Bone Metabolism Research Articles

Comorbidity problems in patients with osteoporosis

BACKGROUND: Osteoporosis is a metabolic skeletal disease characterized by decreased bone mass, impaired microarchitecture of bone tissue and, as a consequence, fractures with minimal trauma. The social significance of osteoporosis is determined by its consequences — fractures of the vertebral bodies and bones of the peripheral skeleton, leading to high medical costs and causing a high level of disability, including disability and mortality. Osteoporosis is most often combined with cardiovascular diseases caused by atherosclerosis, which are widespread and are the leading cause of disability and mortality. A small number of studies have been devoted to the study of the features of clinical manifestations of cardiovascular diseases in the combination of coronary heart disease and osteoporosis. AIM: To identify the frequency and severity of comorbid diseases and their risk factors in postmenopausal osteoporosis. MATERIALS AND METHODS: A retrospective and prospective cohort study was conducted from 2013 to 2023. 8250 women with postmenopausal osteoporosis were examined and the data from the medical records of these patients who applied to the Osteoporosis Center of the North-Western State Medical University named after I.I. Mechnikov of the Ministry of Health of the Russian Federation from 2013 to 2020 were analyzed. At the prospective stage, two comparison groups of 100 patients with and without postmenopausal osteoporosis were formed from 500 patients with comorbid diseases (coronary heart disease, hypertension, type 2 diabetes, stroke, transient ischemic attack). Bone mineral density was assessed based on the Hologic Discoveri Wi dual-energy X-ray absorptiometry at 2 points in the lumbar spine (L1–L4) and the femoral neck. Along with traditional laboratory examination methods, bone metabolism markers (total calcium, phosphorus, vitamin D, urine analysis for deoxypyridinoline, C-terminal telopeptide of type 1 collagen, osteocalcin, alkaline phosphatase, parathyroid hormone) were assessed dynamically. In all the patients, along with a general clinical examination, an assessment of risk factors for cardiovascular disease and osteoporosis was performed. RESULTS: Body mass index was higher in the group of patients with osteoporosis — 28.4 (26.9–32.4) kg/m2 (p 0.001), versus 27.64 (25.8–30.0) kg/m2 (p 0.05). Bone mineral density in the group of patients with osteoporosis was statistically lower than in the group without osteoporosis. In the group of patients with osteoporosis, the risk of fractures was high and amounted to 37 (95% confidence interval 15.0–38.50) %, p 0.001), versus in the control group 9.55 (95% confidence interval 7.67–15.0) % (p 0.001) according to the FRAX questionnaire for the Russian Federation. In the group of patients with osteoporosis, the Charlson index values were 5.1 (95% confidence interval 4.7–5.6) points. As a result of the correlation analysis, a reliable positive relationship was revealed between low bone mineral density L1–L4 and hip with bone metabolism: alkaline phosphatase, C-terminal telopeptide of type 1 collagen, vitamin D, osteocalcin, urinary deoxypyridinoline. We found a negative relationship between bone mineral density and the Charlson index, absolute ten-year risk of hip fracture and the duration of early menopause, and the level of hypertension. To assess the dependence of QRISK3-2018 on osteoporosis risk factors in the group of patients with osteoporosis, multiple linear regression was performed. This model was characterized by a statistically significant correlation between the factors and the dependent variable of high tightness. The coefficient of determination was 0.608, indicating a 60.8% contribution of the factors taken into account in the model to the variance of QRISK3-2018. CONCLUSIONS: In women with postmenopausal osteoporosis, comorbid pathology is more common, aggravating the course of the disease. Knowledge of the prevalence of concomitant pathology and joint risk factors will make it possible to simultaneously form groups at increased risk of development, which will ensure prevention of both diseases with the same non-medical means and drugs.

Seasonal differences of 25-hydroxyvitamin D concentrations in children and adolescents from Mexico City and Metropolitan Area

Introduction: Vitamin D deficiency is associated with bone metabolism and immune disorders. Radiation's seasonal variation affects vitamin D status more at the poles. In Mexico, near the equator, there have been reports of 10-20% vitamin D deficiency in children. There is no consensus on the definition of vitamin D deficiency, different organizations consider that a vitamin D level should be above 20 to 30 ng/ml. This study aimed to analyze vitamin D serum concentrations in children and adolescents from Mexico City and the Metropolitan Area (MA) during different seasons. Methods: Cross-sectional study in children and adolescents aged 5-20 years from Mexico City and Metropolitan Area, from autumn 2016 to winter 2017. Variables of interest such as anthropometric measurements, food consumption, and physical activity were analyzed. Results: A total of 816 children and adolescents were included. A high frequency of vitamin D deficiency was detected in 40.7% of the sample. The lowest vitamin D status occurred in winter 2016 and winter 2017. Conclusion: We found a higher frequency of vitamin D deficiency during winter in children and adolescents in Mexico City and MA. This risk persisted after adjusting for age, sex, BMI Z-score, milk consumption, physical activity, and screen time.

Fracture severity dependence of bone and muscle performance in patients following single or multiple vertebral fractures

BackgroundFew studies focus on the clinical, laboratory, radiological, and biological characteristics of bone and muscle of multiple vertebral fractures, which are associated with a more poor prognosis compared with single fracture.PurposeTo compare the BMD, bone turnover, muscularity, fatty infiltration of muscle, and prevalence of co-morbidities in patients with single and multiple vertebral fractures.MethodsWe recruited 100 patients with single fracture (age 66.96 ± 8.24 years) and 100 with multiple fractures (age 69.90 ± 7.80 years); performed dual-energy X-ray absorptiometry of the femoral neck, hip, and lumbar vertebrae; and measured biochemical markers of bone turnover, muscularity, and fatty infiltration.ResultsPatients with multiple vertebral fractures had lower hip BMD (p=0.010) than those with single fractures, but there was no difference in femoral neck and lumbar vertebral BMD nor in muscularity. However, fatty infiltration, an indicator of muscle quality, was significantly higher in participants with multiple fractures (p=0.006). Diabetes was significantly more common in patients with multiple fractures (p=0.042). There were no significant differences in markers of bone turnover, and Seperman analyses showed no correlations of CTX-1 or tPINP with the BMD of the hip, femoral neck, or lumbar spine. However, high CTX-1 was associated with high tPINP (r=0.4805; p<0.0001), and marked fatty infiltration was associated with low hip, lumbar vertebral, and femoral neck BMD. Cox regression analyses showed that age (OR 1.057; 95% CI 1.016–1.101; p=0.006) and low hip BMD (OR 0.016; 95% CI, 0.000–0.549; p=0.022) were associated with a higher risk of multiple fractures.ConclusionPatients with multiple fractures tend to have lower hip BMD, a history of type 2 diabetes, and more substantial fatty infiltration of muscle than in those with single fractures. Age and hip BMD rather than lumbar vertebrae BMD were found to be independent risk factors for multiple vertebral compression fractures, implying that hip BMD may be a more sensitive predictor for multiple vertebral fractures. More improvements in hip BMD and focus on older persons may be useful means of preventing multiple fractures.

Hormonal Contraceptive Use and Physical Performance, Body Composition, and Musculoskeletal Injuries during Military Training.

Purpose: To investigate associations between hormonal contraceptive use and physical performance, body composition, and musculoskeletal injuries in basic military training.Methods: Female British Army recruits (n = 450) were grouped as non-users (n = 182), combined oral contraceptive users (COCP; n = 184), or progestin-only users (POC; n = 144). Physical performance (2.4 km run, lift strength, leg power), body composition, iron and vitamin D status, and bone metabolism were measured at the start (week 1) and end (week 13) of training. Lower body musculoskeletal injuries were recorded from medical records.Results: Training decreased 2.4 km run time (-3.7%) and fat mass (-9.6%), and increased lift strength (4.5%), leg power (1.5%), lean mass (5.4%), and whole-body (0.9%), arms (1.8%), and legs (1.4%) aBMD (p ≤ 0.015); the training response was not different between groups (p ≥ 0.173). Lift strength was lower in COCP users than non-users (p = 0.044). Whole-body, trunk, and legs aBMD were lower in POC users than non-users and/or COCP users (p ≤ 0.041). There were no associations between hormonal contraceptive use and musculoskeletal or bone stress injury (p ≥ 0.429). Training did not change ferritin (p = 0.968), but decreased haemoglobin and total 25(OH)D, and increased PTH, βCTX, and PINP (p ≤ 0.005); the training response was not different between groups (p ≥ 0.368). Total 25(OH)D was higher, and βCTX and PINP were lower, in COCP users than non-users and POC users; PTH was lower in COCP users than non-users, and; βCTX and PINP were higher in POC users than non-users (p ≤ 0.017).Conclusions: Hormonal contraceptive use was not associated with performance or injury outcomes in military training.

Yigu decoction regulates plasma miRNA in postmenopausal osteoporosis patients: a randomized controlled trial

BackgroundPostmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD.MethodsIn this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism.ResultsCompared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins.ConclusionThis study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.

The effect of cold atmospheric plasma on viability of osteoblasts and expression of RANKL and OPG genes in medium with bisphosphonates.

Medication-related osteonecrosis of the jaw is a rare but severe complication with challenging treatment protocols. Cold atmospheric plasma (CAP) has shown promising effects in wound healing, cell proliferation and viability. This study investigated the effect of CAP on osteoblasts in a culture medium containing bisphosphonates. Pilot study was designed to determine the optimal setting of CAP. MG-63 cells were exposed to zoledronic acid at a concentration of 10 micromolar for 72h. Study groups with the best MTT assay results, were chosen for assessing OPG and RANKL genes by RT-PCR. Cell viability was significantly higher in groups 9kV.1mm.90s, 10kV.1mm.60s, and 12kV.1mm.60s (P < 0.05). Expression of RANKL in these groups was significantly lower than the positive control group (medium culture without zoledronic and plasma treatment) and higher than the BP group (culture with zoledronic without plasma treatment), except for the 12kV.1mm.60s group, which did not differ significantly from the positive control group (P > 0.05). OPG decreased in all test groups compared to BP (p < 0.05), except for the 12kV.1mm.60s group, which did not significantly differ from BP (P > 0.05). RANKL/OPG ratio in groups 9kV.1mm.90s and 12kV.1mm.60s significantly increased compared to BP (P < 0.05).CAP treatment may enhance the viability of osteoblasts exposed to bisphosphonates, increase their activity levels, enhance osteoclast activity, and improve bone turnover rates.

The association between metabolite profiles and impaired bone microstructure in adult growth hormone deficient rats.

Adult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency. Thirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels. Adult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD. Adult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.

Gastrointestinal health and serum proteins are associated with BMD in postmenopausal women: a cross-sectional study.

With increasing age, the social and economic burdens of postmenopausal osteoporosis are steadily increasing. This study aimed to investigate the factors that influence the development of postmenopausal osteoporosis. Postmenopausal women at the Affiliated Hospital of Jiangnan University from January 2023 to December 2023 were recruited for BMD examination. The patients were divided into a normal group, an osteopenia group and an osteoporosis group according to their T value. Questionnaires, including the Gastrointestinal Symptom Rating Scale and Short Form 12, were administered through face-to-face interviews. Bone turnover markers and serum protein levels of Fasting venous blood were detected. A total of 222 postmenopausal women met the inclusion criteria were recruited. Univariate analysis revealed statistically significant differences in age, education, BMI, supplementation with soy products, supplementation with dairy products, supplementation with other nutritional supplements, exercise frequency, gastrointestinal symptom score, quality of life, 25(OH)D, total protein, albumin and prealbumin among the three groups (P < 0.05). Pearson correlation analysis revealed that gastrointestinal symptoms (r = -0.518, P < 0.01) was negatively correlated with BMD in postmenopausal women, while PCS (r = 0.194, P = 0.004), MCS (r = 0.305, P < 0.01), 25(OH)D (r = 0.531, P < 0.01), total protein (r = 0.324, P < 0.01), albumin (r = 0.341, P < 0.01) and prealbumin (r = 0.259, P < 0.01) were positively correlated with BMD. Logistic regression analysis revealed that both the gastrointestinal symptom score and serum 25(OH)D level were found to have a significant association with BMD (both P < 0.01). This association remained significant even after adjusting for age, BMI, education level, dietary habits, and exercise frequency. Gastrointestinal symptoms and serum 25(OH)D elevel are associated with increased risk of osteoporosis in postmenopausal women and may be useful in predicting osteoporosis in postmenopausal women.

Magnesium Membrane Shield Technique for Alveolar Ridge Preservation: Step-by-Step Representative Case Report of Buccal Bone Wall Dehiscence with Clinical and Histological Evaluations

Background/Objectives: Despite the increased use of new resorbable magnesium membranes, there are no reported cases or studies on the use of resorbable magnesium membranes in combination with bone grafts for alveolar ridge preservation (ARP) in cases with severe buccal bone wall dehiscence. This case report aimed to evaluate the effectiveness of the magnesium membrane shield technique in conjunction with bone grafting for ARP, assessing both clinical outcomes and histological bone regeneration. Methods: A 44-year-old female patient presented with a vertical fracture on tooth 24 (FDI Notation System) accompanied with complete destruction of the buccal bone wall. The treatment plan included tooth extraction, ARP using a combination of anorganic bovine bone and autologous bone grafting, and the application of a magnesium membrane as a shield to the pre-existing buccal wall. Six months post-procedure, a bone biopsy was taken from the implant site using a trephine bur. Results: Clinical and radiological evaluations six months after the procedure demonstrated sufficient bone volume for implant placement. Additionally, in the next three months, soft tissue conditioning with a provisional crown resulted in an aesthetically and functionally satisfactory outcome. Histological analysis of the bone biopsy revealed well-formed new bone in direct contact with residual biomaterial, with no signs of inflammation. Osteocytes were clearly visible within the newly formed bone matrix, indicating successful bone maturation. Active osteoblasts were observed along the bone-biomaterial interface, suggesting ongoing bone remodeling and integration. Additionally, histomorphometric evaluation revealed 47% newly formed bone, 32% soft tissue, and 19% residual biomaterial. Conclusions: This case demonstrates the potential of the magnesium shield technique as an ARP technique in cases with severe buccal wall dehiscence. The technique yielded satisfactory clinical outcomes and promoted successful bone regeneration, as confirmed by histological analysis.

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.

Acupuncture-induced gene co-expression networks in postmenopausal women with osteoarthritis and osteoporosis: In-silico analysis.

Objective: Bone is a tissue that is constantly remodeled to adjust the microarchitecture and maintain the mechanical needs of bone through the balance of bone resorption and formation processes. Alterations in these processes can lead to the development of different diseases, such as osteoarthritis and osteoporosis. In recent years, it has been shown that acupuncture is an effective treatment for pain, physical dysfunctions, and the immune system, so the stimulation of acupuncture points could affect genes associated with inflammatory processes and, therefore, osteoarthritis and osteoporosis. To analyze changes in gene expression post-acupuncture in data from a group of individuals with osteoarthritis that also manifests in osteoporosis. Method: Through using microarray technology and bioinformatics analysis, potential genes associated with osteoarthritis after acupuncture treatment are identified and compared with genes implicated in osteoporosis. The genes identified in each disease were evaluated through a KEGG signaling pathway analysis, where the results allowed the generation of an in-silico model that shows interaction networks between signaling pathways and genes involved in both diseases. Results: In this interaction, 37 differentially expressed genes were identified in patients with osteoarthritis before and after acupuncture treatment, and 665 differentially expressed genes was involved in osteoporosis. In the osteoarthritis group, 15 signaling pathways involved in this disease were obtained, and for osteoporosis, 13 signaling pathways associated with immunological processes that participate in bone metabolism were obtained osteoarthritis and osteoporosis are two age-associated diseases that are characterized by alterations in the bone remodeling mechanism induced by changes in gene expression profiles. Conclusions: Treatment with acupuncture can modify various cytokines involved in diseases related to the immune system so that it can have beneficial effects on osteoarthritis and osteoporosis. In addition, bioinformatics analysis allows us to know those signaling pathways through which they could have acupuncture effects. Graphical abstract: http://links.lww.com/AHM/A137.

Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia.

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically-determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and four BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an AUC of 0.962 with a cut-off of 32μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32U/L (i.e., the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment.

Sonification of Deproteinized Bovine Bone Functionalized with Genistein Enhances Bone Repair in Peri-Implant Bone Defects in Ovariectomized Rats

Estrogen deficiency is one of several contributing factors to catabolic changes in bone surrounding dental implants, impairing bone repair in defects requiring bone regeneration. Functionalizing bone substitutes is an alternative approach among various strategies to address this challenge. In this study, the aim was to evaluate the effect of functionalizing deproteinized bovine bone (Bio-Oss®, BO) with genistein via sonication on peri-implant bone defects in ovariectomized rats. The animals were randomly distributed according to the treatment into the following four groups (n = 10): BO sonicated with genistein (BOS + GEN), BO sonicated alone (BOS), untreated BO (BO), and blood clot only (CLOT). After twenty-eight days, implant removal torque was determined, and the peri-implant bone parameters were calculated based on computed microtomography. Additionally, the gene expression of bone turnover markers was evaluated. As a main result, the functionalization with genistein increased implant removal torque and the peri-implant bone volume in the BOS + GEN group compared to both BOS and BO groups (both p &lt; 0.05). These findings suggest that the sonification of deproteinized bovine bone functionalized with genistein improves bone repair in peri-implant bone defects in ovariectomized rats.

Luteolin inhibits orthodontic tooth movement and relapse

Luteolin is a natural flavonoid compound that widely exists in human food. Studies have demonstrated luteolin has powerful anti-inflammatory properties and can affect bone remodeling in an inflammatory environment. This study aimed to investigate the effect of luteolin on orthodontic tooth movement (OTM) and relapse after OTM. Male Sprague Dawley rats were randomly divided into 3 groups (n= 8): OTM, 50 mg/kg/d luteolin, and 100 mg/kg/d luteolin. Then, 50 g of orthodontic force was applied to all animals. A saline solution or corresponding concentration of luteolin was given orally. For the OTM experiment, after 14 days of force application, rats were killed, the maxilla was dissected, and then microcomputed tomography, histologic staining, and western blotting were performed. For the relapse experiment, the spring was removed, and a silicone impression was made to record the relapse status. Compared with the OTM alone group, systemic administration of luteolin inhibited OTM and tooth relapse (P<0.05). Increased bone volume, reduced osteoclast activity, and a decrease in osteoclastogenesis-related protein expression were observed in luteolin-treated groups. These effects may be attributed to the inhibition of the nuclear factor-kappa B pathway. Luteolin can significantly inhibit OTM and relapse after OTM. Thus, luteolin is a prospective candidate for enhancing tooth anchorage and preventing relapse in orthodontic treatment.

Unlocking the Epigenetic Symphony: Histone Acetylation Orchestration in Bone Remodeling and Diseases.

Histone acetylation orchestrates a complex symphony of gene expression that controls cellular fate and activities, including the intricate processes of bone remodeling. Despite its proven significance, a systematic illustration of this process has been lacking due to its complexity, impeding clinical application. In this review, we delve into the central regulators of histone acetylation, unveiling their multifaceted roles in modulating bone physiology. We explore both contradictory and overlapping roles among these regulators and assess their potential as therapeutic targets for various bone disorders. Furthermore, we highlight current applications and discuss looming questions for a more effective use of epigenetic therapy in bone diseases, aiming to address gaps in knowledge and clinical practice. By providing a panoramic view of histone acetylation's impact on bone health and disease, this review unveils promising avenues for therapeutic intervention and enhances our understanding of skeletal physiology, crucial for improving therapeutical outcomes and quality of patients' life.

Clinical, Laboratory, and Molecular Characteristics of Inherited Vitamin K-Dependent Coagulation Factors Deficiency.

Vitamin K-dependent coagulation factors deficiency (VKCFD) is a rare autosomal recessive genetic disease characterized by impaired levels of multiple coagulation factors (II, VII, IX, and X) and natural anticoagulants (proteins C and S). VKCFD is part of familial multiple coagulation factor deficiencies, reporting overall 50 affected families thus far. Disease manifestations are quite heterogeneous, bleeding symptoms may vary, and even, although generally mild, some patients may succumb to fatal outcomes. VKCFD diagnosis may be delayed because the disease phenotype simulates the most frequently acquired deficiencies of vitamin K. First-line coagulation assays, prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT), are both prolonged; mixing test typically normalizes the clotting times; and vitamin K-dependent coagulation factors will be variably decreased. Molecularly, VKCFD is associated with mutations in γ-glutamyl-carboxylase (GGCX) or vitamin K epoxide reductase complex subunit 1 (VKORC1) genes. Vitamin K is involved not only in the biosynthesis of coagulation proteins but also in bone metabolism and cell proliferation. Therapeutic options are based on vitamin K supplementation, coagulation factors (prothrombin complex), and fresh frozen plasma, in case of severe bleeding episodes. Two case studies here illustrate the diagnostic challenges of VKCFD: case 1 depicts a woman with a history of bleeding episodes, diagnosed, only in her third decade of life with inherited homozygous GGCX gene mutation. Case 2 shows a man with an acquired vitamin K deficiency caused by Crohn's disease. Better understanding of GGCX and VKORC1 mutations aids in prognosis and treatment planning, with emerging insights suggesting potential limitations in the effectiveness of vitamin K supplementation in certain mutations.

Predictive value of bone metabolism markers in the progression of diabetic kidney disease: a cross-sectional study

ObjectiveThis study aimed to investigate the relationship between bone metabolism markers, including serum klotho, fibroblast growth factor 23 (FGF23), 25(OH)D3, iPTH, calcium (Ca), and PHOS and the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Additionally, the predictive value of these markers for DKD progression was evaluated.MethodsThis study involved 126 patients with T2DM between May 2021 and March 2023. DKD staging was assessed based on urinary protein excretion rates and estimated glomerular filtration rate (eGFR). The study evaluated serum concentrations of klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS across various stages and examined their relationships with clinical parameters. Receiver operating characteristic (ROC) curve analysis was utilized to determine the predictive accuracy of these bone metabolism markers for DKD. Multivariate linear and logistic regression analyses identified risk factors linked to DKD severity.ResultsAmong the 126 participants, 30 had non-DKD with normal proteinuria, while 96 had DKD, categorized as 31 with stage III DKD (microproteinuria), 34 with stage IV DKD, and 31 with stage V DKD (massive proteinuria). With advancing DKD from stage III to V, levels of klotho, 25(OH)D3, and Ca decreased significantly, whereas FGF23, iPTH and PHOS levels increased markedly. Klotho is significantly positively correlated with eGFR (r = 0.285, P = 0.001.) and negative correlations with serum creatinine (Scr) and UACR (r = -0.255, P = 0.004; r = -0.260, P = 0.011). FGF23 was positively related to systolic blood pressure (SBP) (r = 0.224, P = 0.012), but negatively with eGFR (r = -0.294, P = 0.001). Additionally, 25(OH)D3 exhibited significant negative correlations with several adverse clinical biomarkers, and both iPTH, Ca and PHOS were strongly associated with DKD progression (P&amp;lt;0.05). ROC analysis showed high predictive accuracy for DKD using these bone metabolism markers, with a combined area under the curve (AUC) of 0.846. Multivariate logistic regression analysis reinforced the significance of these markers in DKD progression.ConclusionBone metabolism markers, such as klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS are intricately linked to DKD progression and may function as valuable predictive biomarkers.

Bone Mineral Density, C-Terminal Telopeptide of Type I Collagen, and Osteocalcin as Monitoring Parameters of Bone Remodeling in CML Patients Undergoing Imatinib Therapy: A Basic Science and Clinical Review

Background: Chronic myeloid leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a tyrosine kinase inhibitor (TKI), can be effectively used as therapy for CML. However, Imatinib can affect bone turnover thus having clinical implications on the bones of CML patients undergoing long-term Imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving Imatinib still need further study. A combination of imaging techniques such as bone mineral density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving Imatinib. Objectives: This article explains the rationale for using BMD, CTX-1, and osteocalcin as monitoring parameters of bone remodeling in CML patients receiving Imatinib. Results: First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of Imatinib on BMD, CTX-1, and osteocalcin will be explained. Conclusion: The assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and osteocalcin.

Romosozumab for the treatment of osteoporosis - a systematic review.

Romosozumab, a new treatment of osteoporosis, is a monoclonal antibody that targets sclerostin and thereby exhibits a dual mechanism of action by stimulating bone formation and inhibiting bone resorption. This systematic review aims to assess the clinical efficacy and safety of romosozumab for treatment of primary and secondary osteoporosis. A comprehensive literature search was conducted in October 2023 across multiple databases including Embase, PubMed and Cochrane Library. Randomized controlled trials (RCTs) and observational studies evaluating the impact of romosozumab on BMD, bone turnover markers (BTM), fracture outcomes, and its safety profile were included. Data extraction and quality assessment were performed independently by two reviewers in accordance with PRISMA guidelines. A total of 36 articles met the inclusion criteria. Romosozumab significantly increased BMD at the lumbar spine, total hip, and femoral neck compared to placebo and active comparators in patients with primary osteoporosis. Sequential therapy with romosozumab followed by antiresorptives maintained or further increased BMD and reduced fracture risk. Romosozumab was generally well tolerated, however, an imbalance in cardiovascular adverse event was observed in one large clinical trial. Observational studies supported these findings. Specific subgroups of patients with secondary osteoporosis were assessed, demonstrating overall positive outcomes with romosozumab treatment. Romosozumab effectively increases BMD and reduces fracture risk, particularly when used as initial therapy in high fracture-risk patients. Sequential therapy with subsequent antiresorptive treatment optimizes long-term benefits. While generally well-tolerated, its cardiovascular safety profile requires further long-term studies to ensure its safety in clinical practice. Additional studies are needed to confirm efficacy and safety in patients with secondary osteoporosis.