Search Results (85)

Improving phosphorus (P) utilization in broilers is crucial for reducing feed costs and environmental pollution. Bone mineralization trait is strongly associated with P utilization in poultry and is thus often used as an alternative trait for evaluating P utilization. Dentin matrix protein 1 (DMP1), an essential matrix protein for bone mineralization and P deposition, has been shown to be actively involved in P utilization in broilers, but the underlying mechanisms remain unclear. The current study aimed to investigate the possible mechanisms whereby DMP1 regulates P utilization of poultry by using gene silencing and overexpression technologies, combined with an in vitro model of primary broiler osteoblasts. The results showed that DMP1 overexpression augmented the P utilization of broiler osteoblasts, characterized by significant increases (p < 0.001) in P utilization rate, mineralization formation, alkaline phosphatase activity, and bone gla protein content. Meanwhile, DMP1 overexpression effectively (p < 0.05) activated the focal adhesion kinase (FAK) signaling, along with obvious (p < 0.01) decreases in fibroblast growth factor 23 (FGF23) expression and production. In contrast, DMP1 silencing reversed (p < 0.05) the above effects. Consistently, FAK activation promoted (p < 0.05) P utilization accompanied by remarkable (p < 0.05) decreases in FGF23 expression and production. Furthermore, gain- and loss-of-function assays demonstrated that a high level of FGF23 contributed to impaired P utilization, while a low level was beneficial. Interestingly, blocking FAK signaling not only recovered (p < 0.05) the FGF23 expression and production in DMP1 overexpressed cells but also obviously (p < 0.05) weakened their P utilization. These findings indicate that DMP1 inhibits FGF23 expression by activating FAK, thereby contributing to P utilization in broiler osteoblasts. They reveal a novel DMP1-FAK-FGF23 regulatory axis in broiler osteoblasts and provide a potential target for improving P efficiency in poultry. Full article

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) is associated with vascular calcification and diabetes-related complications. However, the effect of exosomal MALAT1 derived from macrophages induced by hyperglycemia on vascular calcification (VC) remains unclear. In this study, we investigated the effect of VC and its regulatory mechanisms in cultured vascular smooth muscle cells (VSMCs) and diabetic rats by exosomal MALAT1 derived from macrophages treated with high levels of glucose. Macrophages and VSMCs were cultured in 25 mM glucose. Macrophages exposed to high glucose exhibited increased expression of exosomal MALAT1. When transferred to VSMCs, exosomal MALAT1 significantly suppressed the expression of miR-143-3p while upregulating Matrix Gla protein (MGP, an inhibitor of VC) mRNA and protein levels. Interventions using MALAT1 siRNA or miR-143-3p mimics effectively reversed this effect. Both MALAT1 siRNA and overexpression of miR-143-3p significantly increased the calcium content in cultured VSMCs and in the carotid artery of diabetic rats following balloon injury. Balloon injury to the carotid artery in diabetic rats treated with macrophage-derived exosomes significantly increased the expression of MALAT1 and MGP while reducing the expression of miR-143-3p in the carotid artery. These findings demonstrate that macrophage-derived exosomal MALAT1 modulates VC via the MALAT1/miR-143-3p/MGP axis under hyperglycemic conditions. The results suggest that targeting exosomal MALAT1 may offer a novel and effective therapeutic approach for mitigating VC in metabolic disorders such as diabetes. Full article

Background and Objectives: Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those on hemodialysis. Once considered a passive process, VC is now recognized as an active, cell-mediated pathology influenced by mineral dysregulation, chronic inflammation, and oxidative stress. This review aims to synthesize current evidence on the underlying mechanisms of VC in CKD and hemodialysis, with particular focus on emerging biomarkers and therapeutic implications. Materials and Methods: A structured narrative review was conducted by searching PubMed, Web of Science, ScienceDirect, and Google Scholar. The final search was completed on 29 August 2025. A total of 1326 articles were initially retrieved, of which 65 met the inclusion criteria and were analyzed. Studies addressing VC mechanisms, the bone–vascular axis, mineral metabolism, vitamin K–dependent proteins, and biomarkers such as matrix Gla protein (MGP), osteocalcin (OC), and intact parathyroid hormone (iPTH) were included. Results: VC in CKD arises from phenotypic transformation of vascular smooth muscle cells, vesicle-mediated calcification, oxidative stress, and impaired activity of endogenous calcification inhibitors. Disruption of the fibroblast growth factor 23 (FGF23)–Klotho axis and secondary hyperparathyroidism further exacerbate vascular pathology. Among emerging biomarkers, dp-ucMGP reflects vitamin K deficiency and correlates with calcification burden, while OC and iPTH provide insight into bone–vascular crosstalk and mineral turnover. However, biomarker interpretation is limited by assay variability, renal clearance, and clinical heterogeneity. Conclusions: VC in CKD represents a complex process driven by systemic and cellular dysregulation. While biomarkers such as dp-ucMGP, OC, and iPTH offer mechanistic insights and prognostic potential, further validation is required for clinical application. A multimarker approach, combined with individualized management of mineral metabolism, may improve risk stratification and therapeutic targeting in this high-risk population. Full article

Background/Objectives: Arterial stiffness increases with progressive worsening of renal function and predicts cardiovascular mortality in patients with chronic kidney disease. The effects of vitamin K-dependent proteins in vascular health and the implications of vitamin K epoxide reductase gene (VKORC1) polymorphisms in calcification and warfarin sensitivity are well known, but their roles in arterial stiffness are not known. We investigated the influence of common polymorphisms in this gene (−1639G>A, +1173C>T, +1542G>C, +2255C>T, and +3730G>A) on stiffness and calcification markers in 302 CKD patients. Methods: Blood pressure, aortic pulse wave velocity (aPWV), coronary artery calcification (CAC), and aortic calcification (AC) were assessed together with the total uncarboxylated matrix Gla protein (t-uncMGP). Results: Genotyping subjects for +1542G>C and +3730G>A showed higher genotype-specific aPWV and lower t-uncMGP (p < 0.05). The combined recessive allele model showed a significant stepwise reduction in aPWV (p < 0.005); subjects homozygous for both risk alleles had the highest aPWV compared to those carrying one or none. In a multiple regression model adjusting for age, gender, mean pressure, BMI, and racial group, each +1542G allele and +3730A allele were independently associated with a 0.8 m/s (95% CI 0.09 to 1.57) and 1.0 m/s (95% CI 0.14 to 1.98) elevation of aPWV, respectively. Although serum t-uncMGP levels correlated inversely with CAC score (p < 0.001), VKORC1 genotypes did not. Conclusions: We demonstrated for the first time that VKORC1 polymorphisms (+1542G>C and +3730G>A) influence arterial stiffness and serum t-uncMGP levels in CKD patients. These findings suggest that vitamin K-dependent processes may be important in arterial stiffness, possibly by modulating calcification of the vessel wall. Full article

Cardio-kidney-metabolic (CKM) syndrome represents an integrated clinical and molecular continuum encompassing metabolic dysfunction, cardiovascular disease and chronic kidney disease. This multidimensional disorder arises from interdependent biological pathways that extend beyond conventional risk factors. Emerging evidence highlights a group of adipokines and vascular modulators—including retinol-binding protein 4 (RBP4), lipocalin 2 (LCN2), apolipoprotein M (ApoM), Klotho and matrix Gla protein (MGP)—emerging molecular modulators with potential involvement in CKM pathophysiology. Pro-inflammatory adipokines such as RBP4 and LCN2 contribute to insulin resistance, oxidative stress and endothelial dysfunction. In contrast, protective molecules including ApoM and Klotho preserve nitric oxide bioavailability, lipid metabolism and antioxidant defense. MGP modulates vascular calcification and adipose remodeling, with its inactive form (dp-ucMGP) linked to vascular stiffness and renal decline. The combined dysregulation of these molecules sustains cycles of inflammation, oxidative stress and tissue remodeling that drive CKM progression. Collectively, current data support their dual role as biomarkers and therapeutic targets. Nonetheless, clinical translation remains limited, emphasizing the need for standardized assays, longitudinal validation, and integrative multimarker approaches within precision medicine frameworks for CKM syndrome. Full article

Male sex and aging are risk factors for fibro-calcific aortic valve disease (FCAVD), indicating an understudied influence of sex hormones. Valvular interstitial cells (VICs) from female and male donors were isolated and exposed to pro-calcifying medium (PM), and the expression of matrix gla protein (MGP), fibronectin (FN1) and bone morphogenic protein 2 (BMP2) was analyzed. The effect of sex hormones on hydroxyapatite (HA) deposition by VICs was also analyzed. Exposure to PM increased MGP gene expression in male (n = 5, +5.8-fold, p = 0.031), and female VICs (n = 6, +4.9-fold, p = 0.004). In female VICs a +3.5-fold MGP increase accompanied the transition from the fibrotic to the calcific phase (p = 0.022 vs. males) while in male VICs the increase was delayed to the calcific phase. Female VICs upregulated FN1 (+1.8-fold, p = 0.003), while male VICs upregulated BMP2 (+3.7-fold, p = 0.05). 5α-dihydrotestosterone increased HA deposition +6.3-fold in male and +5.2-fold in female VICs (p ≤ 0.001 and p < 0.04, respectively). It further decreased BMP2 (p < 0.001) in male VICs and increased MGP in female VICs (p = 0.087). Female VICs decreased HA deposition when exposed to progesterone (−2.4-fold, p = 0.037 vs. PM) and estrogen (−2.0-fold, p = 0.072). In summary, VICs show donor-sex-specific gene expression which is modifiable by 5α-dihydrotestosterone. This needs to be considered when designing in vitro regulatory studies. Full article

Background: Vitamin K is a cofactor necessary for the biological activity of proteins like Matrix Gla Protein (MGP), which reduce calcification and help preserve lung function. This study aims to determine, first, whether low vitamin K status is associated with chronic obstructive pulmonary disease (COPD), and secondary, whether the level of vitamin K is associated with COPD severity, smoking exposure, or mortality. Methods: The plasma concentration of dephosphorylated uncarboxylated (dp-uc) MGP was used as an inverse biomarker for vitamin K in 98 COPD patients from the CODEX-P COPD study and 986 controls from the DanFunD study. Low vitamin K status was defined as the upper quartile of dp-ucMGP (>589 pmol/L). Using a logistic regression model, we examined whether low vs. high/moderate vitamin K status increased the odds ratio (OR) of having COPD. Secondary analyses, in the COPD cohort only, examined the association between low vitamin K status and COPD severity, smoking exposure in packyears and all-cause mortality, using a Welch’s t-test and log-rank test, respectively. Results: Low vitamin K status was associated with increased odds of having COPD, OR 9.7 (95% CI [5.5 to 17.5], p < 0.001). We found no associations between low vitamin K and COPD severity (est. −0.03, p = 0.7; 95% CI [−0.2 to 0.1]), smoking exposure (p = 0.7), or all-cause mortality (p = 0.5). Conclusions: Low vitamin K status was associated with substantially higher odds of having COPD compared to high/moderate vitamin K status. No association was found between low vitamin K status and COPD severity, smoking exposure, or all-cause mortality. Further studies are needed to determine if vitamin K plays a role in the pathophysiology of COPD and whether supplement therapy is indicated. Full article

Background/Objectives: Post-menopausal women are at an increased risk of developing cardiovascular disease. Menaquinone-7 (MK-7) is a fat-soluble vitamin involved in coagulation and maintaining vascular health. The aim of the post hoc analysis of this one-year study is to investigate the effects of MK-7 supplementation on the vascular parameters in pre-, peri-, and post-menopausal women. Methods: In a clinical intervention trial (NCT02404519), a total of 165 women with a low vitamin K status received either 180 µg of MK-7 daily (n = 82) or a matching placebo (n = 83) for one year. Established vascular parameters were measured before and after one year of vitamin K2 supplementation. Pre-, peri-, and post-menopausal women were subdivided according to arterial stiffness, with a high b-stiffness index defined as being greater than the overall median of 9.83. Results: The post hoc analyses showed a significant decrease in desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) plasma levels after MK-7 supplementation (pre/peri, p = 0.009; post, p < 0.001). MK-7 treatment significantly attenuated vascular stiffness in post-menopausal women (placebo +49.1% ± 77.4; MK-7 +9.4% ± 67.1; p = 0.035). Post-menopausal women with a high stiffness index showed significantly improved vascular markers after MK-7 treatment, e.g., a decreased blood pressure at brachialis (−3.0% ± 9.0; p = 0.007) and an increased distensibility coefficient (+13.3% ± 32.3; p = 0.040). Conclusions: Our results confirm that menopause affects vascular health status. Post-menopausal women with an increased stiffness benefit most from MK-7 supplementation, with a significantly improved blood pressure. Further research is needed to unravel the beneficial effects of MK-7 in post-menopausal women. Full article

Background/Objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients. Methods: This case–control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). CAD risk factors were evaluated and related to serum levels of vitamin K2 analogs. The CAD group was further subdivided into stable angina, STEMI, NSTEMI, and unstable angina groups to investigate potential differences in vitamin K2 analog levels. Results: Patients experiencing acute coronary syndrome exhibited notably reduced serum levels of MK-4 and MK-7 (1.61 ± 0.66, and 1.64 ± 0.59 ng/mL, respectively) in comparison to the control group (2.29 ± 0.54, and 2.16 ± 0.46 ng/mL, respectively), with MK-4 and MK-7 displaying stronger associations with CAD risk indicators. Notable variations in vitamin K2 analog levels were found between CAD patients and control groups (p < 0.001). Unstable angina patients showed the lowest serum levels of MK-4 and MK-7. Conclusions: The present study demonstrated a higher prevalence rate of vitamin K2 deficiency among patients with CAD. The most pronounced decrease in MK-4 and MK-7 was observed in unstable angina patients. Moreover, these outcomes indicate the imperative requirement for an integrative approach that incorporates metabolic, lipid, and vitamin K2-related pathways in the risk stratification and management of CAD. Full article

Background/Objectives: Vitamin K deficiency in chronic kidney disease (CKD) could potentially occur due to multiple factors, leading to an increased risk of vascular and valvular calcifications. Vitamin K status can be indirectly assessed by measuring the blood levels of vitamin K-dependent proteins (VKDPs), such as matrix GLA protein (MGP). This study aims to examine the relationship between the levels of inactive MGP (dp-uc MGP) and the presence of valvular calcifications, as well as its association with mortality in hemodialysis patients. Methods: We conducted a single-center study that included 45 CKD G5D patients (hemodialysis for 6 months to 10 years) followed up for 24 months. All patients have been assessed at baseline regarding cardiovascular disease (medical history, echocardiography). Moreover, using standard methods, we determined blood biochemistry, complete blood count, and matrix GLA protein. At 24 months of follow-up, we assessed all-cause mortality and cardiovascular mortality. Results: In the studied hemodialysis patients, mean dp-uc MGP was 3285.93 +/− 2092.85 pmol/L. Patients with valvular calcifications had higher levels of dp-uc MGP compared to those without (4521.08 +/− 2263.82 vs. 2487.53 +/− 1446.94 pmol/L, however not statistically significant). The presence and severity of valvular calcifications were significantly associated with the history of treatment with vitamin K antagonists (p < 0.05). After 24 months of follow-up, we found an all-cause mortality rate of 24.4%. The level of dp-uc MGP was higher in the group of patients that died (3884.81 +/− 2439.20 vs. 3133.09 +/− 1925.26 pmol/L, p > 0.05). Patients with more than one valvular calcification on echocardiography had a significantly higher all-cause mortality risk (p = 0.04). In terms of traditional risk factors, we observed an increased risk of all-cause mortality in patients with a history of diabetes mellitus (p = 0.02) and aortic stenosis (p = 0.01). However, other cardiovascular markers, such as coronary heart disease and ejection fraction < 50%, did not have a statistically significant impact on mortality in our patients. Conclusions: In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP, especially dp-uc MGP, is a predictor of valvular calcifications. Severe valvular calcifications, aortic stenosis, and the presence of diabetes mellitus are risk factors for all-cause mortality in hemodialysis patients. Full article

Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease. However, VC may occur earlier and faster in these patients if it is associated with new or non-traditional risk factors such as oxidative stress, anemia, and inflammation. In chronic kidney disease, several pathophysiological processes contribute to vascular calcifications, including osteochondrogenic differentiation of vascular cells, hyperphosphatemia and hypercalcemia, and the loss of specific vascular calcification inhibitors including pyrophosphate, fetuin-A, osteoprotegerin, and matrix GLA protein. In this review we discuss the main traditional and non-traditional risk factors that can promote VC in patients with kidney disease. In addition, we provide an overview of the main pathogenetic mechanisms responsible for VC that may be crucial to identify new prevention strategies and possible new therapeutic approaches to reduce cardiovascular risk in patients with kidney disease. Full article

Matrix Gla protein (MGP) is a vitamin K-dependent γ-carboxylated protein that was initially identified as a physiological inhibitor of ectopic calcification, primarily affecting cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for the Keutel syndrome, a condition characterized by abnormal calcifications in the cartilage, lungs, brain, and vascular system. MGP has been shown to be dysregulated in several tumors, including cervical, ovarian, urogenital, and breast cancers. Using bioinformatic approaches, transcription factor binding sites (TFBSs) containing CpG dinucleotides were identified in the MGP promoter, including those for YY1, GATA1, and C/EBPα. We carried out functional tests using transient transfections with a luciferase reporter assay, primarily for the transcription factors YY1, GATA1, C/EBPα, and RUNX2. By co-transfection analysis, we found that YY1, GATA1, and C/EBPα repressed the MGP promoter. Furthermore, the co-transfection with RUNX2 activated the MGP promoter. In addition, MGP expression is negatively or positively correlated with the studied TFs’ expression levels in several cancer types. This study provides novel insights into MGP regulation by demonstrating that YY1, GATA1, and C/EBPα are negative regulators of the MGP promoter, and DNA methylation may influence their activity. The dysregulation of these mechanisms in cancer should be further elucidated. Full article

Vascular calcification (VC) is a complex process involving vascular smooth muscle cell (VSMC) osteogenic differentiation, inflammation, and extracellular vesicle (EV) calcification and communication networks. Gla rich protein (GRP) is a calcification inhibitor involved in most of these processes. However, the molecular mechanism of GRP in VC and the specific characteristics, cargo, and functionality of calcifying EVs require further elucidation. Here, we use a combination of human ex vivo aortic fragments and primary vascular smooth muscle cell (VSMC) models to obtain new information on GRP function in VC and EVs released by VSMCs. We demonstrate that GRP inhibits VSMC osteogenic differentiation through downregulation of bone-related proteins and upregulation of mineralization inhibitors, with decreased mineral crystallinity in EVs deposited into the tissue extracellular matrix (ECM). EVs isolated by ultracentrifugation at 30K and 100K from the cell media (CM) and deposited in the ECM from control (CTR) and mineralizing (MM) VSMCs were biochemically, physically, and proteomically characterized. Four different EV populations were identified with shared markers commonly present in all EVs but with unique protein cargo and specific molecular profiles. Comparative proteomics identified several regulated proteins specifically loaded into MM EV populations associated with multiple processes involved in VC. Functional analysis demonstrated that 30K and 100K ECM-MM EVs with higher calcium and lower GRP levels induced macrophage inflammation. Our findings reinforce the functional relevance of GRP in multiple VC processes and suggest that ECM EVs released under calcification stress function as a new signaling axis on the calcification–inflammation cycle. Full article

Objectives: Identifying reliable biomarkers to predict mortality in critically ill patients is crucial for optimizing management in intensive care units (ICUs). Inflammatory and metabolic markers are increasingly recognized for their prognostic value. This study aims to evaluate the association of various inflammatory and metabolic markers with ICU mortality. Methods: This prospective observational study was conducted from January 2023 to January 2024 in the City Hospital’s ICU. A total of 160 critically ill patients were enrolled. Laboratory parameters, including white blood cell (WBC) count, red cell distribution width (RDW), platelet count, neutrophil count, mean platelet volume (MPV), monocyte count, lymphocyte count, procalcitonin (PCT), C-reactive protein (CRP), calcium (Ca⁺⁺), and vitamin D levels, were analyzed. Additionally, ratios such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory index (SII), and pan-immune-inflammation value (PIV) were calculated. Plasma levels of Gla-rich protein (GRP) and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) were measured using ELISA. Results: The mean age of the patients included in the study was 60.5 ± 15.8 years. Cardiovascular disease was present in 72 patients (45%), respiratory system disease in 58 (36%), and chronic kidney disease (CKD) in 38 (24%). Additionally, 61 patients (38%) had diabetes, and 68 (42%) had hypertension. Inflammatory markers, including PLR, NLR, and PIV, were all significantly higher in non-survivors, while calcium and vitamin D levels were lower (p < 0.05). Higher WBC, RDW, neutrophil count, PLR, NLR, PIV, CRP, procalcitonin, GRP, and dp-ucMGP levels were positively correlated with longer hospital stays and increased mortality. In contrast, platelet and lymphocyte counts were negatively correlated with both outcomes (p < 0.05). Vitamin D levels showed an inverse relationship with both hospital stay and mortality, indicating that lower levels were associated with worse outcomes (p < 0.05). In multiple logistic regression analysis, elevated WBC count (OR = 1.20, p = 0.02), RDW (OR = 1.35, p = 0.01), neutrophil count (OR = 1.25, p = 0.01), MPV (OR = 1.20, p = 0.02), PLR (OR = 1.30, p = 0.01), NLR (OR = 1.40, p = 0.001), PIV (OR = 1.50, p = 0.001), CRP (OR = 1.32, p = 0.01), procalcitonin (OR = 1.45, p = 0.001), GRP (OR = 1.40, p = 0.001), and dp-ucMGP (OR = 1.30, p = 0.001) levels were significantly associated with increased mortality. Conclusions: Inflammatory and metabolic markers, particularly NLR, PLR, PIV, GRP, and dp-ucMGP, are strong predictors of mortality in ICU patients. These markers provide valuable insights for risk stratification and early identification of high-risk patients, potentially guiding more targeted interventions to improve outcomes. Full article

Background/Objectives: Chronic kidney disease and mineral bone disorders (CKD-MBD) are frequently associated with an increased risk of both vascular calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and bone Gla protein (BGP), have pivotal roles both for VCs and BFs. The VIKI study highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs beyond the beneficial effect of reducing PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age- and sex-matched patients treated with calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on an individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusions: This study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Full article