Decreased Bone Mineral Density Research Articles

Features of Bone Mineral Density, Calcium-Phosphorus Metabolism and Bone Remodeling in Patients with Systemic Lupus Erythematosus

Introduction. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations associated with multiple autoantibodies formation and deposition of immune complexes, and other immune processes. Despite significant advances in treatment, the disease remains disabling, in particular, due to increased bone fragility and low-energy fractures. The study of bone remodeling in patients with SLE should help to improve the therapy and quality of their treatment. The aim of the study. To investigate the features of bone mineral density, calcium-phosphorus metabolism and bone remodeling in patients with systemic lupus erythematosus. Materials and methods. The study involved 123 women with SLE aged 21-51 years. The comparison group (CG) consisted of 25 women without SLE in premenopausal status of the appropriate age. The control group included 25 practically healthy women. In order to study bone mineral density (BMD), dual-energy X-ray densitometry (DXA) of the lumbar spine was performed using a dual-energy X-ray absorptiometer. For the study of calcium-phosphorus metabolism (CPM), total calcium (Ca), ionized Ca, phosphorus (P) in blood and Ca, P, creatinine in daily urine, as well as parathyroid hormone (PTH) and 25-hydroxyvitamin D in serum were determined. Markers of bone remodeling (osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP) and isomerized C-terminal telopeptide (β-crosslaps) in serum were measured. To achieve the stated goal, the first step included the determination of bone damage prevalence in patients with the diagnosed SLE; the second step was directed towards the characterization the particular bone condition in patients with SLE based on the results of BMD, CPM indices and markers of bone remodeling assessment. Results and discussion. According to the results of DXA of the lumbar spine, 88 (71.54 %) women of the SG and only 8 (32.00 %) women of the CG had a decrease in BMD (p < 0.001). According to the mean values, the studied CPM indices of the SG patients, CG and control group wemen exposed no significant differences. Similarly, no significant differences were detected in the mean values of urinary phosphorus and in between blood PTH values in SG, CG, and control. The level of 25-hydroxyvitamin D was significantly lower in SG (15.14 ± 0.80 ng/ml) than in CG (19.62 ± 0.46 ng/ml) and control (22.38 ± 1.34 ng/ml) p < 0.05. The mean value of osteocalcin in woman with SLE was significantly lower than in CG and control (11.81 ± 0.49 ng/ml versus 18.61 ± 0.75 ng/ml and 19.28 ± 1.88, p < 0.001). No significant difference were detected in between the mean values of P1NP in SG, CG and control. The mean values of β-cross laps were significantly higher in patients with SLE (0.51 ± 0.02 ng/ml) compared to GC (0.26 ± 0.02 ng/ml) and control (0.28 ± 0.02 ng/ml), p < 0.001. Conclusions. Bone mineral density, calcium-phosphorus metabolism and bone remodeling in patients with systemic lupus erythematosus have peculiarities as follows: a significant decrease in bone mass in 71.54 % of patients, namely 18, 70 % - grade I osteopenia, 21.14 % - grade II osteopenia, 14.63 % - grade III osteopenia; 17.07 % - osteoporosis, increased calcium excretion, vitamin D deficiency, decreased osteoblastic and enhansed osteoclastic functions.

Are Radiographic Changes in the Mandibular Canal Associated With Bone Mineral Density?

Osteoporosis, highly prevalent among postmenopausal women, significantly reduces bone density and increases the risk of fractures. Cortical bone, which constitutes the largest calcium deposit in the human skeleton, is primarily affected in various conditions, including osteoporosis. Due to its visibility in panoramic radiography, the cortical area of the mandibular canal could be valuable in assessing decreases in bone mineral density (BMD). The study aimed to characterize and compare changes in the cortices of the mandibular canal between normal, osteopenic, and osteoporotic postmenopausal women. Our cross-sectional study analyzed postmenopausal patients. We included only patients with panoramic radiographs with good quality and who underwent osteoporosis risk assessment by dual-energy x-ray absorptiometry (DXA). BMD was measured by DXA at 3 sites (spine, femur, and forearm) and used to classify the patients into normal, osteopenic, or osteoporotic. This classification remained consistent across all measurement sites. The main outcome variable was BMD of the mandibular canal cortices measured using black pixel intensity. Demographic covariates, including age, weight, height, and BMD, were assessed. One-way analysis of variance between groups considering a P<.05. The relationship between covariates and dependent variables was assessed using the Pearson correlation test. The sample comprised 52 postmenopausal women aged more than 40 years (mean age 61±10years), 26 (50%) normal, 18 (35%) osteopenic, and 8 (15%) osteoporotic. Significant differences were observed in the percentage of black pixels in the mandibular ramus between the groups. In this region, the average percentage of black pixels was 3.19% (± 0.65) for the normal group, 2.78% (±0.65) for the osteopenia group, and 2.35% (± 0.65) for the osteoporosis group (P=.015). No significant differences were found in other mandibular regions. Our findings demonstrate an association between BMD assessed in the mandibular canal cortex and the presence of osteoporosis as determined by DXA. While the observed differences in black pixel percentages in the mandibular ramus are minor, they are statistically significant, suggesting that panoramic radiography may serve as an adjunctive tool for osteoporosis screening.

Disparities in Osteoporosis Prevention and Care: Understanding Gender, Racial, and Ethnic Dynamics.

Osteoporosis, the most prevalent metabolic bone disease, significantly impacts global public health by increasing fracture risks, particularly among post-menopausal women and the elderly. Osteoporosis is characterized by decreased bone mineral density (BMD) and deterioration of bone tissue, which leads to enhanced fragility. The disease is predominantly diagnosed using dual X-ray absorptiometry (DXA) and is significantly influenced by demographic factors such as age and hormonal changes. This chapter delves into the condition's complex nature, emphasizing the pervasive gender and racial disparities in its screening, diagnosis, and treatment. Recent findings highlight a substantial gap in the management of osteoporosis, with many individuals remaining under-screened and under-treated. Factors contributing to this include the asymptomatic early stages of the disease, lack of awareness, economic barriers, and inconsistent screening practices, especially in under-resourced areas. These challenges are compounded by disparities that affect different genders and races unevenly, influencing both the prevalence of the disease and the likelihood of receiving adequate healthcare services. The summary of this chapter underscores the urgent need for targeted strategies to overcome these barriers and improve health equity in osteoporosis care. Proposed strategies include enhancing public and healthcare provider awareness of osteoporosis, broadening access to diagnostic screenings, and integrating personalized treatment approaches. These efforts aim to align with global health objectives to mitigate the impacts of osteoporosis and ensure equitable health outcomes across all demographic groups.

Clinical use of quantitative computed tomography to evaluate the effect of less paraspinal muscle damage on bone mineral density changes after lumbar interbody fusion.

A retrospective cohort study. This study aimed to assess the reliability of quantitative computed tomography (QCT) in measuring bone mineral density (BMD) of instrumented vertebrae and investigate the effect of less paraspinal muscle damage on BMD changes after lumbar interbody fusion. Patients always experience a decrease in vertebral BMD after lumbar interbody fusion. However, to the best of our knowledge, no study has analyzed the effect of paraspinal muscles on BMD changes. This retrospective analysis included a total of 155 patients who underwent single-level lumbar fusion, with 81 patients in the traditional group and 74 patients in the Wiltse group (less paraspinal muscle damage). QCT was used to measure the volumetric BMD (vBMD), Hounsfield unit value, and cross-sectional area of the paraspinal muscles at the upper instrumented vertebrae (UIV), vertebrae one segment above the UIV (UIV+1), and the vertebrae one segment above the UIV+1 (UIV+2). Statistical analyses were performed. No significant differences in general data were observed between the two groups (p>0.05). Strong correlations were noted between the preoperative and 1-week postoperative vBMD of each segment (p<0.01), with no significant difference between the two time points in both groups (p>0.05). Vertebral BMD loss was significantly higher in UIV+1 and UIV+2 in the traditional group than in the Wiltse group (-13.6%±19.1% vs. -4.2%±16.5%, -10.8%±20.3% vs. -0.9%±37.0%; p<0.05). However, no statistically significant difference was observed in the percent vBMD changes in the UIV segment between the two groups (37.7%±70.1% vs. 36.1%±78.7%, p>0.05). QCT can reliably determine BMD in the instrumented spine after lumbar interbody fusion. With QCT, we found that reducing paraspinal muscle destruction through the Wiltse approach during surgery can help preserve the adjacent vertebral BMD; however, it does not help increase the BMD in the instrumented vertebrae.

Global Trends in Research of Programmed Cell Death in Osteoporosis: A Bibliometric and Visualized Analysis (2000-2023).

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

Treatment of spinal lesions in breast cancer patients (literature review)

Breast cancer is one of the most significant problems in oncology. This pathology is characterized by increased risk of fractures associated with postmenopausal decrease in bone mineral density, use of hormone therapy, and presence of osteolytic metastases in the spine. All these factors can cause non-traumatic spine fractures decreasing patient mobility and leading to permanent pain syndrome and neurologic deficit.The article presents the modern view on the osteoporosis problem and risk of non-traumatic spine fractures in patients with breast cancer and spine metastases. Literature data on predictors of pathological bone fractures, as well as time and risk of spine metastases in these patients are analyzed. Data of modern studies on the effectiveness of various methods of breast cancer treatment and their combinations, as well as possibilities of minimally invasive surgical interventions, antiresorptive and radiological therapy are considered.

Deep learning for osteoporosis screening using an anteroposterior hip radiograph image.

Osteoporosis is a common bone disorder characterized by decreased bone mineral density (BMD) and increased bone fragility, which can lead to fractures and eventually cause morbidity and mortality. It is of great concern that the one-year mortality rate for osteoporotic hip fractures could be as high as 22%, regardless of the treatment. Currently, BMD measurement is the standard method for osteoporosis diagnosis, but it is costly and requires special equipment. While a plain radiograph can be obtained more simply and inexpensively, it is not used for diagnosis. Deep learning technologies had been applied to various medical contexts, yet few to osteoporosis unless they were trained on the advanced investigative images, such as computed tomography. The purpose of this study was to develop a deep learning model using the anteroposterior hip radiograph images and measure its diagnostic accuracy for osteoporosis. We retrospectively collected all anteroposterior hip radiograph images of patients from 2013 to 2021 at a tertiary care hospital. The BMD measurements of the included patients were reviewed, and the radiograph images that had a time interval of more than two years from the measurements were excluded. All images were randomized using a computer-generated unequal allocation into two datasets, i.e., 80% of images were used for the training dataset and the remaining 20% for the test dataset. The T score of BMD obtained from the ipsilateral femoral neck of the same patient closest to the date of the performed radiograph was chosen. The T score cutoff value of - 2.5 was used to diagnose osteoporosis. Five deep learning models were trained on the training dataset, and their diagnostic performances were evaluated using the test dataset. Finally, the best model was determined by the area under the curves (AUC). A total of 363 anteroposterior hip radiograph images were identified. The average time interval between the performed radiograph and the BMD measurement was 6.6months. Two-hundred-thirteen images were labeled as non-osteoporosis (T score > - 2.5), and the other 150 images as osteoporosis (T score ≤ - 2.5). The best-selected deep learning model achieved an AUC of 0.91 and accuracy of 0.82. This study demonstrates the potential of deep learning for osteoporosis screening using anteroposterior hip radiographs. The results suggest that the deep learning model might potentially be used as a screening tool to find patients at risk for osteoporosis to perform further BMD measurement.

Osteosarcopenia in women with rheumatoid arthritis: association with nutritional status and physical condition

Objective: to evaluate nutritional status, muscle strength, functional status of skeletal muscles and physical activity (PHA) and their relationship with the osteopenic body composition phenotype in women in post menopause with rheumatoid arthritis (RA). Material and methods. The case-control study included 134 women in post menopause with RA, 52 of them had osteosarcopenia (OSP) according to densitometry and 82 had no decrease in bone mineral density (BMD) and muscle mass (mean age 62.0 ± 7.2 and 59.6 ± 7.5 years, respectively; p &gt; 0.05). A clinical and laboratory examination as well as tests to assess muscle strength and functional status were performed. The MNA-SF and IPAQ questionnaires were used to determine nutritional status and physical activity. Results and discussion. Malnutrition was found in 51.9 % of patients, and low and average levels of PHA were found in 5.8 and 50.0 % of patients with OSP, respectively. Factors associated with OSP were identified: nutritional status according to MNA-SF &lt; 12 points (odds ratio, OR 2.52; 95 % confidence interval, CI 1.10–5.77; p = 0.029), dietary calcium intake &lt; 500 mg/day (OR 3.23; 95 % CI 1.49–7.01; p = 0.003), 25(OH)D level &lt; 30 ng/ml (OR 4.55; 95 % CI 1.86–11.16; p = 0.001), moderate PHA &lt; 1 hour per day (OR 2.67; 95 % CI 1.06–6.75; p = 0.037), walking &lt; 1 hour per day and &lt; 4 hours per week (OR 3.25; 95 % CI 1.26–8.38; p = 0.015 and OR 3.17; 95 % CI 1.19–8.46; p = 0.021, respectively). Conclusion. Reduced nutritional status was found in 51.9 % and average or low levels of PHA in 55.8 % of patients with OSP. The risk of OSP development was increased by low nutritional status, inadequate dietary calcium intake, low vitamin D levels, short duration of daily moderate exercise, and inadequate daily and weekly walking time.

Determinants of Bone Mass Accrual in Transgender and Gender Diverse Youth Undergoing Pubertal Suppression Therapy

Introduction/Background: Gender-affirming care for gender diverse and transgender (GDTG) youth includes puberty suppression with gonadotropin-releasing hormone agonists (GnRHa). Puberty is a critical period of bone mass accrual, and pubertal suppression may impact bone health. Previous studies have shown a decrease in areal bone mineral density (aBMD) Z-score while on puberty suppression. However, the rate of bone mass accrual and its determinants during GnRHa therapy are not known.Methodology: This is a retrospective chart review of GDTG youth with aBMD assessment within six months of starting GnRHa monotherapy at Cincinnati Children's Hospital Medical Center between 01/2011 and 12/2022. In individuals with follow-up aBMD assessment, we calculated their aBMD velocity and generated Z-scores using reference data from the Bone Mineral Density in Childhood Study. The determinants of baseline height-adjusted aBMD and aBMD velocity Z-scores were assessed with multiple linear regression models.Results: Thirty-six participants (36% assigned female at birth (AFAB), mean age at first aBMD assessment 12 ± 1.1 years) had baseline height-adjusted aBMD Z-score of -0.053 ± 0.79. Among 16 participants with follow-up aBMD assessment, the mean aBMD velocity Z-score was -0.42 ± 1.13 (-0.27 ± 0.79 in AFAB vs -0.52 ± 1.32 in assigned male at birth, p = 0.965). Baseline aBMD Z-scores significantly correlated with age at the first aBMD assessment (adjusted R2 0.124, p = 0.02) with combined modeling including age at first aBMD assessment and BMI Z-score being most significant (adjusted R2 0.21, p = 0.008). Only BMI Z-scores were positively associated with the aBMD-velocity Z-scores (adjusted R2 0.255, p = 0.046).Conclusions: GDTG youth undergoing GnRHa therapy appeared to have below-average aBMD velocity Z-scores. A lower BMI Z-score was a determinant of lower baseline height-adjusted aBMD and aBMD velocity Z-scores. Building on previous studies, our study highlights aBMD velocity as a novel technique for bone health surveillance in GDTG youth.

Bone Health In Patients With Inflammatory Bowel Disease (IBD)

Metabolic bone disease is prevalent in persons with immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD). Within these conditions the most common are osteoporosis and reduced bone mineral density (BMD), often termed osteopenia in adult patients, and refer to a decreased mineralization of the bone matrix. This decreased mineralization weakens the resistance of the bone to external forces, thus increasing the risk of fractures when external compressive or deforming forces are applied. Osteoporosis is asymptomatic in the absence of a fracture, and diagnosis generally occurs through the use of programmatic screening (most commonly dual energy x-ray absorption [DEXA]) or incidentally following the occurrence of a fracture. Osteoporosis is defined as a DEXA-measured BMD at the lumbar spine or proximal femur which falls more than 2.5 standard deviations below the mean value for healthy young adults (known as a T-score). BMD decreases of a lesser degree (a T-score falling between -1 and -2.5) are referred to as osteopenia. Osteoporosis is a major public health concern, owing to the significant morbidity and mortality that is attributed to fractures. While fractures may represent a time-limited hardship among persons in otherwise good health and function, major osteoporosis-related fractures, especially those of the femur and spine, can lead to permanent disability and premature mortality. In Canada, approximately 150 people per 100,000 suffer a hip fracture per year, which confers a 3-fold higher risk of mortality.

Contact states with femoral cortical bone and periprosthetic bone mineral density changes differ between traditional and newly introduced fully hydroxyapatite-coated stems.

The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group). The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded. There were significantly larger contact areas in Gruen zones 3, 5, and 6 in the N-HA group than in the T-HA group. At two years postoperatively, there was a significant decrease in BMD around the proximal-medial femur (zone 6) in the N-HA group and a significant increase in the T-HA group. BMD changes in both groups correlated with BMI or preoperative lumbar BMD rather than with the extent of contact with the femoral cortical bone. The N-HA-coated stem showed a significantly larger contact area, indicating a distal fixation pattern, compared with the traditional fully HA-coated stem. The T-HA-coated stem showed better preservation of periprosthetic BMD, two years postoperatively. Surgeons should consider these patterns of fixation and differences in BMD when selecting fully HA-coated stems for THA, to improve the long-term outcomes.

Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17β-estradiol (E2, 50 μg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of β-C-terminal telopeptide of type I collagen (β-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

Impact of Androgen Deprivation Therapy on Lumbar Spine Bone Health Using Quantitative Computed Tomography in a Propensity-Matched Cohort of Patients With Prostate Cancer

Purpose: Fragility fracture risk in patients with prostate cancer is an important issue. The purpose of this study was to accurately assess the impact of androgen deprivation therapy on lumbar spine bone loss using quantitative computed tomography in a propensity-matched cohort of patients with prostate cancer. Materials and Methods: Eighty-one patients with prostate cancer who underwent androgen deprivation therapy for 1 year were included. Thirty-nine of these patients were successfully propensity-matched with 39 of 68 patients from a control group who underwent robot-assisted radical prostatectomy without androgen deprivation therapy. Volumetric bone mineral density of trabecular bone in each vertebral body (L1-L4) was measured using quantitative computed tomography during staging and at 1 year after commencing treatment. The change in mean lumbar volumetric bone mineral density (L1-L4) was then calculated. Results: Propensity score matching successfully achieved comparable baseline patient characteristics and radiological parameters between the androgen deprivation therapy and control groups. In the androgen deprivation therapy group, the decrease in lumbar volumetric bone mineral density (L1-L4) was significantly greater with confirmed testosterone deficiency (−17.9 ± 12.0%) compared with the control group (−8.5 ± 10.8%, P &lt; .001). Conclusions: This study observed a 17.9% reduction in volumetric lumbar bone mineral density (g/cm3) after 1 year of androgen deprivation therapy, exceeding previously reported values (g/cm2) obtained using dual-energy X-ray absorptiometry. The potential overestimation of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry in older patients with prostate cancer because of concomitant lumbar degenerative disease is a possible reason for this discrepancy. Androgen deprivation therapy may decrease vertebral bone mass and increase the risk of vertebral fractures more than urologists realize.

The Na+/Ca2+ exchanger NCX3 mediates Ca2+ entry into matrix vesicles to facilitate initial steps of mineralization in osteoblasts.

Matrix vesicles (MVs) provide the initial site for amorphous hydroxyapatite (HA) formation within mineralizing osteoblasts. Although Na+/Ca2+ exchanger isoform-3 (NCX3, SLC8A3) was presumed to function as major Ca2+ transporter responsible for Ca2+ extrusion out of osteoblast into the calcifying bone matrix, its presence and functional role in MVs have not been investigated. In this study, we investigated the involvement of NCX3 in MV-mediated mineralization process and its impact on bone formation. Using differentiated MC3T3-E1 cells, we demonstrated that NCX3 knockout in these cells resulted in a significant reduction of Ca2+ deposition due to reduced Ca2+ entry within the MVs, leading to impaired mineralization. Consequently, the capacity of MVs to promote extracellular HA formation was diminished. Moreover, primary osteoblast isolated from NCX3 deficient mice (NCX3-/-) exhibits reduced mineralization efficacy without any effect on osteoclast activity. To validate this in vitro finding, μCT analysis revealed a substantial decrease in trabecular bone mineral density in both genders of NCX3-/- mice, thus supporting the critical role of NCX3 in facilitating Ca2+ uptake into the MVs to initiate osteoblast-mediated mineralization. NCX3 expression was also found to be the target of downregulation by inflammatory mediators in vitro and in vivo. This newfound understanding of NCX3's functional role in MVs opens new avenues for therapeutic interventions aimed at enhancing bone mineralization and treating mineralization-related disorders.

P306 Analysis risk factors for the decrease bone mineral density in cystic fibrosis

P306 Analysis risk factors for the decrease bone mineral density in cystic fibrosis

Evaluation of vitamin D deficiency and low bone mass in children with asthma in fars province: A case-control study.

Asthma is a chronic inflammatory pulmonary disease which affects 10%-20% of children and adolescents. Inhaled corticosteroids (ICS) is one of its most effective therapies. The effect of systemic corticosteroids on decreasing bone mineral density (BMD) was investigated and proved in children; however, the influence of ICSs on bone density has still remained unclear. This study evaluates the bone mineral density of children and adolescents with asthma in southern Iran and the associated factors, for example, amount of used inhaled steroid. This case-control study enrolled 41 children and adolescents (aged 8-18 years) with asthma and their age and gender-matched controls in 2019-2020. Serum Calcium, phosphate, vitamin D, and bone mineral density were measured. Their physical activity, sun exposure, and fracture history were evaluated subjectively. Lumbar BMD and BMD Z-score in patients showed no significant difference with controls (p = 0.23, p = 0.73). Also, it showed that there was no significant difference in biochemical studies, growth, and bone densitometry parameters between patients who used ICSs for less than 3 months/year corticosteroid therapy compared to those with equal or more than 3 months/year usage. Prevalence of vitamin D deficiency was 28% and 8% in the controls and patients, respectively (p = 0.005). The present study showed that 9.46% of children and adolescents with asthma had low bone mass for chronological age, and it is not significantly higher than normal population. Dosage of inhaled steroid did not associate with osteoporosis in these patients. Prevalence of vitamin D deficiency in patients was lower than normal population, probably due to receiving vitamin D in their routine follow-ups.

Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer.

The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors. The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT. After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2=0.319, P=0.037, and BMD was also positively correlated with pectoral muscle density, R2=0.329, P=0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism. Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.

Effect of long-term proton pump inhibitors on phosphocalcium metabolism and bone mineral density.

Aim: Although Proton pump inhibitors (PPIs) are well-tolerated, their long-term use may be associated with decreased bone mass. Methods: This is a case-control study including patients treated with PPIs (>1year) and control subjects who have not received PPIs treatment. Results: A total of 90 patients and 90 matched controls were included. PPIs use was associated with hypocalcemia and hypomagnesemia. Vitamin D3 deficiency and hyperparathyroidism were associated with PPIs use. Long-term PPIs use was significantly associated with decreased bone density. Risk factors of decreased bone mineral density (BMD) included age >50years, menopause, lack of sun exposure, double PPIs dose, daily intake, post-meal intake and association with a mucoprotective agent. Conclusion: Our results highlight the risk of decreased BMD in patients on long-term PPIs treatment.

Farnesyl Diphosphate Synthase Gene Associated with Loss of Bone Mass Density and Alendronate Treatment Failure in Patients with Primary Osteoporosis.

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; p = 0.026) and TH (CC = -2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.

Iron and bones: effects of iron overload, deficiency and anemia treatments on bone.

Iron is a vital trace element and exerts opposing effects on bone in both iron overload and iron deficiency situations. Remarkably, iron supplementation through intravenous infusion in patients with iron deficiency can also have detrimental effects on bone in special cases. The diverse mechanisms underlying these effects and their manifestations contribute to the complexity of this relationship. Iron overload impacts both bone resorption and formation, accelerating bone resorption while reducing bone formation. These effects primarily result from the direct action of reactive oxygen species (ROS), which influence the proliferation, differentiation, and activity of both osteoclasts and osteoblasts differently. This imbalance favors osteoclasts and inhibits the osteoblasts. Simultaneously, multiple pathways, including bone morphogenic proteins, RANK ligand, and others, contribute to these actions, leading to a reduction in bone mass and an increased susceptibility to fractures. In contrast, iron deficiency induces low bone turnover due to energy and co-factor deficiency, both of which require iron. Anemia increases the risk of fractures in both men and women. This effect occurs at various levels, reducing muscular performance and, on the bone-specific level, decreasing bone mineral density. Crucially, anemia increases the synthesis of the phosphaturic hormone iFGF23, which is subsequently inactivated by cleavage under physiological conditions. Thus, iFGF23 levels and phosphate excretion are not increased. However, in specific cases where anemia has to be managed with intravenous iron treatment, constituents-particularly maltoses-of the iron infusion suppress the cleavage of iFGF23. As a result, patients can experience severe phosphate wasting and, consequently, hypophosphatemic osteomalacia. This condition is often overlooked in clinical practice and is often caused by ferric carboxymaltose. Ending iron infusions or changing the agent, along with phosphate and vitamin D supplementation, can be effective in addressing this issue.