were measured, and mineral concentrations in femoral ashed bones and digested serum were determined. Additionally, serum bone alkaline phosphatase (b-ALP), parathyroid hormone, osteocalcin, calcitonin, and vitamin D3 concentrations were measured using the competitive enzyme immunoassay technique. Calcium, magnesium, and phosphorus showed a notable decrease in mineral concentration among OVX rat femurs compared with the combination group (OVX + RFM + E) and control groups. In addition, homeostasis of serum concentrations of calcium, magnesium, and phosphorus was observed to increase in the OVX + RFM + E group rather than in the OVX group without intervention when compared with a control group. Furthermore, fasting and exercise, either alone or concurrently with ovariectomy, induced a non-significant elevation in osteocalcin, parathyroid hormone, and vitamin D3, whereas b-ALP and calcitonin increased significantly compared with those in control rats. The combination of the Ramadan fasting model and moderate intensity exercises among OVX rats manifested advantageous effects in bone biomarkers compared with OVX rats without intervention. This could be recommended as a lifestyle modification that is protective against osteoporosis, especially in the context of depleted estrogen hormone after menopause.

Identifying Child Abuse in Patients With Femur Fractures Through Pathway Compliance: A Pilot Study.

Background Child abuse is a significant cause of morbidity and mortality in children. A thorough history and physical exam is critical to identifying abuse. Standardized screening tools as well as clinical pathways can assist with identifying patients who may have an injury secondary to abuse. There are varied recommendations for the upper age in which to routinely evaluate pediatric patients for child abuse. Objectives The primary objective of this study was to describe the outcomes of the implementation of an evidence-based clinical pathway for suspected non-accidental trauma for all pediatric patients aged five years and under presenting with a femur fracture. This pathway includes orders for imaging, labs, and consults. In addition, the characteristics of this population and the findings were described. Methods A retrospective study of patients at a single institution who met the National Trauma Data Standard registry inclusion criteria and had a femur fracture was performed. Variables analyzed included age, demographics, mechanism and location of injury, admission status and service, injury severity, hospital characteristics, and discharge status. Patients with a metabolic bone disease were excluded. Results There were 200 patients who met the inclusion criteria. Thirty-two patients had a diagnosis of confirmed or suspected child abuse. While all 32 patients had a skeletal survey performed, only 23 (71.9%) had the complete workup per the clinical pathway, and 21 (65.6%) had a diagnosis of confirmed child abuse. Conclusion Clinical pathways are established to provide the standardization of clinical assessments and interventions; however, this process relies on a single individual to make a judgment determining whether or not to implement the pathway. Children presenting to an emergency department with confirmed or suspected child abuse are a vulnerable population. A child abuse diagnosis is a clinical judgment; however, clinical pathways aid in the diagnosis in hopes to stop any further abuse. For a pathway to be successful, each step needs to be addressed.

Identifying Gene Variants That Are Pathogenic In Osteoporosis Using An Omics Data And Bioinformatics Approach

Introduction. The biological cause of osteoporosis, a metabolic bone disease, is osteoclastic bone resorption that is not offset by osteoblastic bone synthesis. Fractures become more likely as a result of the bones being brittle and weak. Common genetic variants that indicate hereditary susceptibility factors to osteoporosis in the general population, as well as mutations affecting specific genes that cause uncommon monogenic causes of osteoporosis, are the two main types of osteoporosis. Bone defects can now be caused by numerous additional genes. In this study, we aimed to identify variants of this pathogen across continents using genome-based and bioinformatics methodologies. Methods. We integrated osteoporosis-associated variants into this study using various bioinformatics-based techniques by using GWAS data from the National Human Genome Research Institute (NHGRI). Results. We found that the variant rs3742909 is likely to cause osteoporosis. SMOC1 gene expression in whole blood tissue also appears to be affected by this variant. We found that this genomic variant requires additional research to validate functional and clinical studies in patients with osteoporosis. Conclusions. We suggest that better understanding of disease susceptibility, including osteoporosis, can be achieved through the merging of genome-based databases and bioinformatics. Our goal is to validate the findings of this study both in vitro and in vivo during the preclinical stage.

Important practical aspects in the management of patients with shot bowel syndrome and intestinal failure

Short bowel syndrome is a gastrointestinal disorder resulting from massive resection of the small intestine. The most common causes of resection are acute mesenteric ischemia, Crohn’s disease, abdominal trauma, adhesive intestinal obstruction, intestinal malignancies, and radiation enteritis. Short bowel syndrome with intestinal failure is characterized by severe malabsorption-m aldigestion accompanied by abdominal pain, diarrhea, dehydration, and progression of protein-energy malnutrition. Many patients with SBS develop long-term clinical complications over time due to altered bowel anatomy and physiology or various therapeutic interventions such as parenteral nutrition and central venous catheterization. This review focuses on the most important aspects of diagnosis, treatment, and prevention of several complications that can occur in this patient population, including macronutrient and micronutrient imbalances, diarrhea, fluid and electrolyte imbalances, metabolic bone disease, biliary disorders, bacterial overgrowth in the small intestine, and complications related to venous access. The main therapeutic strategies for SBS with intestinal failure are: special diet, enteral nutritional support with semi-elemental mixtures, parenteral nutrition, oral rehydration, antimicrobal and antidiarrheal drugs, enzymes. Administration of glucagon-like peptide 2 analog, teduglutide, is clinically effective in reducing dependence on parenteral nutrition and improving quality of life. Management of patients with SBS with intestinal failure is a complex long-term process which requires dynamic clinical and laboratory monitoring.

The Role of Mitochondrial Permeability Transition in Bone Metabolism, Bone Healing, and Bone Diseases.

Bone is a dynamic organ with an active metabolism and high sensitivity to mitochondrial dysfunction. The mitochondrial permeability transition pore (mPTP) is a low-selectivity channel situated in the inner mitochondrial membrane (IMM), permitting the exchange of molecules of up to 1.5 kDa in and out of the IMM. Recent studies have highlighted the critical role of the mPTP in bone tissue, but there is currently a lack of reviews concerning this topic. This review discusses the structure and function of the mPTP and its impact on bone-related cells and bone-related pathological states. The mPTP activity is reduced during the osteogenic differentiation of mesenchymal stem cells (MSCs), while its desensitisation may underlie the mechanism of enhanced resistance to apoptosis in neoplastic osteoblastic cells. mPTP over-opening triggers mitochondrial swelling, regulated cell death, and inflammatory response. In particular, mPTP over-opening is involved in dexamethasone-induced osteoblast dysfunction and bisphosphonate-induced osteoclast apoptosis. In vivo, the mPTP plays a significant role in maintaining bone homeostasis, with many bone disorders linked to its excessive opening. Genetic deletion or pharmacological inhibition of the over-opening of mPTP has shown potential in enhancing bone injury recovery and alleviating bone diseases. Here, we review the findings on the relationship of the mPTP and bone at both the cellular and disease levels, highlighting novel avenues for pharmacological approaches targeting mitochondrial function to promote bone healing and manage bone-related disorders.

Understanding the relationship between inflammation, apoptosis, and diabetes osteoporosis: A bioinformatics approach and experimental verification.

Diabetes osteoporosis (DOP) is a chronic metabolic bone disease. This study aimed to identify potential biomarkers of DOP and explore their underlying mechanisms through bioinformatics methods and experimental verification. Bioinformatics methods were used to identify differentially expressed genes (DEGs) for DOP based on GEO data and the GeneCards database. GO and KEGG enrichment analyses were used to search the key pathways. The STRING website was used to construct a protein-protein interaction (PPI) network and identify key genes. Then, 50 mg/mL glucose was used to interveneosteoblasts (OBs).CCK-8 and Alizarin Red staining were used to investigate the proliferation and differentiation changes in OBs. Flowcytometry was used to investigate apoptosis. The membrane protein chip, WB, and RT-PCR were used to verify the expression of key targets or pathways about DOP. Forty-two common genes were screened between DOP-related targets and DEGs. GO and KEGG enrichment analysis showed that DOP was mainly associated with cytokine-cytokine receptor interactions, and apoptosis. PPI network analysis showed that TNF, IL1A, IL6, IL1B, IL2RA, Fas ligand (FASLG), and Fas cell surface death receptor (FAS) were key up-regulated genes in the occurrence of DOP. The experiment results show that 50 mg/mL glucose significantly inhibited OBs proliferation but presented an increase in apoptosis. Membrane protein chip, WB, and RT-PCR-verified a significantly active in the expression of TNF/FASLG/FAS pathway. High glucose activated the TNF-α/FAS/FASLG pathway and induced the inflammatory microenvironment and apoptosis, then impaired osteogenic differentiation of OBs. These may be an important mechanism for the occurrence and development of DOP.

Challenges of Hip and Knee Arthroplasty in Patients With Osteopetrosis.

Osteopetrosis is a rare metabolic bone disease, characterized by dysfunction of osteoclasts, resulting in increased bone density and brittleness leading to pathological fractures and bone deformities. Hip and knee osteoarthritis (OA) are common long-term complications in patients with osteopetrosis. Joint arthroplasty surgery remains an effective and recommended treatment for these patients with an end-stage OA because it provides favorable outcomes. However, in osteopetrosis, joint arthroplasty surgery carries an increased risk of complications, and specific preoperative and perioperative considerations are required to deal with the technical challenges related to the disease. The aim of this article was to review some of the key aspects of osteopetrosis, provide technical recommendations, and answer clinically relevant questions related to hip and knee arthroplasty surgery.