Osteoporosis Research Articles

Alendronate preserves bone mineral density in adults with sickle cell disease and osteoporosis.

To describe the effects of alendronate in adults with sickle cell disease (SCD) and osteoporosis. We reviewed retrospective clinical data from adults with SCD and osteoporosis treated with alendronate at a single center in Brazil (2009-2019). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and total hip. We analyzed BMD changes by alendronate treatment duration (months), stratified by sex, skeletal site, and SCD genotype. Sixty-four SCD adults with osteoporosis (69% females, 73% HbSS, mean age ± standard deviation 42.4 ± 10.9years) received alendronate for a median (interquartile range) of 48 (29, 73) months. Compared with males, females had significantly lower baseline BMD (g/cm2) at the femoral neck (0.72 vs 0.85, p = < 0.001) and total hip (0.79 vs 0.88, p = 0.009). The between-sex differences in BMD changes were insignificant. Mean lumbar spine BMD significantly changed by 0.0357g/cm2 (p = 0.028) in those on alendronate for > 5years. Four adults (6.3%) reported mild therapy-related side effects. An atypical femoral diaphysis fracture, attributed to alendronate, was incidentally noted in a 37-year-old man on treatment for 4years. In this retrospective cohort of adults with SCD and osteoporosis on alendronate for a median of 48months, we found no significant interactions between sex and changes in lumbar spine, femoral neck, or total hip BMD with alendronate. Lumbar spine BMD was stable in those on alendronate for < 5years. Side effects of alendronate were mild, though one patient developed an atypical femoral fracture.

Divergent associations of inflammatory markers with bone turnover markers in elderly patients with osteoporotic fractures

The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient’s complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (β = -1.1788, 95% CI: -1.7230 to -0.6345, P-value < 0.0001) and β-C-terminal telopeptide of type I collagen (β-CTX) (β = -0.0104, 95% CI: -0.0145 to -0.0062, P-value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (β = -17.4523, 95% CI: -27.7335 to -7.1710, P-value = 0.0009) and β-CTX (β = -0.1327, 95% CI: -0.2211 to -0.0443, P-value = 0.0034). However, PLR indicated a positive correlation with P1NP (β = 0.0326, 95% CI: 0.0007 to 0.0645, P-value = 0.0458) and β-CTX (β = 0.0003, 95% CI: 0.0001 to 0.0006, P-value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, β-CTX. In addition, the stratified analysis validated the result’s stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with β-CTX, whereas PLR demonstrates a positive correlation with β-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism.

A novel framework for elucidating the effect of mechanical loading on the geometry of ovariectomized mouse tibiae using principal component analysis.

Murine models are used to test the effect of anti-osteoporosis treatments as they replicate some of the bone phenotypes observed in osteoporotic (OP) patients. The effect of disease and treatment is typically described as changes in bone geometry and microstructure over time. Conventional assessment of geometric changes relies on morphometric scalar parameters. However, being correlated with each other, these parameters do not describe separate fractions of variations and offer only a moderate insight into temporal changes. The current study proposes a novel image-based framework that employs deformable image registration on in vivo longitudinal images of bones and Principal Component Analysis (PCA) for improved quantification of geometric effects of OP treatments. This PCA-based model and a novel post-processing of score changes provide orthogonal modes of shape variations temporally induced by a course of treatment (specifically in vivo mechanical loading). Errors associated with the proposed framework are rigorously quantified and it is shown that the accuracy of deformable image registration in capturing the bone shapes (∼1 voxel = 10.4μm) is of the same order of magnitude as the relevant state-of-the-art evaluation studies. Applying the framework to longitudinal image data from the midshaft section of ovariectomized mouse tibia, two mutually orthogonal mode shapes are reliably identified to be an effect of treatment. The mode shapes captured changes of the tibia geometry due to the treatment at the anterior crest (maximum of 0.103mm) and across the tibia midshaft section and the posterior (0.030mm) and medial (0.024mm) aspects. These changes agree with those reported previously but are now described in a compact fashion, as a vector field of displacements on the bone surface. The proposed framework enables a more detailed investigation of the effect of disease and treatment on bones in preclinical studies and boosts the precision of such assessments.

Sinonasal Phosphaturic Mesenchymal Tumors Without Any Nasal Symptoms: A Case Report and Literature Review.

We present a case of phosphaturic mesenchymal tumor (PMT) in the left ethmoid without any nasal symptoms in a 63-year-old woman. Initially diagnosed with postmenopausal osteoporosis, 2-year history of hypophosphatemia and a significantly higher uptake of Fluorine-18 (18F)-AlF-NOTA-octreotide (18F-OC) in the left ethmoid sinus, provided crucial information for accurate diagnosis. We presented a case with chart review and conducted review of the literature. The patient endured 1-year history of weakness and bone pain but without any nasal symptoms before a tissue diagnosis was eventually reached. It is a challenging diagnosis to make-patients present with non-specific clinical symptoms and the culprit neoplasm is often tiny in size and difficult to detect. It emphasizes the importance of thorough patient history-taking and the whole-body functional imaging. Sinonasal PMTs are rare, and because of this most otolaryngologists are unfamiliar with its clinical presentation. This case highlights the importance of early diagnosis to enable prompt intervention and reduce the burden of associated symptoms.

The biology of water homeostasis.

Water homeostasis is controlled by a brain-kidney axis that consists of central osmoreceptors, synthesis and secretion of arginine vasopressin (AVP) and AVP-responsive aquaporin-2 (AQP2) water channels in kidney collecting duct principal cells that facilitate water reabsorption. In addition to AVP, thirst represents a second line of defense to maintain water balance. Water balance disorders arise because of deficiency, resistance or inappropriate secretion of AVP or disturbances in thirst sensation (hypodipsia, polydipsia). People with water balance disorders are prone to develop hyponatremia or hypernatremia, which expose cells to osmotic stress and activate cell volume regulation mechanisms. This review covers several recent insights that have expanded our understanding of central osmoregulation, AQP2 regulation and cell volume regulation. This includes the role of with-no-lysine kinase 1 (WNK1) as a putative central osmolality sensor and, more generally, as an intracellular crowding sensor that coordinates the cell volume rescue response by activating sodium and potassium cotransporters. Furthermore, several new regulators of AQP2 have been identified, including for AVP-dependent AQP2 regulation (yes-associated protein, nuclear factor of activated T-cells, microRNAs) and AVP-independent AQP2 regulation (epidermal growth factor receptor, fluconazole, prostaglandin E2). It is also becoming increasingly clear that long-term cell volume adaptation to chronic hypotonicity through release of organic osmolytes comes at the expense of compromised organ function. This potentially explains the complications of chronic hyponatremia, including cognitive impairment, bone loss and vascular calcification. This review will illustrate why these new insights derived from basic science are also relevant for developing new approaches to treat water balance disorders.

Automating Dental Condition Detection on Panoramic Radiographs: Challenges, Pitfalls, and Opportunities.

Background/Objectives: The integration of AI into dentistry holds promise for improving diagnostic workflows, particularly in the detection of dental pathologies and pre-radiotherapy screening for head and neck cancer patients. This study aimed to develop and validate an AI model for detecting various dental conditions, with a focus on identifying teeth at risk prior to radiotherapy. Methods: A YOLOv8 model was trained on a dataset of 1628 annotated panoramic radiographs and externally validated on 180 radiographs from multiple centers. The model was designed to detect a variety of dental conditions, including periapical lesions, impacted teeth, root fragments, prosthetic restorations, and orthodontic devices. Results: The model showed strong performance in detecting implants, endodontic treatments, and surgical devices, with precision and recall values exceeding 0.8 for several conditions. However, performance declined during external validation, highlighting the need for improvements in generalizability. Conclusions: YOLOv8 demonstrated robust detection capabilities for several dental conditions, especially in training data. However, further refinement is needed to enhance generalizability in external datasets and improve performance for conditions like periapical lesions and bone loss.

Anticonvulsants impacting bone metabolism: interim results from a cross-sectional study

Background. Despite a wide range of antiepileptic drugs (AEDs) with an improved pharmacological profile, patients often experience a variety of side effects during long-trem anticonvulsant therapy, among which are osteoporotic disorders. Currently, the mechanisms of AED effect on bone metabolism remain poorly understood, which creates certain difficulties in prevention and treatment of AED-induced osteoporosis.Objective: to study bone mineral density and laboratory parameters of bone metabolism in patients with epilepsy and longterm AED administration.Material and methods. A cross-sectional study included two comparison groups: 100 adult patients with epilepsy receiving AEDs for more than 12 months and 58 healthy volunteers without taking AEDs. All participants underwent general clinical examination, computed tomography (CT) densitometry at three time points (L1, L2 and femoral neck) and laboratory tests of mineral metabolism.Results. According to CT-densitometry results, a decrease in bone mineral density was detected in the majority of participants from both study groups. While assessing an impact of osteoporosis risk factors on bone tissue in epileptic patients, low motor activity and duration of AED therapy were the most significant, which was associated with lower bone mineral density indices. The study of laboratory mineral metabolism indicators revealed significant inter-group differences in indicators such as ionized calcium, 25-hydroxy-calciferol, free thyroxine and prolactin (p(U)=0.044, p(U)=0.040, p(U)=0.001, p(U)=0.003, respectively).Conclusion. The intermediate study results showed that long-term anticonvulsant use negatively affected bone metabolism in patients suffering from epilepsy. The data obtained point at need for further in-depth study of AED therapy effect on mineral metabolism.

Association between dietary vitamin E and osteoporosis in older adults in the United States.

Increased oxidative stress due to aging can lead to increased bone loss. The most abundant form of vitamin E, namely α-tocopherol, has high antioxidant properties and biological activity; however, its effect on osteoporosis has not been well studied in humans. We aimed to investigate the association between dietary vitamin E (α-tocopherol) and osteoporosis among older adults in the United States. This cross-sectional study analyzed data on older adults in the United States aged ≥50 years from the 2007-2010, 2013-2014 and 2017-2020 pre-pandemic cycles of the National Health and Nutrition Examination Survey. Sample-weighted multivariate regression models were used, with adjustments for relevant confounders. This study comprised 5,800 individuals with available data on dietary intake and bone mineral density of hip and spine. The mean participant age was 61.4 (standard deviation, 8.7) years, and approximately 9.9% had osteoporosis. High vitamin E intake was significantly associated with a reduced risk of osteoporosis (odds ratio, 0.96, 95% confidence interval, 0.93-0.98). In addition, there was evidence of interaction between dietary vitamin E and prior fracture on preventing osteoporosis. Our study indicated a linear association between dietary vitamin E levels and osteoporosis in an older population in the United States. Further research is required to explore the potential effects of different forms of vitamin E on osteoporosis.

Men with HIV have increased alveolar bone loss

BackgroundPeriodontal health in men with HIV remains understudied, despite suggestions of associations between HIV infection and gingival pocketing, periodontal attachment loss, and gingival inflammation. As antiretroviral therapy (ART) has improved the quality of life for people living with HIV (PLWH), aging-related risk factors and comorbidities, including periodontitis, have emerged. This study aims to assess alveolar bone height, gingival crevicular fluid (GCF) cytokines, and periodontal disease activity in men with and without HIV.MethodsNinety-three men (50 HIV+, 43 HIV-) aged 35–70 years were recruited from Columbia University Irving Medical Center clinics. Periodontal examination, GCF collection, and intraoral radiographs were collected. Statistical analysis was conducted with t-tests for continuous variables and chi-squared tests for categorical variables.ResultsWhile no significant differences were observed in bleeding on probing, clinical attachment loss and pocket depths, men with HIV exhibited significantly greater alveolar crestal height on radiographs compared to men without HIV (HIV + 3.41+/-1.35 mm, HIV- 2.64+/-1.01 mm; p = 0.004), reflecting greater alveolar bone loss.ConclusionsMen living with HIV demonstrate increased alveolar bone loss compared to those without HIV, possibly mediated by elevated IL6 levels. These results underscore the importance of comprehensive oral health management in PLWH and highlight the need for further research understanding the mechanisms linking HIV infection, cytokine dysregulation, and periodontal health.

Research trends in exercise therapy for the treatment of pain in postmenopausal osteoporosis over the past decade: A bibliometric analysis.

Postmenopausal osteoporosis (PMOP) is the most common form of primary osteoporosis among women, and the associated pain often drives patients to seek clinical intervention. Numerous studies have highlighted the unique clinical benefits of exercise therapy (ET) in alleviating PMOP-related pain. However, bibliometric analyses examining collaboration, development trends, and research frontiers in the field of ET for PMOP pain remain scarce. To explore the research trends in ET for pain treatment in PMOP patients over the past decade. All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection. Utilizing the capabilities of CiteSpace 6.2.R5, we conducted a thorough analysis of publications, authors, frequently cited scholars, contributing nations, institutions, journals of significant citation, comprehensive references, and pivotal keywords. Additionally, our examination explored keyword cooccurrences, detailed timelines, and periods of heightened citation activity. This comprehensive search, from 2014 through 2023, was completed within a single day, on October 11, 2023. In total, 2914 articles were ultimately included in the analysis. There was a rapid increase in annual publication output in 2015, followed by stable growth in subsequent years. Boninger, Michael L, is the most prolific author, whereas Ware JE has the most citations. The United States' global influence is significant, surpassing all other nations. The University of California System and Harvard University are the most influential academic institutions. J Bone Joint Surg Am is the most influential journal in this field. "Spinal cord injury" is the keyword that has garnered the most attention from researchers. The developmental pattern in this field is characterized by interdisciplinary fusion, with different disciplines converging to drive progress. The academic development of the field of ET for pain in PMOP has matured and stabilized. Clinical management and rehabilitation strategies, along with the mechanisms underlying the relationship between ET and bone resorption analgesia, continue to be the current and future focal points of research in this field.

From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches.

Osteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies-genomics, transcriptomics, proteomics, and metabolomics-have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions.

HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation associated osteoporosis (PLO).

Pregnancy and lactation associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma, spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO - in comparison to both healthy premenopausal Controls (n= 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (Non-PLO IOP;n= 50). Women with PLO (aged 34 ± 6yrs) had a more severe clinical presentation than Non-PLO IOP: 80% had vertebral and 92% had multiple fractures (P<.001). They had lower DXA aBMD at all sites vs Controls (all P<.001) and non-PLO IOP (all P<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters, and lower bone strength than Controls (all P<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all P≤.01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n= 25) evaluated ≤12M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than Distant PLO (n= 34) evaluated >12M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.

Experience in using artificial intelligence services for diagnosing compression fracture of vertebral body based on computed tomography – from testing to trials

Backgraund:Osteoporosis (OP) is often diagnosed at the stage of complications. Compression fractures (CF) of the vertebral bodies, complications of OP, and predictors of subsequent fractures are often asymptomatic. CF can be detected on CT scan performed for other indications. We have analyzed approaches to using artificial intelligence services (AI services) generated for diagnosing CF of the vertebral bodies. Aims:Testing AI services to identify CF based on chest CT and to assess the possibility of their implementation into the practice of medical facilities of the Moscow Healthcare Department. Materials and methods:For setting a clinical task for AI services, basic diagnostic requirements in the direction of “Osteoporosis” are formed. AI services go through the following stages: self-testing, functional and calibration testing, trial and trial operation. The first three stages of testing are carried out on previously generated datasets. At the stages of trial and trial operation, AI services analyze CT examinations performed in medical facilities. An expert group of radiologists evaluates the diagnostic accuracy and functional capacity of AI services at all stages. The obtained quantitative metrics of the accuracy of AI services are compared with the target values ​​specified in the requirements. Results:From June 2021 to June 2022, two AI services (AI service №1 and AI service №2) which used different methods for identifying a presence of CF were tested. AI services successfully passed the self-testing stage (6), functional (5) and calibration (100) testing. The ROC AUC for AI service №1 was 0.99 and for AI service №2–0.91. The AI service №1 passed the trial stage without any significant remarks, while AI service №2 was sent for revision. After the trial operation stage, the following accuracy metrics were obtained: the ROC AUC for AI service №1 was 0.93; for AI service №2–0.92. At all stages, both AI services showed sufficient metrics for clinical validation. Conclusions:A testing of the performance of AI services in the direction of “Osteoporosis” was carried out. A high quality of diagnosis was demonstrated. AI services can act as an auxiliary tool in the medical decision support system.

The effect of body mass index on bone density by age distribution in women.

Osteoporosis significantly affects public health, especially among postmenopausal women, by reducing bone mass and increasing the risk of fractures. While the influence of body mass index (BMI) on Bone Mineral Density (BMD) is acknowledged, the specific age range in which BMI most significantly affects bone density remains unclear. This study aims to explore the relationship between BMI and BMD in different age groups to identify potential age-specific risk factors for osteoporosis. In a retrospective cohort study at the University of Health Sciences Turkey, X Hospital, DXA scans of 240 postmenopausal women aged 40 to 80 were analyzed between February 2018 and February 2020. The study used statistical analyses, including ANCOVA and Pearson correlation, to investigate the effects of BMI on BMD, adjusting for age and other variables. Analysis revealed a complex interaction between BMI and BMD. Controlling for BMI showed a statistically significant difference in measurements of lumbar T, neck T, and trochanter T between age groups (P < .05). Specifically, bone density in the 40 to 49 age range was found to be lower when adjusted for BMI, suggesting that the protective effect of higher BMI is less pronounced in younger postmenopausal ages but decreases less negatively in older groups. The impact of BMI on trochanter T measurements was markedly different, increasing in the 40 to 49 age group, while decreasing in others. BMI, along with body weight and age, are important determinants of BMD, but not the sole factors influencing bone loss. The study highlights the need for a personalized approach to osteoporosis risk, considering a broader spectrum of genetic, hormonal and lifestyle factors. It recommends further evaluation of other risk factors in larger cohorts and emphasizes the importance of future longitudinal research to elucidate the dynamic relationship between BMI and BMD over time.

An Insight of Plant Source, Toxicological Profile, and Pharmacological Activities of Iridoid Loganic Acid: A ComprehensiveReview.

This study evaluates the pharmacological effects of iridoid glucoside loganic acid, a plant constituent with diverse properties, based on literature, and explores the underlying cellular mechanisms for treating several ailments. Data were collected from reliable electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, etc. The results demonstrated the anti-inflammatory, anti-oxidant, and other protective effects of loganic acid on metabolic diseases and disorders such as atherosclerosis, diabetes, and obesity, in addition to its osteoprotective and anticancer properties. The antioxidant activity of loganic acid demonstrates its capacity to protect cells from oxidative damage and mitigates inflammation by reducing the activity of inflammatory cytokines involving TNF-α and IL-6, substantially upregulating the expression of PPAR-γ/α, and decreasing the clinical signs of inflammation-related conditions related to hypertriglyceridemia and atherosclerosis. Meanwhile, loganic acid inhibits bone loss, exhibits osteoprotective properties by increasing mRNA expression levels of bone synthesizing genes such as Alpl, Bglap, and Sp7, and significantly increases osteoblastic proliferation in preosteoblast cells. Loganic acid is an anti-metastatic drug that reduces MnSOD expression, inhibits EMT and metastasis, and prevents cellular migration, proliferation, and invasion in hepatocellular carcinoma cells. However, additional clinical trials are required to assess its safety, efficacy, and human dose.

No genetic causal relationship between lung function and osteoporosis ― evidence from a mendelian randomization study

For a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level. To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran’s Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy. In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the. results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors.

A Clinical Evaluation of the Role of Autoimmunity in the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis.

Background/objectives: Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. Methods: Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. Results: A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ -2.5. A higher erosion score was associated with a lower BMD (value: -0.222; p = 0.009) and T-score (value -0.397; p < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04)). ACPA titers were associated with a lower BMD in the hip (value -0.216; p = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. Conclusions: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening.

Associations of AMH in mid-reproductive years with bone mineral density and turnover markers in mid-life.

Concentration of circulating anti-Müllerian hormone (AMH) predicts short-term (3-5 years) bone loss around menopause. Whether AMH during mid-reproductive years predicts bone health over a decade later is unknown. To study the association of AMH levels in mid-reproductive years with bone density and turnover biomarkers measured after ∼14 years of follow-up. We assessed plasma AMH in 2003-2006 (mean 37.0 years, SD 5.1) among 450 parous women (71% White) in a US longitudinal cohort, and bone mineral density (BMD; spine, hip, and femoral neck, measured by dual-energy X-ray absorptiometry) in 2017-2021 (mean 51.0 years, SD 5.1). Secondary outcomes were plasma levels of procollagen type I N-propeptide (PINP) and C-terminal telopeptide I (CTX-I). In linear regression models adjusted for demographics and lifestyle, compared to women with AMH >3.5 ng/mL, those with AMH <1.0 ng/mL had lower BMD (g/cm2) at follow-up (beta [95% CI]: spine: -0.06 [-0.10, -0.02]; hip: -0.05 [-0.08, -0.02]; femoral neck: -0.03 [-0.06, 0.00]) and higher bone turnover markers (beta [95% CI]: PINP: 0.36 SD [0.10, 0.63]; CTX-I: 0.34 SD [0.07, 0.60]). The association of AMH with spine BMD was more pronounced among post-menopausal women, in contrast to associations with bone turnover markers which were more pronounced among women who had not yet reached menopause. The associations between AMH and BMD were primarily mediated by menopausal status at follow-up. Lower AMH during mid-reproductive years is associated with lower BMD and higher bone turnover 14 years later. Ovarian reserve during mid-reproductive years may be a valuable predictor of long-term bone health.

Puerarin alleviates osteoporosis in rats by targeting the JAK2/STAT3 signaling pathway.

Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.

Wharton's jelly of the umbilical cord serves as a natural biomaterial to promote osteogenesis.

Various factors can contribute to bone damage or loss, presenting challenges for bone regeneration. Our study explores the potential clinical applications of two processed forms of Wharton's jelly of the human umbilical cord for treating bone loss. Wharton's jelly from fresh umbilical cords underwent two distinct processes: (1) frozen Wharton's jelly (WJF), preserved with cryoprotective agents, and (2) decellularized Wharton's jelly matrix (WJD), prepared only via lyophilization without cryoprotectants. Both WJD and WJF are rich in collagen, hyaluronan, and polysaccharide proteins. Notably, WJD exhibited a porous structure lacking nuclei from human umbilical cord mesenchymal stem cells, unlike WJF. In direct contact experiments, WJD stimulated osteoblast migration, enhanced osteoblast maturation, and promoted calcium deposition for bone formation when administered to cultured rat osteoblasts. Furthermore, in transwell co-culture experiments, both WJD and WJF increased the rat osteoblast expression of RUNX2 and OPN genes, elevated alkaline phosphatase levels, and enhanced extracellular calcium precipitation, indicating their role in osteoblast maturation and new bone formation. Hyaluronic acid, one of the ingredients from WJD and WJF, was identified as a key component triggering osteogenesis. In vivo experiments involved creating circular bone defects in the calvarias of rats, where WJD and WJF were separately implanted and monitored over five months using micro-computerized tomography. Our results demonstrated that both WJD and WJF enhanced angiogenesis, collagen formation, osteoblast maturation, and bone growth within the bone defects. In summary, WJD and WJF, natural biomaterials with biocompatibility and nontoxicity, act not only as effective scaffolds but also promote osteoblast adhesion and differentiation, and accelerate osteogenesis.