Environmental Impact on Bone Health

Endocrine disruptors are chemicals that alter the synthesis, transport, release, binding, and degradation of natural hormones involved in reproduction and development. Scientific research conducted in recent years has significantly advanced understanding of the health effects of these chemicals. Many endocrine disruptors to which we are unknowingly exposed in our daily lives may affect our tissues, organs, and even bones. When the studies are examined, it is seen that exposure to endocrine-disrupting chemicals (EDCs) even in the prenatal period leads to delayed ossification, growth retardation, changes in bone length and size, and decreases in bone mineral density and mineral content. Information regarding bone health, development, growth, and mineral content reveals that EDCs negatively impact these processes at both clinical and molecular levels. This review addresses the effects of bisphenols, alkylphenols, organotin compounds, dioxins and dioxin-like compounds, phthalate esters, and per- and polyfluoroalkyl substances on bone. The selection of these substances is based on key characteristics such as persistence, environmental prevalence, endocrine activity, and their potential to cause changes in bone development, metabolism, and structural integrity. This review summarizes the effects of endocrine disruptors on bone metabolism, but further research is needed as these mechanisms are not yet fully understood.

An association between seasonal fluctuation ‘cycling’ of 25(OH)D and increased bone resorption but not BMD or BMC in UK South Asian and Caucasian women living at 51on

Diabetes mellitus (T1DM) is associated with increased fracture risk that cannot be fully explained by traditional bone mineral density (BMD) measurements. Emerging evidence suggests that diabetes-induced alterations in bone microarchitecture, remodeling, and mechanoregulation contribute to skeletal fragility. However, the specific structural and functional changes in bone differ between T1DM and T2DM, and the mechanisms underlying these differences remain incompletely understood.Innovation in medical imaging and increasingly accessible computational power have made it possible to monitor changes in bone microarchitecture and measure the mechanical properties of bone via image-based finite element analysis. Moreover, longitudinal clinical studies have also shown that the combined use of high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis can be used to measure load-driven bone remodelling in vivo.This talk will present findings from a meta-analysis of high-resolution peripheral quantitative computed tomography (HR-pQCT) studies assessing diabetes-related differences in bone structure and a longitudinal cohort study, conducted with partners from the FIDELIO – Bone Health in Diabetes Innovative Training Network, examining bone remodeling and mechanoregulation in individuals with type 1 diabetes mellitus (T1DM).The meta-analysis synthesized data from 16 studies, encompassing 743 individuals with diabetes and 3,472 controls, to characterize the impact of T1DM and type 2 diabetes mellitus (T2DM) on bone microarchitecture. Results revealed that T1DM is predominantly associated with adverse trabecular characteristics, whereas T2DM is linked to cortical deficits, with more pronounced deterioration at the radius than at the weight-bearing tibia. These findings suggest that mechanical loading may mitigate some diabetes-associated skeletal changes, emphasizing the role of mechanoregulation in bone fragility.Complementing these insights, a four-year longitudinal cohort study investigated bone remodeling dynamics and responsiveness to mechanical stimuli in individuals with T1DM and diabetic neuropathy. By integrating HR-pQCT imaging with micro-finite element analysis, the study found that T1DM is characterized by lower trabecular bone formation (47% reduction) and resorption (59% reduction) compared to controls. Furthermore, impaired mechanoregulation was evidenced by a reduced likelihood of bone formation and resorption in response to mechanical strain, with these deficits correlating with nerve conduction amplitude and glycated hemoglobin levels.Together, these studies provide a mechanistic understanding of diabetes-associated skeletal fragility, highlighting distinct microarchitectural vulnerabilities in T1DM and T2DM and the role of neuropathy and metabolic control in bone remodeling.

BackgroundSARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper—Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells—DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts—OBs and osteoclasts—OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002–2004 revealed the long-term negative impact (decreased bone mineral density—BMDs) of these infections on bone health.MethodologyWe used the keywords “immunopathogenesis of SARS-CoV-2,” “SARS-CoV-2 and bone cells,” “factors influencing bone health and COVID-19,” “GUT microbiota,” and “COVID-19 and Bone health” to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus.ConclusionCurrent evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota—GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.

Medication-Related Impacts on Pediatric Bone Health

I. Basics of Nutrition and Bone Biology Evolutionary Aspects of Bone Health: Development in Early Human Populations Dorothy A. Nelson, Norman J. Sauer, and Sabrina C. Agarwal Genetics, Nutrition, and Bone Health, Serge Ferrari. Bone Physiology: Bone Cells, Modeling, and Remodeling Lawrence G. Raisz Interpretation of Bone Mineral Density As It Relates to Bone Health and Fracture Risk Leon Lenchik, Sridhar Vatti, and Thomas C. Register Importance of Nutrition in Fracture Healing Sanjeev Kakar and Thomas A. Einhorn Nutritional Assessment of Nutrients for Bone Health Edith M. C. Lau and Winny W. Y. Lau Nutritional Assessment: Analysis of Relations Between Nutrient Factors and Bone Health John J. B. Anderson, Boyd R. Switzer, Paul Stewart, and Michael Symons Nutrition and Oral Bone Status Elizabeth A. Krall II. Nutrition and Bone: Effects of Life Stages and Race Nutrition in Pregnancy and Lactation Bonny L. Specker Nutritional Requirements for Fetal and Neonatal Bone Health and Development Stephanie A. Atkinson Nutrition and Bone Health in Children and Adolescents Velimir Matkovic, Nancy Badenhop-Stevens, Eun-Jeong Ha, Zeljka Crncevic-Orlic, and Albert Clairmont Calcium and Vitamin D for Bone Health in Adults Bess Dawson-Hughes Nutrition and Bone Health in the Elderly Clifford J. Rosen Nutrition and Skeletal Health in Blacks Susan S. Harris III. Effects of Dietary Macronutrients Food Groups and Bone Health Susan A. New Vegetarianism and Bone Health in Women Susan I. Barr Protein Intake and Bone Health Jean-Philippe Bonjour, Patrick Ammann, Thierry Chevalley, and Rene Rizzoli Acid-Base Balance and Bone Health David A. Bushinsky IV. Minerals QuantitativeClinical Nutrition Approaches to the Study of Calcium and Bone Metabolism Connie M. Weaver, Meryl Wastney, and Lisa A. Spence Sodium, Potassium, Phosphorus, and Magnesium Robert P. Heaney Fluoride and Bone Health Johann D. Ringe Lead Toxicity in the Skeleton and Its Role in Osteoporosis J. Edward Puzas, James Campbell, Regis J. O'Keefe, and Randy N. Rosier Microminerals and Bone Health Steven A. Abrams and Ian J. Griffin V. Fat-Soluble Vitamins/Micronutrients Vitamin A and Bone Health Peter Burckhardt Vitamin D Michael F. Holick Vitamin D Utilization in Subhuman Primates: Lessons Learned at the Los Angeles Zoo John S. Adams, Rene F. Chun, Shaoxing Wu, Songyang Ren, Mercedes A. Gacad, and Hong Chen Vitamin K, Oral Anticoagulants, and Bone Health Sarah L. Booth and Anne M. Charette VI. Lifestyle Effects/Supplements Smoking, Alcohol, and Bone Health Douglas P. Kiel Exercise and Bone Health Maria A. Fiatarone Singh Body Weight/Composition and Weight Change: Effects on Bone Health Sue A. Shapses and Mariana Cifuentes Attenuation of Osteoporosis by n-3 Lipids and Soy Protein Gabriel Fernandes Phytoestrogens: Effects on Osteoblasts, Osteoclasts, Bone Markers and Bone Mineral Density Lorraine A. Fitzpatrick VII. Secondary Osteoporosis/Diseases Eating Disorders and Their Effects on Bone Health Madhusmita Misra and Anne Klibanski The Role of Nutrition for Bone Health in Cystic Fibrosis Kimberly O. O'Brien and Michael F. Holick Antiepileptic Drugs and Bone Health Marielle Gascon-Barre Glucocorticoid-Induced Osteoporosis Barbara P. Lukert Index

Exposure to anthropogenic chemicals may indirectly compromise animal health by perturbing the gut microbiota. For example, the widely used herbicide glyphosate can affect the microbiota of honey bees, reducing the abundance of beneficial bacterial species that contribute to immune regulation and pathogen resistance. Previous studies have not addressed how this impact depends on concentration, duration of exposure, or stage of microbiota establishment. Worker bees acquire their microbiota from nestmates early in adult life, when they can also be exposed to chemicals collected by foragers or added to the hives. Here, we investigated how the gut microbiota of honey bees is affected by different concentrations of glyphosate and compared the effects with those caused by tylosin, an antibiotic commonly used to treat hives. We treated newly emerged workers at the stage at which they acquire the microbiota and also workers with established gut microbiota. Treatments consisted of exposure to sucrose syrup containing glyphosate in concentrations ranging from 0.01 mM to 1.0 mM or tylosin at 0.1 mM. Based on 16S rRNA amplicon sequencing and quantitative PCR (qPCR) determination of abundances, glyphosate perturbed the gut microbiota of honey bees regardless of age or period of exposure. Snodgrassella alvi was the most affected bacterial species and responded to glyphosate in a dose-dependent way. Tylosin also perturbed the microbiota, especially at the stage of acquisition, and the effects differed sharply from the effects of glyphosate. These findings show that sublethal doses of glyphosate (0.04 to 1.0 mM) and tylosin (0.1 mM) affect the microbiota of honey bees.IMPORTANCE As is true of many animal species, honey bees depend on their gut microbiota for health. The bee gut microbiota has been shown to regulate the host immune system and to protect against pathogenic diseases, and disruption of the normal microbiota leads to increased mortality. Understanding these effects can give broad insights into vulnerabilities of gut communities, and, in the case of honey bees, could provide information useful for promoting the health of these economically critical insects, which provide us with crop pollination services as well as honey and other products. The bee gut microbiota is acquired early in adult life and can be compromised by antibiotics and other chemicals. The globally used weed killer glyphosate was previously found to impact the gut microbiota of honey bees following sustained exposure. In the present study, we address how this impact depends on concentration, duration of exposure, and stage of community establishment. We found that sublethal doses of glyphosate reduce the abundance of beneficial bacteria and affect microbial diversity in the guts of honey bees, regardless of whether exposure occurs during or after microbiota acquisition. We also compared the effects of glyphosate to those of tylosin, an antibiotic used in beekeeping, and observed that tylosin effects diverge from those caused by glyphosate and are greater during microbiota acquisition. Such perturbations are not immediately lethal to bees but, depending on exposure level, can decrease survivorship under laboratory conditions.

The aim of the present work is to investigate the link between two endocrine disruptor compounds (EDCs), which are chemicals that interfere with the hormone system in human and wildlife, and the human immune response through a study of their effects on the THP-1 human cell line which was used as a model for macrophages. We used two EDCs, diisononylphthalate (DiP) and 4-n-nonylphenol (NP) alone or in combination in order to evaluate the effects of these compounds on several parameters of the immune response - cytokine secretion, phagocytosis and the putative implication of the estrogen receptors - by studying the level of MAPK activation. NP and DiP strongly reduced phagocytosis and modify cytokine secretions. Indeed, differentiated THP-1 cell exposures (i) to 5 and 10 microM of combination of NP and DiP induced an IL-8 level in the medium respectively of 28.9 and 45 percent higher than the level obtained for the control (untreated cells), (ii) to combination of NP and DiP at 10 microM induced an increase of IL-1β level in comparison to the control level, (iii) to combination of NP and DiP induced an increase of TNF-α level whatever the concentration of EDCs tested (between 0 and 10 microM). Lastly, differentiated THP-1 cell exposure to NP, DiP alone or in combination (2 microM for each condition) induced a decrease of ERK1/2 phosphorylation in comparison to ERK1/2 phosphorylation level of the control. Moreover, differentiated THP-1 cell treatments by ICI-182780 (an estrogen receptor antagonist) supressed the EDC effects on ERK1/2 phosphorylation level which indicates an estrogen receptor-dependent pathway. These results suggest that EDCs have the ability to alter the human immune function, maybe by interfering with endocrine balance.

Circulating concentrations of vitamin E isomers: Association with bone turnover and arterial stiffness in post-menopausal women

In this study, we examined the effects of organic types of calcium derived from oyster shell (OS-Ca) and nano-calcium (Nano-Ca) on the bio-availability and physiological responses associated with bone health in ovariectomised rats. Increased body weight, which is one of the physiological effects of ovary removal, was significantly recovered by Nano-Ca treatment (p<0.05). The reduced calcium level in the liver in ovariectomised rat was increased significantly with OS-Ca and Nano-Ca treatment (p<0.05), suggesting improved calcium bio-availability. Alkaline phosphatase (ALP), osteocalcin, and deoxypyridinoline (DPD) were analysed as biochemical markers of bone metabolism and health in the presence or absence of OSCa and Nano-Ca. ALP, osteocalcin, and DPD levels increased following ovary removal and tended to decrease after treatment with Nano-Ca, indicating that Nano-Ca induces favourable bone metabolism. This result was reflected in the recovery of bone mineral density (BMD) and bone mineral content (BMC) of the femur after Nano-Ca treatment following ovary removal. Taken together, our data show that the tested calcium treatments, especially using Nano-Ca, enhanced the bioavailability or absorption of calcium and positively affected bone metabolism in ovariectomised rats.

9610 Background: Weight-bearing exercise may slow the rate of bone loss associated with breast cancer treatment. The purpose of this study is to determine the effect of tai chi chuan (TCC) on bone health, as measured by the changes in the levels of bone resorption and bone formation. This study also aimed to investigate whether changes in bone health were correlated with growth and inflammation markers that serve as regulators of bone cell function. Methods: Female patients (N=16) who completed treatment for breast cancer within the past 30 months were randomly assigned to either the TCC group or the psycho-educational support group without exercise (ST) for 60 minutes, three times a week for a period of 12 weeks. Serum levels of bone resorption (N-telopeptides of type I collagen; NTx) and bone formation (bone specific alkaline phosphatase; BAP) were determined by ELISA at baseline and post-intervention. Using validated methods, a bone remodeling index (BRI) was calculated from levels of NTx and BAP. In addition, pre- and post-intervention levels of insulin-like growth factor binding protein 1 (IGFBP-1) and interleukin-2 (IL-2), markers associated with excessive bone resorption, were measured. Lastly, levels of interleukin-6 (IL-6), believed to enhance bone formation, were measured at both pre- and post-intervention. Results: ANCOVA analyses demonstrated that survivors in the TCC group experienced a greater increase in bone remodeling than those in the ST group (Δ BRITCC=1.6 vs Δ BRIST=0.2; p=0.04). All correlations were determined by Pearson's correlation coefficients. IGFBP-1 was negatively correlated with increasing bone remodeling levels (r=-0.43, p=0.14). IL-2 was also negatively correlated with increasing bone remodeling levels (r=-0.35, p=0.24). IL-6 was positively correlated with increasing bone remodeling levels (r=0.69, p=0.01). Conclusions: This pilot study suggests that TCC has positive effects on bone remodeling through changes in growth and inflammation factors that regulate bone cell function. A larger, more definitive trial examining the influence of TCC on bone remodeling is warranted. Funding: Sally Schindel Cone and R25 CA102618 No significant financial relationships to disclose.

Background and objectivesEslicarbazepine acetate (ESL) is a third-generation anti-seizure medication for patients with focal-onset epilepsy. There are known short-term impacts of classic enzyme-inducing drugs on bone health. For oxcarbazepine, which like ESL is a less potent inducer of cytochrome P450 (CYP450) than carbamazepine, some studies have shown that treatment is associated with increased bone metabolic parameters. The effects of ESL on bone health have not been systematically evaluated so the objective of this study was to investigate whether adverse effects of ESL on bone mineral density (BMD) could be measured after a 12-month exposure period. In addition, the effects of ESL on bone turnover were investigated using laboratory indicators of bone metabolism.MethodsBONAPARTE was a prospective, longitudinal, observational study that enrolled patients with focal-onset epilepsy with or without secondary generalization who started treatment with ESL, either as adjunctive treatment or monotherapy, at two tertiary epilepsy centres in Germany between February 2018 and July 2020. Standardised osteodensitometry and biochemical bone metabolism parameters at the time of ESL initiation and 1 year after continuation of therapy were assessed. Comparisons between biochemical and densitometric parameters at baseline and after 12 months of treatment were performed using the paired samples t test.ResultsIn total, 26 patients (15 male; mean age 41.4 ± 12.5 years) newly treated with ESL were evaluated. Six of these patients had osteopenia at baseline. The mean daily dose of ESL at the 12-month follow-up was 1438 ± 1406 mg. At the group level, there were no significant effects of treatment with ESL on laboratory markers or on BMD. Mean values of BMD in g/cm2 at baseline and after 12 months of ESL treatment were 1.17 (± 0.16) and 1.16 (± 0.16) in the lumbar spine, and 0.98 (± 0.15) and 0.96 (± 0.15) in the proximal femur, respectively. Intra-individually, two patients developed de novo osteopenia measured at the femoral neck associated with relevant changes in bone metabolic parameters.ConclusionNeither osteodensitometry nor bone metabolism parameters showed significant group effects after 1 year of treatment with ESL. Individual fluctuations were observed, however, which may warrant monitoring for longer follow-up periods.The study was registered in the German register for clinical studies under the number DRKS00010430 with the official name BONAPARTE.

Chronic psychological stress is increasingly recognized as a major public health concern, contributing to cardiovascular disease, obesity, asthma, and impaired bone health. Although the mechanisms linking stress to skeletal dysregulation are well characterized in adults, pediatric studies remain limited. Longitudinal and mechanistic studies are needed to clarify how stress affects bone accrual during childhood. Both preclinical and clinical data show that stress can influence bone health through endocrine and immune pathways as well as via altered dietary intake, high or reduced physical activity, medications and disrupted sleep patterns. Elevated stress may also increase oxidative stress, which in turn generates mitochondrial reactive oxygen species (ROS), impairing stem cells differentiation potential, osteoblast and chondrocyte function and suppressing bone formation and growth. In addition, conditions marked by high levels of the pro-inflammatory cytokines TNF-α and IL-6, as well as by elevated exogenous or endogenous glucocorticoids (GCs), further increase cellular oxidative stress. Interventions targeting oxidative stress, such as growth hormone, vitamins C and E, or bisphosphonates, may mitigate skeletal deficits. Here, we review clinical and preclinical evidence on the direct and indirect effects of psychological stress on pediatric bone health.

BACKGROUND AND AIM: One of the main sources of lead (Pb) exposure in Mexico is the use of lead-glazed ceramics (PbC). Exposure to Pb is associated with a decrease in bone mineral density (BMD) and bone mass in adults. Our aim was to evaluate the association between use of PbC and bone health in adult women. METHODS: Our cross-sectional study comprised 101 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. Women reported the use of PbC (yes/no) in the past 3 months. BMD was measured by dual-energy X-ray absorptiometry and bone matrix by ultrasound (speed of sound; SOS). We used z-scores from BDM and SOS to create quantity (normal bone: both z-scores between -1 and 1; less abundant (LA): both -1; and more abundant (MA): both 1) and quality (normal bone: absolute difference between z-scores ≤.5 standard deviations (SD); rigid bone(RB): BMD .5 SD of SOS; softer bone (SB): SOS z-score .5 SD of BMD) indexes for cortical and trabecular bone. Multinomial logistic regressions (normal bone as reference outcome category) were performed to estimate the association between use of PbC and the quantity and quality of cortical and trabecular bone, adjusting for age, menopause, socioeconomic status, physical activity, body mass index and gynoid adiposity. RESULTS:Use of PbC was associated with lower odds of MA cortical bone (OR: 0.28, p=0.05 ) and marginally significant odds of cortical SB (OR: 0.31 p=0.1). Null associations were found for the rest of the bone indexes, however the direction of the estimates were opposite with trabecular bone being 1 whereas cortical bone estimates were 1. CONCLUSIONS:Findings from this pilot study suggest that use of PbC, as a proxy of lead exposure, may influence bone health in midlife and should be examined using a lead biomarker and in a larger sample. KEYWORDS: lead-glazed ceramics, bone health, women

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: A one-year pilot randomized controlled trial in adults with severe burns