Maintaining Bone Health Research Articles

The Critical Role of Trace Elements in Bone Health

Trace elements are essential for human physiology and crucial in maintaining bone health and regulating bone metabolism [...]

Effect of walking and bone joint exercise on enhancing bone remodeling in menopausal women: A randomized controlled trial

Osteoporosis increases fracture risk and reduces quality of life in menopausal women. Although physical activity, such as walking and bone joint exercise, is known to help maintain bone health, its effectiveness needs further examination. The aim of this study was to analyze the effects of physical activity, in particular walking and bone joint exercise, on enhancing bone remodeling in menopausal women. A randomized controlled trial was conducted among menopausal women and allocated into three groups: walking, bone joint exercise, and control groups. The intervention was provided for eight weeks, with the outcomes measured before and after the intervention. The study assessed five bone remodeling biomarkers: estrogen, parathyroid hormone (PTH), receptor activator of nuclear factor kappa-β ligand (RANKL), tumor necrosis factor-alpha (TNF-α), and bone mineral density (BMD). The paired sample student t-test and ANOVA were used to assess the effects of the interventions. The results indicated that, compared to pre-intervention, both walking and bone joint exercise significantly increased the estrogen (p=0.026 and p=0.023, respectively), decreased RANKL (p=0.019 and p=0.002, respectively), decreased PTH levels (p=0.022 and p=0.048, respectively) and increased the BMD scores (p=0.001 and p<0.001, respectively). In the control group, none of the remodeling biomarkers significantly changed except the mean level of TNF-α, which was increased significantly (p=0.001). This study highlights that structured exercise, such as walking and bone joint exercise, can significantly enhance bone remodeling markers in menopausal women. Therefore, implementing such physical activities into management may provide benefits to menopausal women.

The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations – A narrative review

This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms.

Shared Genetic Architecture and Causal Relationship between Serum 25-Hydroxyvitamin D and Bone Mineral Density.

Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD). Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417,580) and estimated heel BMD (eBMD, N = 426,824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design. Despite a lack of global genetic correlation (rg = -0.001, P = 0.95), a significant local signal was discovered at 5p11-5q11.9. Two-sample Mendelian randomization (MR) indicated no causal association in the overall population (β = 0.003, 95% CI = -0.04∼0.03, P = 0.93), while positive causal effects were observed in males (β = 0.005, 95% CI = 0.00∼0.01, P = 0.03) and the elderly (β = 0.009, 95% CI = 0.00∼0.02, P = 0.01) according to one-sample MR. A total of 49 pleiotropic SNPs, with 4 novel SNPs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exo-/endocrine and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes. This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among males and the elderly. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.

7590 Bone Mineral Content In Women With Functional Hypothalamic Amenorrhea Compared To Eumenorrheic Controls And Recently Menopausal Women

Abstract Disclosure: N. Safwan: None. E.R. Uddenberg: None. M.D. Hurtado: None. M. Saadedine: None. S.S. Faubion: None. O. Obrutu: None. S.L. Berga: None. M.D. Pisarska: None. C. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea due to suppression of GnRH associated hypercortisolemia resulting in chronic hypoestrogenemia. FHA occurs as a result of varying combinations of psychosocial stress, excessive exercise, and/or disordered eating. FHA is associated with decreased bone mineralization; however, it is unknown how bone health compares to older, menopausal women who also experience bone loss. We compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women and evaluated if previous oral contraceptive (OC) use among FHA women has an impact on bone mineral density (BMD). Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. All participants were not on hormone therapy. FHA was defined as amenorrhea >3 consecutive months, estradiol <50 pg/ml, FSH <10 mIU/L, and LH <10 mIU/L, excluding other etiologies including PCOS, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menses confirmed with day 22-24 progesterone >3 ng/ml. Recently menopausal women had natural menopause <3 years of final menstrual period, and FSH >30 mIU/L. DXA bone health parameters were measured using Lunar iDXA (GE) including BMD from the lumbar spine (L1-L4) and hip. Statistical analysis included nonparametric testing with pairwise Wilcoxon rank sum and Kruskal Wallis, reported as median [interquartile ranges]. Results: By design, the mean age of FHA was 28 ± 6 yr, 29 ± 3 yr for controls, and 54 ± 2 yr for recently menopausal women (p<0.0001). There were no differences in weight or BMI among the groups (p=0.27, p=0.30, respectively). BMD L1-L4 differed among the three groups with 1.10 g/cm2 [1.00, 1.24] for FHA, 1.18 [1.15, 1.29] for eumenorrheic controls, and 1.02 [0.96, 1.08] for menopausal women (p=0.002). Pairwise analysis revealed a significant difference in BMD L1-L4 between FHA and controls (p=0.04) and menopausal women and controls (p=0.009, age-adjusted). However, there was no difference in BMD L1-L4 between FHA and menopausal women (p=0.08, age-adjusted). In FHA women with previous OC use, BMD L1-L4 was not different from eumenorrheic controls (p=0.20), while BMD L1-L4 differed from that of recently menopausal women (p=0.004). These differences were not observed at the hip. Conclusion: Compared to eumenorrheic controls, lumbar spine BMD in young women with FHA (mean age 28 yr) was similar to recently menopausal women (mean age 54 yr) emphasizing the profound bone impact of FHA. Previous OC use seems to mitigate FHA bone mineralization changes. Future studies should investigate if bone health differs among women with FHA based on underlying cause and if previous OC use plays a role in maintaining bone health. Presentation: 6/3/2024

Resveratrol enhances the protective effects of calcium supplements on spinal cord injury-induced osteoporosis by targeting the SIRT1/FOXO3a pathway.

Spinal cord injury (SCI) often leads to osteoporosis due to factors like immobilization and hormonal imbalances. Calcium supplements are prescribed to help maintain bone health, but their efficacy may be limited. This study investigated whether resveratrol (RSV), a polyphenolic compound, could enhance the protective effects of calcium supplements on SCI-induced osteoporosis via the SIRT1/FOXO3a pathway, which regulates bone metabolism. Surgical cord transection induced SCI at the T9 vertebral level. An SCI mouse model was used with four groups: sham, SCI, SCI + 2% calcium, and SCI + calcium + RSV (20mg/kg body weight). ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌Biomechanical testing, gene expression, and Western blots were performed. Resveratrol and calcium supplementation synergistically preserved bone mass, microarchitecture, strength, and fracture resistance compared to calcium alone after SCI. This was accompanied by upregulated osteoblast markers, downregulated osteoclast markers, and increased SIRT1/FOXO3a expression and activation. The results suggest resveratrol enhances calcium's bone-protective effects in SCI-induced osteoporosis by modulating the SIRT1/FOXO3a pathway and osteoblast/osteoclast activities. Combining resveratrol with calcium supplementation may be a promising therapeutic approach for managing SCI-induced osteoporosis.

Effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women: a meta-analysis

BackgroundThe bone status of postmenopausal women is worsening. In fact, postmenopausal period is the high incidence stage of osteoporosis and falls. Notably, a recent study has pointed out that exercise can improve bone health in postmenopausal women. However, the effect of Tai Chi exercise on postmenopausal women is controversial. Therefore, a meta-analysis was designed to analyze the effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women.MethodsThe researches on Tai Chi improving the bone health of postmenopausal women before August 31, 2023 were collected from Chinese and English databases, such as PubMed, Embase, and Web of Science, etc. The risk of bias of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials. Besides, R software 4.3.1 was employed to analyze the effect sizes in the meta-analysis to summarize the impact of Tai Chi on vertebral bone mineral density, serum calcium, clinical balance scores, the number of falls, total falls, and health status scores in postmenopausal women.ResultsThere were 12 studies eventually included in this meta-analysis. A total of 1,272 postmenopausal women were involved, including 628 in the experimental group (intervention with Tai Chi exercise) and 644 in the control group (without any intervention). Briefly, postmenopausal women practicing Tai Chi presented a significant increase in vertebral bone density [standardized mean difference (SMD) = 0.37, 95% confidence interval (CI) (0.04–0.71), P = 0.03] and health status score [SMD = 0.25, 95% CI (0.01–0.49), P = 0.04]. In contrast, there were no significant differences for postmenopausal women between the two groups in terms of serum calcium [SMD = -0.01, 95% CI (-0.39, 0.36), P = 0.77], clinical balance [SMD = 0.17, 95% CI (-0.01, 0.46), P = 0.23], number of falls [SMD = -0.61, 95% CI (-1.24, 0.02), P = 0.06] and total falls [odds ratio = 0.35, 95% CI (0.11–1.12), P = 0.07].ConclusionTai Chi exercise can improve the bone mineral density of postmenopausal women, thereby maintaining bone health. Hence, Tai Chi exercise is necessary to prevent osteoporosis.

The Manganese-Bone Connection: Investigating the Role of Manganese in Bone Health.

The complex relationship between trace elements and skeletal health has received increasing attention in the scientific community. Among these minerals, manganese (Mn) has emerged as a key element affecting bone metabolism and integrity. This review examines the multifaceted role of Mn in bone health, including its effects on bone regeneration, mineralization, and overall skeletal strength. This review article is based on a synthesis of experimental models, epidemiologic studies, and clinical trials of the mechanisms of the effect of Mn on bone metabolism. Current research data show that Mn is actively involved in the processes of bone remodeling by modulating the activity of osteoblasts and osteoclasts, as well as the main cells that regulate bone formation and resorption. Mn ions have a profound effect on bone mineralization and density by intricately regulating signaling pathways and enzymatic reactions in these cells. Additionally, Mn superoxide dismutase (MnSOD), located in bone mitochondria, plays a crucial role in osteoclast differentiation and function, protecting osteoclasts from oxidative damage. Understanding the nuances of Mn's interaction with bone is essential for optimizing bone strategies, potentially preventing and managing skeletal diseases. Key findings include the stimulation of osteoblast proliferation and differentiation, the inhibition of osteoclastogenesis, and the preservation of bone mass through the RANK/RANKL/OPG pathway. These results underscore the importance of Mn in maintaining bone health and highlight the need for further research into its therapeutic potential.

Comparative Evaluation of Effectiveness of Omega-3 Fatty Acids as an Adjunct to SRP with Conventional SRP: A Randomized Clinical Trial.

This study aims to compare the effectiveness of "omega-3 fatty acids" as an auxiliary to "scaling and root planing (SRP)" with traditional "scaling and root planing" in periodontal treatment in humans. This study is a randomized control trial and was carried out over a period of 3 months (registered on 02/07/2023). Thirty patients were singled out according to the inclusion criteria, each having periodontitis (Stage II Grade B), and were arbitrarily distributed into two groups (control and test). The test group was treated with "scaling and root planing" along with the adjunctive application of "omega-3 fatty acids" while the control group was treated with "scaling and root planing" alone. Monthly follow-up was carried out over 90 days. Clinical parameters such as pocket probing depth (PPD), gingival index (GI), bleeding index (BI), and plaque index (PI) were measured respectively at baseline and 3 months. The data was recorded and statistically analyzed. The soft tissue architecture remained stable. The mean full mouth plaque index (FMPI) score was statistically significant (p < 0.001) when the control group was compared to the test group with a mean difference of 0.12 ± 0.02. The mean full mouth papillary bleeding index (FMPBI) score decreased at 3 months and was statistically significant compared to baseline with a mean difference of 0.24 ± 0.04 (p < 0.001). When the test group was compared with the control group, the FMGI was not significant (p = 0.02), with a mean difference of 0.16 ± 0.19. The PPD was not significant (p =1) when comparing both the groups, with a mean difference of 0 ± 0.66. Although the clinical parameters were statistically significant at 3 months when compared to baseline in both the groups, the FMGI and PPD were not significant. The combined action of using omega-3 fatty acid as an auxiliary to conventional scaling and root planing improved the periodontal parameters including both the soft and hard tissue outcomes. The present study indicated that supplementary usage of omega-3 fatty acids is more beneficial for treating chronic and mild periodontitis than scaling and root planing alone. Omega-3 fatty acids can be used as energy for our cells, reduce the risk of blood clotting, maintain bone health, regulate metabolism, and reduce inflammation. Host modulatory therapy (HMT) with omega-3 fatty acids aims at reducing inflammation. With HMT as an adjunct, a better result of periodontal therapy was expected. It enhanced the positive effects on periodontal parameters and both the soft and hard tissue outcomes. How to cite this article: Salian S, Dhadse PV, Patil R, et al. Comparative Evaluation of Effectiveness of Omega-3 Fatty Acids as an Adjunct to SRP with Conventional SRP: A Randomized Clinical Trial. J Contemp Dent Pract 2024;25(5):440-444.

Effects of the dietary supplementation of manganese on growth, skeletal development, oxidative stress and bone metabolism related genes in gilthead seabream (Sparus aurata) larvae

Manganese (Mn) is an essential element necessary for normal growth, antioxidant defense and maintaining bone health. Knowledge about the effects of dietary Mn levels in gilthead seabream (Sparus aurata) larvae performance is still scarce. To determine the effects of dietary Mn levels on growth, survival, skeletal development and expression of antioxidant and bone metabolism related genes, gilthead seabream larvae were fed six experimental microdiets supplemented with manganese sulfate monohydrate (MnSO4.H2O) (contained 6.3, 39, 75, 79, 200 and 270 mg Mn/kg diet). After 26 days of feeding, dietary Mn levels had no effect on larval survival. However, larvae fed the non-supplemented diet (6.3 mg Mn/kg) showed signs of Mn deficiency, including growth reduction, low whole body Mn content, lower expression of mnsod, runx2, oc, and reduced bone mineralization. The poor vertebral body mineralization and low bone relative gene expression in seabream larvae was related to a marked increase in the number of fish with total skeletal anomalies and anomalies of the caudal vertebrae region. On the contrary, larvae fed with Mn supplemented diet up to 270 mg Mn/kg showed increased growth and whole body Mn content, up-regulated mnsod, runx2, alp, opn and oc expression, as well as increased bone mineralization, and reduced number of fish with skeletal anomalies. Therefore, the findings suggest that adequate dietary Mn supplementation positively influences the growth, skeletal development, and antioxidant defense of gilthead seabream larvae, preventing the manifestation of Mn deficiency-related issues.

THE ROLE OF VITAMIN D IN IMMUNE MODULATION: A REVIEW OF CLINICAL IMPLICATIONS

Vitamin D, often celebrated for its crucial role in maintaining bone health, has garnered significant attention in recent years for its multifaceted contributions to immune modulation. The study aims to find Vitamin D's role in immune modulation. The innate immune system is the first line of defense against invading pathogens, and its leading roles are rapid responses, identification of the pathogen, and neutralization to avoid the aggravation of the disease. The role of Vitamin D in immune modulation extends across a spectrum of immune-related disorders, underscoring its significance in maintaining immune homeostasis and preventing disease. The immune modularity of vitamin D is mainly through the active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]; this hormone binds to the Vitamin D receptor (VDR) inherent in several immune cells. This binding triggers the process of gene expression alterations that impact the abilities and duplication of these cells. For instance, in multiple sclerosis (MS), Vitamin D inhibits the production of Th1 and Th17, which are pro-inflammatory T-cells, while enhancing Tregs, which results in the curbing of inflammation and autoimmunity. Vitamin D is pivotal in immune modulation, influencing innate and adaptive immune responses. Its deficiency is linked to an increased risk and severity of various immune-related disorders, highlighting the importance of maintaining adequate Vitamin D levels.

Nutrition to support a healthy skeleton

Background. Bone tissue is actively exposed to environmental factors and lifestyle. Since the bone mass accumulated in childhood will determine the state of the skeleton during a person’s subsequent life, it is necessary to promote its maximum increase. Sufficient nutrition is one of the main factors in maintaining bone health. The purpose of our study was to determine the level of daily basic nutrient intake among schoolchildren and to reveal its relationship with clinical disorders of the musculoske­letal system. Materials and methods. Using a computer program, we assessed the actual diet of 65 schoolchildren aged from 8 to 17 years. Results. It was found that 90 % of children were deficient in iodine and calcium, and more than 70 % were deficient in zinc and selenium. The deficiency of potassium, magnesium, iron, copper, fluorine, manganese, and phosphorus was less pronounced. A significant deficiency of vitamin D, β-carotene, vitamin A, biotin, and vitamin E was noted. In almost half of the examined children, the share of saturated fatty acids in the diet exceeds the recommended norm, while the level of polyunsaturated fatty acids is significantly reduced. In 93.8 % of schoolchildren, the nutritional ratio between calcium and phosphorus is disturbed. Conclusions. The obtained results testify to the unbalanced diet of schoolchildren and inconsistency with physiological needs. Deficiency of a number of nutrients can contribute to musculoskeletal pain, convulsive syndrome, fractures, caries and recurrent respiratory di­sease.

Brown fat-specific mitoribosomal function is crucial for preventing cold exposure-induced bone loss

This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT’s metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways.

The Importance of Vitamin K and the Combination of Vitamins K and D for Calcium Metabolism and Bone Health: A Review.

The aim of the present review is to discuss the roles of vitamin K (phylloquinone or menaquinones) and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for the maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated, these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. An adequate vitamin K status is required for the carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanisms, such as menaquinone 4 acting as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through the dietary adequacy of vitamin K. Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3, we find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed.

Racial Comparisons Of Postmenopausal Osteoporosis Between African American And Caucasian Women

Background: Osteoporosis is a chronic degenerative metabolic disease of the skeletal system characterized by decreased bone mineral density (BMD), leading to fragile bones prone to fractures. Postmenopausal osteoporosis is particularly prevalent due to the decline in estrogen levels, a hormone essential for maintaining bone health. This study aims to compare the incidence and risk factors of postmenopausal osteoporosis between African American and Caucasian women, focusing on differences in BMD, risk factors, and the effectiveness of screening and treatment methods. Methods and Materials: This research was conducted at the Southeastern Medical Center, Texas, involving 1,000 postmenopausal women aged 60 or older, with equal representation of 500 African American and 500 Caucasian women. Data collection included demographic information, medical history, and BMD measurements using the General Electric LUNAR DPXIQ Model 2288 DEXA device. Statistical analysis was performed using Chi-square and Fisher's assessment tests to evaluate risk factors such as alcohol intake, smoking, medication usage, and comorbidities. BMI and age evaluations were systematized, and the World Health Organization (WHO) guidelines were used to classify osteoporosis and osteopenia. Results: The study revealed that Caucasian women had higher alcohol intake, family history of fractures, and greater use of vitamins, calcium, and hormonal treatments compared to African American women. Conversely, African American women exhibited higher rates of comorbidities like diabetes mellitus, hyperthyroidism, kidney diseases, and rheumatoid arthritis. Despite starting menopause with higher BMD levels, African American women were less likely to be prescribed medication for low BMD. Screening rates and adherence to recommended treatments also varied significantly between the two groups. Conclusion: The findings highlight significant racial disparities in the incidence, risk factors, and management of postmenopausal osteoporosis. Increasing awareness about osteoporosis and promoting lifestyle modifications such as diet, exercise, and cessation of smoking and alcohol consumption can help mitigate these disparities. Future research should focus on developing targeted interventions to improve screening and treatment adherence among African American women, addressing the specific challenges they face in managing bone health.

The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency.

Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.

Clinical Practice Guidelines of the Latin American Federation of Endocrinology for the use of vitamin D in the maintenance of bone health: recommendations for the Latin American context

IntroductionThese guidelines aim to provide evidence-based recommendations for the supplementation of Vitamin D in maintaining bone health. An unmet need persists in Latin American regarding the availability of clinical and real-world data for rationalizing the use of vitamin D supplementation. The objective of these guidelines is to establish clear and practical recommendations for healthcare practitioners from Latin American countries to address Vitamin D insufficiency in clinical practice.MethodsThe guidelines were developed according to the GRADE-ADOLOPMENT methodology for the adaptation or adoption of CPGs or evidence-based recommendations. A search for high quality CPGs was complemented through a comprehensive review of recent literature, including randomized controlled trials, observational studies, and systematic reviews evaluating the effects of Vitamin D supplementation on bone health. The evidence to decision framework proposed by the GRADE Working Group was implemented by a panel of experts in endocrinology, bone health, and clinical research.ResultsThe guidelines recommend Vitamin D supplementation for individuals aged 18 and above, considering various populations, including healthy adults, individuals with osteopenia, osteoporosis patients, and institutionalized older adults. These recommendations offer dosing regimens depending on an individualized treatment plan, and monitoring intervals of serum 25-hydroxyvitamin D levels and adjustments based on individual results.DiscussionThe guidelines highlight the role of Vitamin D in bone health and propose a standardized approach for healthcare practitioners to address Vitamin D insufficiency across Latin America. The panel underscored the necessity for generating local data and stressed the importance of considering regional geography, social dynamics, and cultural specificities when implementing these guidelines.

Effects of walnut consumption for 2 years on older adults' bone health in the Walnuts and Healthy Aging (WAHA) trial.

Nutritional strategies to maintain bone health in aging individuals are of great interest. Given the beneficial nutrient composition of walnuts, rich in alpha-linolenic (the vegetable n-3 fatty acid) and polyphenols, their regular consumption might be a dietary option to reduce age-related bone loss. We determined whether daily walnut consumption improves bone mineral density (BMD) and circulating biomarkers of bone turnover. The Walnuts and Healthy Aging study (WAHA) is a two-center, parallel, randomized controlled trial evaluating the effect of a diet enriched with walnuts at ≈15% energy compared with a control diet for 2 years on age-related health outcomes in healthy men and women aged 63-79 years. Changes in BMD were a prespecified secondary outcome only at the Barcelona node of the trial, where 352 participants were randomized. Retention rate was 92.6%. Primary endpoints were 2-year changes in BMD at the spine and the nondominant femoral neck, determined by dual-energy X-ray absorptiometry (DXA). Secondary endpoints were 2-year changes in bone turnover biomarkers (adrenocorticotropic hormone, Dickkopf WNT signaling pathway inhibitor-1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, parathyroid hormone, and fibroblast growth factor-23), which were quantified in 211 randomly selected participants. The walnut diet versus the control diet had no effect on 2-year changes in BMD at the spine (0.15% vs. 0.35%, p = 0.632) and femoral neck (-0.90% vs. -0.70%, p = 0.653), or on bone turnover biomarkers. Results were similar in participants treated or not with bone resorption inhibitors or those with or without osteoporosis/osteopenia at inclusion. Compared with the usual diet, a diet enriched with walnuts at 15% of energy for 2 years failed to improve BMD or circulating markers of bone metabolism in healthy older people.

Gut microbial alterations in arginine metabolism determine bone mechanical adaptation

Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.

Unlocking Vitality: A Comprehensive Review of Vitamin D's Impact on Clinical Outcomes in Critically Ill Children.

This comprehensive review explores the multifaceted role of vitamin D (VD) in critically ill children, examining its implications for clinical outcomes. Although this substance has long been known for its function in maintaining bone health, it is now becoming more widely known for its extensive physiological effects, which include immune system and inflammation regulation. Observational research consistently associates VD levels with outcomes like duration of hospitalization, mortality, and illness severity in critically ill pediatric patients. Mechanistically, it exerts anti-inflammatory and endothelial protective effects while modulating the renin-angiotensin system. Increasing VD levels through supplementation presents promise as a therapeutic strategy; however, further research is necessary to elucidate optimal dosage regimens and safety profiles. This review emphasizes the significance of comprehending the intricate relationship between VD and critical illnesses among pediatric populations.