Fracture Risk Research Articles

Segmentation methods for quantifying X-ray Computed Tomography based biomarkers to assess hip fracture risk: a systematic literature review.

The success of using bone mineral density and/or FRAX to predict femoral osteoporotic fracture risk is modest since they do not account for mechanical determinants that affect bone fracture risk. Computed Tomography (CT)-based geometric, densitometric, and finite element-derived biomarkers have been developed and used as parameters for assessing fracture risk. However, to quantify these biomarkers, segmentation of CT data is needed. Doing this manually or semi-automatically is labor-intensive, preventing the adoption of these biomarkers into clinical practice. In recent years, fully automated methods for segmenting CT data have started to emerge. Quantifying the accuracy, robustness, reproducibility, and repeatability of these segmentation tools is of major importance for research and the potential translation of CT-based biomarkers into clinical practice. A comprehensive literature search was performed in PubMed up to the end of July 2024. Only segmentation methods that were quantitatively validated on human femurs and/or pelvises and on both clinical and non-clinical CT were included. The accuracy, robustness, reproducibility, and repeatability of these segmentation methods were investigated, reporting quantitatively the metrics used to evaluate these aspects of segmentation. The studies included were evaluated for the risk of, and sources of bias, that may affect the results reported. A total of 54 studies fulfilled the inclusion criteria. The analysis of the included papers showed that automatic segmentation methods led to accurate results, however, there may exist a need to standardize reporting of accuracy across studies. Few works investigated robustness to allow for detailed conclusions on this aspect. Finally, it seems that the bone segmentation field has only addressed the concept of reproducibility and repeatability to a very limited extent, which entails that most of the studies are at high risk of bias. Based on the studies analyzed, some recommendations for future studies are made for advancing the development of a standardized segmentation protocol. Moreover, standardized metrics are proposed to evaluate accuracy, robustness, reproducibility, and repeatability of segmentation methods, to ease comparison between different approaches.

Mediterranean Diet and Risk of Hip Fracture: A Systematic Review and Dose-Response Meta-Analysis.

Hip fractures are a major public health concern. Understanding their epidemiologic and biological links with diet and cardiovascular risk may have important implications for prevention. To assess the dose-response association of Mediterranean diet (MD) adherence with the risk of hip fracture. A systematic search was conducted in the PubMed, Scopus, and Web of Science databases for prospective studies. Search terms were "Mediterranean Diet" and "Fracture." Data were extracted from 8 studies, encompassing 15 cohorts that included 503 174 individuals. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies of Interventions. The "meta" and "dosresmeta" packages were used in R Studio Software. The results demonstrated that high and moderate MD adherence were associated with a reduced risk of hip fracture (relative risk [RR] = 0.71 [95% CI, 0.55-0.91]; and RR = 0.78[(95% CI, 0.65-0.93], respectively). The effect of the association was similar in men and women. The dose-response pattern of the association was linear: each point increase in MD adherence was associated with a 5.25% reduction in hip fracture risk. Adherence to MD is associated with a reduction in hip fracture risk, following a linear dose-response pattern. This supports the promotion of this dietary pattern for improving bone health. PROSPERO registration no. CRD42023402284.

Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.

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.

The essential role of combined calcium and vitamin D supplementation in the osteoporosis scenario in italy: Expert opinion paper

SummaryAn Italian multidisciplinary working group discussed the current Italian scenario of osteoporosis management during a meeting and highlighted the essential role of calcium and vitamin D supplementation in the prevention of fragility fractures.PurposeThis paper aims to review and discuss data on calcium and vitamin D requirements and the role of combined calcium and vitamin D supplementation in the treatment of patients with osteoporosis.MethodsThe discussion of the experts covered literature data on calcium and vitamin D supplementation, gaps in the diagnosis and treatment of osteoporosis, and the role of the primary care physician in identifying and treating patients with osteoporosis. Articles for consideration were identified through PubMed searches using different combinations of pertinent keywords.ResultsThe discussion highlighted that insufficient calcium or vitamin D intake increases the risk of fragility fractures. The experts also drew attention to the essential role of calcium and vitamin D supplementation in achieving an anti-fracture effect and supporting the efficacy of anti-osteoporotic agents without increasing nephrolithiasis and cardiovascular risks. In addition, the discussion underlined the role of the primary care physician in the initial clinical approach to patients with osteoporosis.ConclusionsThe experts believe that efficient treatment for patients with osteoporosis should include calcium and vitamin D supplementation to achieve adequate levels that are able to inhibit the parathyroid hormone and bone resorption.

Complications associated with the removal of totally implantable venous access devices (TIVADs): a retrospective analysis of 4,954 breast cancer patients in a single institution

BackgroundTotally implantable venous access devices (TIVADs) have been widely used for many years in the management of cancer patients. However, previous studies have rarely focused on the period surrounding TIVAD removal, which is a critically important phase for these devices. This study aims to address this gap by investigating the surgical approaches, timing, and associated complications related to the removal of TIVADs, thereby enhancing the management of these devices.MethodA retrospective analysis was conducted on a cohort of 4,954 TIVAD extraction procedures performed at the Breast Center of the Fourth Hospital of Hebei Medical University between January 1, 2016, and August 1, 2023.ResultsAmong 4,954 cases, the indwelling time of TIVADs for included patients ranged from 2 to 60 months. 4,882(98.5%) cases removed their TIVADs after completion of cancer treatment, while 72 cases (1.5%) were unplanned removal due to TIVADs related complications. Two surgical techniques were observed for port removal: in 20% of cases, the injection port was removed first, followed by the catheter; in 80% of cases, the catheter was removed first, followed by the injection port. Complications during TIVADs removal were observed in 13 cases (0.3%) including 2 cases of bleeding, 5 cases difficulty in removal of the port and catheter, and 6 cases representing of delayed wound healing. Longer indwelling time tended to have higher risk of developing catheter rupture and fracture.ConclusionThis study provides valuable insights into the removal of TIVADs in cancer patients. Complications during removal were uncommon but included bleeding, difficulty in removing the port and catheter, and delayed wound healing. Additionally, longer indwelling times were associated with an increased risk of catheter rupture and fracture, highlighting the need for careful monitoring and timely removal of TIVADs to minimize potential complications. The findings of the study underscore the importance of optimizing TIVAD management, particularly during the removal phase, to improve patient outcomes.

Cost-effectiveness analysis of denosumab versus alendronate for improving bone mineral density in renal transplant recipients: a comparative study

BackgroundDenosumab and alendronate had a positive impact on bone mineral density (BMD) preservation after kidney transplantation. However, the cost-effectiveness of these agents in the context of kidney transplantation remains largely unexplored. We have conducted a cost-effectiveness analysis to compare the cost and the clinical outcomes of adding subcutaneous (SC) 60 mg denosumab every 6 months vs. oral weekly 70 mg Alendronate, to the standard care therapy (vitamin D and calcium) in renal transplant recipients (RTRs). The impact of both drugs on BMD t-score improvement and fracture prevention was investigated. A decision-analysis model from a health care payer perspective was applied.ResultsThe cost-effectiveness analysis has shown that alendronate add-on to the standard therapy was the most cost-effective regimen, in terms of BMD improvement and fracture prevention with an incremental cost-effectiveness ratio (ICER) of $154/patient/year. The one-way sensitivity analyses have delineated the change in cost-effectiveness when alendronate retail unit price was increased by 25% and 50%, or when denosumab retail unit price was decreased by 25% and 50%. The model was sensitive to the uncertainties (95% confidence interval) in the probabilities of fracture prevention and the probabilities of attaining the desired outcome.ConclusionThe model suggests that oral once weekly alendronate add-on regimen to standard therapy seems to be substantially more cost effective than twice yearly SC denosumab in terms of BMD improvement and fracture prevention in RTRs. Longer time horizon models with longer follow-up periods for fracture risks and adverse events are warranted to validate these data.

Identification of osteoporosis genes using family studies.

Osteoporosis is a multifactorial bone disease characterised by reduced bone mass and increased fracture risk. Family studies have made significant contribution in unravelling the genetics of osteoporosis. Yet, most of the underlying molecular and biological mechanisms remain unknown prompting the need for further studies. This review outlines the proper phenotyping and advanced genetic techniques in the form of high-throughput DNA sequencing used to identify genetic factors underlying monogenic osteoporosis in a family-based setting. The steps related to variant filtering prioritisation and curation are also described. From an evolutionary perspective, deleterious risk variants with higher penetrance tend to be rare as a result of negative selection. High-throughput sequencing (HTS) can identify rare variants with large effect sizes which are likely to be missed by candidate gene analysis or genome-wide association studies (GWAS) wherein common variants with small to moderate effect sizes are identified. We also describe the importance of replicating implicated genes, and possibly variants, identified following HTS to confirm their causality. Replication of the gene in other families, singletons or independent cohorts confirms that the shortlisted genes and/or variants are indeed causal. Furthermore, novel genes and/or variants implicated in monogenic osteoporosis require a thorough validation by means of in vitro and in vivo assessment. Therefore, analyses of families can continue to elucidate the genetic architecture of osteoporosis, paving the way for improved diagnostic and therapeutic strategies.

Rapid reduction in fracture risk after the discontinuation of long-term oral glucocorticoid therapy: a retrospective cohort study using a nationwide health insurance claims database in Japan.

We investigated changes in fracture risk following discontinuation of long-term oral glucocorticoids (GCs) using Japan's nationwide health insurance claims database (NDBJ). We identified patients aged ≥ 50 years who initiated GC therapy in 2012-2019. Those receiving ≥ 5mg (prednisolone or equivalent, PSL)/day for ≥ 72days in the initial 90days of GC therapy were classified as the GC-exposure group, and those receiving < 5mg PSL/day for < 30days were classified as the reference group. Patients discontinuing GC after 90days of GC therapy were classified as the GC-discontinuation group; all others were classified as the GC-continuation group. We tracked the incidence rates of hip and clinical vertebral fractures for up to 990days, and assessed fracture risk after GC discontinuation by hazard ratios (HR) adjusted by inverse probability weighting using propensity scores for GC discontinuation. There was a total of 52,179 GC-discontinuation, 91,969 GC-continuation, and 43,138 reference group women, and 57,560, 93,736, and 33,696 men in the corresponding groups, respectively. According to adjusted HRs, incidence rates of fractures were significantly lower in the GC-discontinuation group than in the GC-continuation group in the initial 90days after GC discontinuation and remained significant for 360days, except for hip fracture in men. HRs for hip fractures remained significantly higher in the GC-discontinuation group compared to the reference group for 720days post-discontinuation. Fracture risk declines rapidly in the first year after GC discontinuation, but vigilance is necessary as the increased risk persists for two years post-discontinuation.

Applying 3D-Printed Porous Ti6Al4V Prostheses to Repair Osteomyelitis-Induced Partial Bone Defects of Lower Limbs: Finite Element Analysis and Clinical Outcomes.

The clinical management of partial bone defects in lower limbs, particularly those resulting from osteomyelitis, remains a significant challenge. This study aimed to systematically evaluate the effectiveness of 3D-printed porous Ti6Al4V prostheses in addressing osteomyelitis-induced partial bone defects. We established a comprehensive protocol for utilizing 3D-printed prostheses for bone defect repair, encompassing 3D simulation of prosthesis implantation and internal fixation, finite element analysis (FEA), and clinical implementation. Mimics software facilitated simulation of fixation patterns and screw lengths. FEA modeled bone defects in the distal metaphyseal femur and distal diaphyseal tibia to assess changes in stress conduction pre- and post-prosthesis implantation. The clinical study involved eight patients (average age: 56.3 years) with an average defect length of 14.9 cm. Postoperative outcomes were evaluated using X-rays and the Lower Extremity Functional Scale (LEFS). FEA demonstrated that the implanted prostheses effectively shared stress and reduced the load on residual bone in both models, thus lowering the risk of fractures under external forces. The average follow-up period was 24.5 months, with patients initiating weight-bearing activities on average 7.8 days post-surgery. Serial postoperative X-rays demonstrated long-term stability of the prostheses, with progressive bone regeneration around and integration with the prostheses. While two patients experienced infection recurrence requiring prosthesis removal and debridement, the remaining six showed significant improvement in LEFS scores, increasing from 31.5 preoperatively to 61.0 at the last follow-up. 3D-printed porous Ti6Al4V prostheses effectively restore anatomical integrity and optimize stress conduction in lower limbs, resulting in substantial functional recovery. This innovative approach shows promise for wider clinical adoption and warrants further investigation in medical practice.

Clinical and demographic factors determining patient fracture risk decision point (FRDP): The improving risk communication in osteoporosis (RICO) project.

This part of the Improving Risk Communication in Osteoporosis (RICO) study aims to understand patients' willingness to initiate osteoporosis treatment given a hypothetical fracture probability-derived from the FRAX® Risk Assessment Tool-and how age, fracture history, and numeric literacy may influence this. In 2022-2023, 332 postmenopausal women at risk of fracture were interviewed from nine countries to determine participants' Fracture Risk Decision Point (FRDP), the lowest probability of major osteoporotic fracture at which they would accept an osteoporosis medication. Participants' FRDP was evaluated given eight hypothetical 10-year FRAX scores. In countries with FRAX-based treatment thresholds, over half of the participants per country reported an FRDP that was below the threshold. Collectively, 79.2% demonstrated FRDPs at or below their respective threshold. Age and fracture history did not have a strong influence on FRDP; however, those who demonstrated higher levels of numeric literacy reported a significantly higher median FRDP (10%) compared to those who showed lower levels (5%, p < 0.001). Most patients were willing to accept an osteoporosis medication prescription at a hypothetical FRAX probability that was even lower than that of their nationally recommended treatment threshold. Literacy scores had a significant influence on FRDP whereas age and fracture history did not.

Hip arthroplasty following failure of internal fixation in intertrochanteric femoral fractures: classification decision-making for femoral stem selection and clinical validation

AimsFollowing Failed Internal Fixation of Intertrochanteric Fractures (FIF-ITF), the choice of treatment remains a clinical challenge. This study introduces a novel classification system to guide the selection of femoral prostheses in hip arthroplasty (HA) and validates its clinical efficacy.MethodsRetrospectively, we analyzed 108 cases from three university-affiliated hospitals between December 2012 and February 2023 involving patients who underwent hip arthroplasty due to Failed Internal Fixation of Intertrochanteric Fractures (FIF-ITF). Patients were classified into three categories based on fracture healing, proximal femoral support, and the severity of femoral cortical defects, with subtypes identified. Surgical outcomes and complication rates were compared between the Classification-based Decision Group and the Non-classification Decision Group.ResultsThe Classification-based Decision Group did not differ significantly from the Non-classification Decision Group in operation time, blood loss, or the use of cemented stems. However, the classification system markedly reduced the risk of periprosthetic fractures intraoperatively from 22.5 to 4.4% and postoperatively from 10 to 1.4%. The Classification-based Decision Group also demonstrated higher postoperative Harris Hip Score (HHS) and Visual Analog Scale (VAS) scores.ConclusionThe proposed classification system serves as an innovative clinical tool for femoral prosthesis selection in hip arthroplasty post-FIF-ITF, effectively reducing complications and enhancing hip function in the Classification-based Decision Group, underscoring its significant clinical utility.

Renal Function Is Associated with Changes in Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Denosumab: Data From a Retrospective Cohort Study.

Background/Objectives: Renal function influences bone metabolism, as kidney failure can increase the risk of fractures. Denosumab is an approved osteoporosis treatment, but its efficacy in relation to renal function has not yet been studied in real-life scenarios. This study aimed to investigate the denosumab-induced change in bone mineral density (BMD) according to kidney function. Methods: A retrospective analysis was conducted at the outpatient clinic in postmenopausal women receiving denosumab (60 mg subcutaneously administered every 6 months). The glomerular filtration rate (eGFR) was measured by the 2021 CKD-EPI equation and patients were stratified for eGFR categories. BMD was measured by dual-energy X-ray absorptiometry. Results: 128 women (mean age 70.3 ± 9.4 years) were recruited. The mean denosumab treatment duration was 3.9 ± 1.4 years and all the participants had improved BMD values. In stepwise multiple regression analysis-after controlling for age, BMI, and treatment duration-the eGFR value (ß = -0.11, SE 0.04, p = 0.01) was independently associated with the lumbar spine BMD change. The same association remained when the eGFR categories were considered (ß = 3.564, SE 1.29, p = 0.007). In addition, after controlling for BMI and the duration of denosumab treatment, age (ß = -0.7915, SE 0.37, p = 0.03) and eGFR (ß = -0.3257, SE 0.1567, p = 0.04) were found to be associated with femoral neck BMD change. The association remained when considering eGFR categories (ß = 8.7339, SE 4.29, p = 0.04). Conclusions: This retrospective study suggests that eGFR is associated with denosumab efficacy in postmenopausal women treated for osteoporosis.

Numerical search for the effective thermal conductivity of cracked media

Spacecraft parts accumulate damage during operation and defects that are invariably present even in new designs may grow. This leads to changes in the behavior of individual parts of the space vehicle and, consequently, to the risk of fracture. A more accurate assessment of spacecraft safety requires internal defects to be included in the material models under consideration. One of the main hazardous effects on space objects is multiple temperature heating and cooling due to periodic action of solar rays. This paper presents a study of thermal conduction of media containing cracks. It is carried out with the help of a technique developed by the authors to determine the effective thermal conductivity of materials and based on approximate numerical solution of the steady-state thermal conduction problem for a three-dimensional medium with cracks by the boundary element method. This technique allows to obtain the distribution of the temperature field and heat flux density at any point of the body under consideration, as well as to calculate the effective parameters of materials with high accuracy at relatively low calculation time using ordinary personal computers of average power. The basis of the numerical method presented in this paper is the decomposition of the desired solution into a series of some pre-calculated analytical solutions of the heat conduction equations. The dependence of the effective thermal conductivity on the density of thermally insulated cracks was considered. The formula of this dependence is proposed. Verification of the proposed methodology was carried out by comparing the numerical results of a number of problems with the results of other authors.

Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions.

Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

Evaluating the Predictive Power of Frailty and Bone Mineral Density on Fracture Risk in Rural Older Adults.

Evaluating the Predictive Power of Frailty and Bone Mineral Density on Fracture Risk in Rural Older Adults.

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.

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.

Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect.

Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1-34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11+ cells expressed high levels of Mmp13, Limch1, and Wif1, confirming their osteoprogenitor status. ISH confirmed co-expression of Mmp13 and Tnfsf11 in bone surface cells of both vehicle- and OPG:Fc-treated mice. Under physiological conditions of human/mouse bone, RANKL is expressed mainly by osteoprogenitors proximate to the osteoclasts, while OPG is expressed mainly by osteocytes and bone-forming osteoblasts.

Risk of fracture in users of hormonal contraception.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of hormonal contraception used for pregnancy prevention on fracture risk in individuals who are currently or were previously capable of becoming pregnant.