Diminished Bone Mineral Density Research Articles

TRIM16 mitigates impaired osteogenic differentiation and antioxidant response in D-galactose-induced senescent osteoblasts

Senile osteoporosis (SOP), characterized by significant bone loss, poses a substantial threat to elderly skeletal health, with oxidative stress playing a crucial role in its pathogenesis. Although Tripartite Motif 16 (TRIM16) has been identified as a promoter of antioxidant response and osteogenic differentiation, its regulatory role in SOP remains incompletely understood. This study aims to elucidate the underlying mechanism of TRIM16 in mitigating D-galactose (D-gal)-induced senescent osteoblasts. Initially, we observed diminished bone mineral density (BMD) and impaired bone microstructure in naturally aging (24 months) and D-gal-induced (18 months) aged mice through Dual-energy X-ray absorptiometry (DEXA), micro-CT, hematoxylin and eosin staining, and Masson staining. Immunohistochemistry analysis revealed downregulation of TRIM16 and osteogenic differentiation markers (Collagen-1, Runx-2, osteopontin) in femur samples of aged mice. Furthermore, in D-gal-induced senescent MC3T3-E1 osteoblasts, we observed the suppression of osteogenic differentiation and maturity, along with cytoskeleton impairment via Alkaline phosphatase (ALP), Alizarin Red S, and Rhodamine-phalloidin staining. The protein expression of TRIM16, osteogenic differentiation markers, and antioxidant indicators (Nrf-2, HO-1, SOD1) decreased, while the production of reactive oxygen species (ROS) significantly increased. Knockdown and overexpression of TRIM16 using lentivirus in osteoblasts revealed that the downregulation of TRIM16 inhibited osteogenic differentiation and induced oxidative stress. Notably, TRIM16 overexpression partially attenuated D-gal-induced inhibition of osteogenic differentiation and increased oxidative stress. These findings suggest TRIM16 may mitigate impaired osteogenic differentiation and antioxidant response in D-gal-induced senescent osteoblasts, suggesting its potential as a therapeutic target for SOP.

The Role of Sport in Human Health: Prevention and Treatment of Osteoporosis

Introduction and purpose Osteoporosis is the most prevalent metabolic bone disease, characterized by diminished bone mineral density, compromised bone microarchitecture, and geometry, culminating in diminished bone strength and susceptibility to fractures. Physical activity posits potential as a preventive measure and therapeutic approach for osteoporosis. The aim of this study was to assess the impact of physical activity on the prevention and treatment of osteoporosis. Materials and method In order to curate appropriate sources for this article, a comprehensive search was conducted within the PubMed and Google Scholar databases. A brief description of the state of knowledge One of the risk factors for osteoporosis is a lack of physical activity. For this reason, many scientists have decided to conduct some research to determine whether physical activity will have a beneficial impact on both the prevention and treatment of osteoporosis. These studies show that physical activity can benefit people with osteoporosis by improving bone density, balance, strength, and overall physical function. Regular and long-term exercise is essential to maximize these benefits. Summary The studies conducted so far provide promising results and confirm the beneficial impact of physical exercises on people with osteoporosis as well as on the prevention of this disease. Exercises should be performed regularly and persistently.

Geriatric trauma: there is more to it than just the implant!

Geriatric trauma continues to rise, corresponding with the continuing growth of the older population. These fractures continue to expand, demonstrated by the incidence of hip fractures having grown to 1.5 million adults worldwide per year. This patient population and their associated fracture patterns present unique challenges to the surgeon, as well as having a profound economic impact on the health care system. Pharmacologic treatment has focused on prevention, with aging adults having impaired fracture healing in addition to diminished bone mineral density. Intraoperatively, novel ideas to assess fracture reduction to facilitate decreased fracture collapse have recently been explored. Postoperatively, pharmacologic avenues have focused on future fracture prevention, while shared care models between geriatrics and orthopaedics have shown promise regarding decreasing mortality and length of stay. As geriatric trauma continues to grow, it is imperative that we look to optimize all phases of care, from preoperative to postoperative.

Serum Human \(\beta\) Defensin (HBD-2) and Osteocalcin Levels in Menopausal Iraqi Women with Osteopenia

Background and Purpose: Osteopenia (OP) is a chronic and advanced condition that is often described by diminished bone mineral density (BMD), deteriorated bone tissue microarchitecture, and an elevated risk of fracture. The low molecular weight antimicrobial peptides known as Human Defensin (HBD-2) proteins are produced locally by keratinocytes in various tissues, including skin, mucosa, and bones. Osteocalcin, often called bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a tiny (49 amino acids) noncollagenous protein hormone in bone and dentin. It was initially discovered to be a calcium-binding protein. Material and Methods: Prospective study to evaluate the osteoblast's ability to produce and release osteocalcin makes it a noncollagenous protein, and has primary physiological roles include calcium ion homeostasis, maintaining an average rate of bone mineralization, preventing the aberrant development of hydroxyapatite crystals, and participating in bone remodeling via a negative feedback loop. In menopausal women with osteopenia, this study evaluates the osteocalcin and human beta-defensin 2 for their diagnostic potential. A small amount of venous blood, about 5 ml, was added to the tube and centrifuged for five minutes at a speed of 3 \(\times\) 103 rpm. The serum was put into an Eppendorf tube and stored in a freezer at -20 \(^\circ\)C before being tested. With the help of the specified equation, the body mass index is determined. Findings and Conclusion: Increasing serum HBD 2, osteocalcin levels in postmenopausal women with osteopenia plays an essential role in developing osteopenia to osteoporosis. Differences in serum levels of alkaline phosphatase were seen among patients (as a sample) and controls; serum levels of HBD2 and osteocalcin were considerably lower in controls than in patients (p 0.01).

Associations among gene polymorphisms, crestal bone loss, and bone mineral density in patients receiving dental implants

ObjectivesInterleukin 1 (IL-1) and interleukin 6 (IL-6) gene polymorphisms have been suggested to be responsible for diminished bone mineral density (BMD) and high crestal bone loss (CBL) in some individuals. However, the effects of systemic BMD on variations in peri-implant CBL are unclear. Hence, this study was aimed at investigating the association of IL-1 and IL-6 gene polymorphisms with systemic BMD and CBL around dental implants. MethodsA total of 190 participants undergoing dental implantation in the mandibular posterior region were selected according to predetermined selection criteria and divided into a normal BMD group (NBD, 93 participants, T-score ≥ −1) and low BMD group (LBD, including both osteoporosis and osteopenia, 97 participants, T-score < −1 standard deviation) according to the BMD of the right femoral neck, measured with dual-energy X-ray absorptiometry. Dental implants were placed through the standard surgical protocol, and CBL was calculated after 6 months with cone beam computed tomography scans before second-stage surgery. Genotyping was performed on all participants for IL-1A-889 A/G, IL-1B-511G/A, IL-1B+3954, and IL-6-572 C/G gene polymorphisms. ResultsThe demographic and clinical characteristics of the participants in both groups were compared with t-test and chi-square test (χ2). The associations of NBD and LBD with the different genotypes and CBL was determined with odds ratios, and p < 0.05 was considered statistically significant. The frequency of IL-1B-511AA and IL-6-572 GG genotypes was significantly higher in LBD than in NBD (p < 0.05). In LBD, the IL-1B-511 AA (AA vs GA + GG; p ≤ 0.001) and IL-6-572 GG (GG vs CC + GC; p = 0.001) genotypes were significantly associated with higher peri-implant CBL. ConclusionsIndividuals with the IL-1B-511 AA or IL-6-572 GG genotype had elevated risk of osteoporosis/osteopenia and were more susceptible to CBL around dental implants.

Hormone Replacement Therapy Does Not Eliminate Risk Factors for Joint Complications following Total Joint Arthroplasty: A Matched Cohort Study

Aging causes a reduction in testosterone and estrogen, which is linked to diminished bone mineral density. Hormone replacement therapy and its effect on the outcome of joint arthroplasties is unclear. The purpose of this study was to analyze the impact of testosterone replacement therapy (TRT) and estrogen replacement therapy (ERT) on the medical and joint outcomes of total hip (THA) and total knee arthroplasties (TKA). A retrospective cohort study was conducted using the PearlDiver database. Patients who received TRT or ERT perioperatively were matched to controls. Rates of 90-day medical complications and 2-year joint complications were queried. Patients who received TRT had an increased risk of revision, periprosthetic joint infection, and pooled joint complications within 2 years following a THA and increased rates of septic and aseptic revisions, and aseptic loosening after TKA compared to the control cohort. Patients receiving ERT had increased rates of aseptic loosening and pooled joint complications within 2 years following THA and increased rates of all-cause revisions and pooled joint complications after TKA. Patients who received TRT demonstrated significantly higher rates of revision rates and PJI. Patients who received perioperative ERT were significantly more likely to have increased risks of revision rates and joint infections.

Risk of ozone exposure-induced fracture.

Ozone (O3) is known to induce oxidative stress that influences various cells and tissues, which may further lead to diminished bone mineral density. Nevertheless, few studies have investigated the association between O3 exposure and fractures. Considering the similar growing trends of O3 concentrations and fracture morbidity in recent years, in the present study, we aimed to examine whether O3 exposure is associated with the fracture morbidity. Using a retrospective cohort study design, we analyzed the records of 8,075 patients with fracture admitted in the warm season to Beijing Jishuitan Hospital from 2014 to 2019 and matched them to the corresponding exposure time and concentration of O3. The results showed that increased odds of fracture were associated with increased O3 concentrations, presumably because O3 induces oxidative stress (OS) that leads to bone mineral density (BMD) loss. Our findings suggest that O3 exposure is a risk factor for fractures, providing new evidence of the adverse health effect induced by air pollution. We can conclude that more intensive air pollution control is needed for the prevention of fracture occurrence.

Evaluation of oral implant survival rate in postmenopausal women with osteopenia/osteoporosis. A retrospective pilot study

BackgroundImplant placement is a common part of dental rehabilitation in older individuals. The role of diminished bone mineral density on the healing of dental implants remains to be elucidated. ObjectiveThe aim of this study was to assess the implant survival rate in postmenopausal women with osteopenia/osteoporosis. MethodsA retrospective cohort study was conducted of postmenopausal women treated with dental implants and stratified into two groups: those receiving antiresorptive therapy (W ≥ 50 years S) or those not receiving treatment (W ≥ 50 years U). The predictor variable was osteopenia/osteoporosis treatment. The outcome variable was implant failure rate at stage two uncovering. Other study variables included: age, implant location, and bone graft placement. T-test, chi-square test, and univariate and multivariate logistic regression were computed. A p-value<0.05 was considered statistically significant. ResultsThe sample was composed of 93 W ≥ 50 years U (197 implants) and 114 W ≥ 50 years S (189 implants). W ≥ 50 years U showed a statistically higher implant failure rate with chi-square testing compared to W ≥ 50 years S (p=0.022). However, univariate, and multivariate logistic regression between age, location, bone grafting, and implant failure did not demonstrate significant associations. ConclusionBoth groups integrated dental implants successfully, with a low failure rate. Implant location, bone grafting, and osteopenia/osteoporosis treatment did not significantly affect osseointegration at uncovering.

Management of Osteoporosis and Spinal Fractures: Contemporary Guidelines and Evolving Paradigms.

Physicians involved in treating spine fractures secondary to osteopenia and osteoporosis should know the pathogenesis and current guidelines on managing the underlying diminished bone mineral density, as worldwide fracture prevention campaigns are trailing behind in meeting their goals. This is a narrative review exploring the various imaging and laboratory tests used to diagnose osteoporotic fractures and a comprehensive compilation of contemporary medical and surgical management. We have incorporated salient recommendations from the Endocrine Society, the American Association of Clinical Endocrinology (AACE), and the American Society for Bone and Mineral Research (ASBMR). The use of modern scoring systems such as Fracture Risk Assessment Tool (FRAX®) for evaluating fracture risk in osteoporosis with a 10-year probability of hip fracture and major fractures in the spine, forearm, hip, or shoulder is highlighted. This osteoporosis risk assessment tool can be easily incorporated into the preoperative bone health optimization strategies, especially before elective spine surgery in osteoporotic patients. The role of primary surgical intervention for vertebral compression fracture and secondary fracture prevention with pharmacological therapy is described, with randomized clinical trial-based wisdom on its timing and dosage, drug holiday, adverse effects, and relevant evidence-based literature. We also aim to present an evidence-based clinical management algorithm for treating osteoporotic vertebral body compression fractures, tumor-induced osteoporosis, or hardware stabilization in elderly trauma patients in the setting of their impaired bone health. The recent guidelines and recommendations on surgical intervention by various medical societies are covered, along with outcome studies that reveal the efficacy of cement augmentation of vertebral compression fractures via vertebroplasty and balloon kyphoplasty versus conservative medical management in the elderly population.

Attention deficit hyperactivity disorder medications and bone mineral density of adults in the United States

IntroductionSeveral medications used to treat attention deficit hyperactivity disorder (ADHD) have been associated with diminished bone mineral density (BMD) in children. The objective of this study was to determine if evidence exists for a similar association among adults. Materials and methodsA retrospective cross-sectional analysis was conducted using data collected by the National Health Nutrition Examination Survey 2013–2018. Data from 7961 individuals aged 18 to 50, 79 of whom were taking medications to treat ADHD. Dual-energy X-ray absorptiometry scans provided measure of body composition. Linear regression models were used to examine associations between ADHD medication use and body composition. ResultsStimulant ADHD medication usage was found to be associated with decreased BMD in both the skull (−6.6%; 95% CI 5.9–7.2) (P < 0.05) and thoracic spine (−6.0%; 95% CI 5.1–7.0) (P < 0.05). No difference in BMD was seen in any other skeletal region based on stimulant ADHD medication use (P > 0.05). We found no evidence to suggest that duration of use affected the observed decreases in BMD, P > 0.05. ConclusionThis study using a nationally representative sample assessed whether stimulant medication use in adults with ADHD was associated with decreased BMD. The overall results are inconclusive. Further study is needed to better evaluate if ADHD and/or stimulant medication use is independently associated with bone health.

Oxidative Stress and Osteoporosis.

Oxidative stress has been implicated as a causative factor in many disease states, possibly including the diminished bone mineral density in osteoporosis. Understanding the effects of oxidative stress on the development of osteoporosis may lead to further research improving preventative and therapeutic measures that can combat this important contributor to morbidity and mortality worldwide. A diet rich in whole plant foods with high antioxidant content along with antioxidant-preserving lifestyle changes may improve bone mineral density and reduce the risk of fragility-related fractures. While it is not explicitly clear if antioxidant activity is the effector of this change, the current evidence supports this possibility. Supplementation with isolated antioxidants may also provide some osteoprotective benefits, but whole plant food-derived antioxidants potentially have more overall benefits. Larger-scale clinical trials are needed to give credence to definitive clinical recommendations.

Hypogonadism and cancer survivorship

Hypogonadism is highly prevalent among not only patients with a history of prior treatment for cancer, but also among those patients with a new oncologic diagnosis who have not yet received any cancer therapy. Hypogonadism can cause a wide array of signs and symptoms including: deceased muscle mass; increased fat mass; decreased energy, mood, and overall sense of well being; diminished bone mineral density; infertility; and impaired libido and sexual function. This purpose of this manuscript is to review the mechanisms by which cancer and oncologic treatment regimens can adversely affect the hypothalamic pituitary gonadal axis, resulting in hypogonadism. Risks and benefits associated with the treatment of testosterone deficiency are also discussed, which are important considerations for clinicians caring for affected patients. Hypogonadism has a high prevalence in the setting of cancer and is an important survivorship issue. Recent randomized controlled trials confirm testosterone's therapeutic benefits in terms of sexual function, mood body composition, and bone health, but the specific benefits in terms of quality of life are less clear. More prospective studies are needed to further delineate the risks, benefits, and overall outcomes of testosterone replacement therapy in patients with cancer and cancer survivors.

Bone Metabolism Alterations in Patients with Common Variable Immune Deficiency: A Retrospective Cohort Study

Objective: Common variable immunodeficiency (CVID) is a relatively frequent primary immunodeficiency disorder characterized by impaired B cell differentiation with hypogammaglobulinemia in the European Society for Immunodeficiencies (ESID) registry system. Increased inflammatory cytokines, prolonged and/or recurrent infections, gastrointestinal complications, and anti-inflammatory medications are risk factors for diminished bone mineral density (BMD) in CVID patients. Materials and Methods: The study group included 32 patients with CVID (19 males and 13 females; mean age: 37.33 ± 13.70 years, 40.6% female), who had been followed up on a regular basis for a period of four years. The patients were categorized into two groups according to their BMD: low BMD and normal BMD. Results: Seventeen patients (8 females and 9 males) had normal BMD (mean age 34.94 ± 11.41 years, 47.1% female) and fifteen patients (5 females and 10 males) had low BMD (mean age 40.03 ± 15.87 years, 33.3% female). In the low BMD group, three patients had osteoporosis and 12 patients had osteopenia. Univariate regression analysis revealed that lymphopenia (odds ratio, OR:6.562, 95% confidence interval, CI: 1.095-39.324, p=0.039) was significantly associated with low BMD. Multivariate regression analysis showed that higher alkaline phosphatase (ALP) levels (OR:1.017, 95% CI 1.001-1.033, p=0.041), lymphopenia (OR:11.028, 95% CI 1.326-91.709, p=0.026), and lower folic acid levels (OR:1.284, 95% CI 1.007-1.637, p=0.043) were also independent predictors for low BMD. Conclusion: Even with some limitations such as the small number for the study population, a single center experience, and a crosssectional design, we recommend that clinical immunologists should be alert for diminished BMD in CVID patients, especially those with low folic acid and high ALP levels and lymphopenia.

The old sheep: a convenient and suitable model for senile osteopenia.

Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10years; n = 41) and young animals (2-4years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.

The natural history of classic galactosemia: lessons from the GalNet registry

BackgroundClassic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients.MethodsObservational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018.ResultsMost affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome.ConclusionThis study describes the natural history of classic galactosemia based on the hitherto largest data set.

Bone disorders associated with diabetes mellitus and its treatments.

Both type 1 and type 2 diabetes mellitus are associated with bone disorders, albeit via different mechanisms. Early studies in patients with type 1 diabetes suggested a 10-fold increase in the hip fracture risk compared to non-diabetic controls. Meta-analyses published more recently indicate a somewhat smaller risk increase, with odds ratios of 6 to 7. Diminished bone mineral density is among the contributors to the increased fracture risk. Both types of diabetes are associated with decreased bone strength related to low bone turnover. The multiple and interconnected pathophysiological mechanisms underlying the bone disorders seen in type 1 diabetes include insulin deficiency, accumulation of advanced glycation end products, bone microarchitecture alterations, changes in bone marrow fat content, low-grade inflammation, and osteocyte dysfunction. The bone alterations are less severe in type 2 diabetes. Odds ratios for hip fractures have ranged across studies from 1.2 to 1.7, and bone mineral density is higher than in non-diabetic controls. The odds ratio is about 1.2 for all bone fragility fractures combined. The pathophysiological mechanisms are complex, particularly as obesity is very common in patients with type 2 diabetes and is itself associated with an increased risk of fractures at specific sites (humerus, tibia, and ankle). The main mechanisms underlying the bone fragility are an increase in the risk of falls, sarcopenia, disorders of carbohydrate metabolism, vitamin D deficiency, and alterations in cortical bone microarchitecture and bone matrix. The medications used to treat both types of diabetes do not seem to play a major role. Nevertheless, thiazolidinediones and, to a lesser extent, sodium-glucose cotransporter inhibitors may have adverse effects on bone, whereas metformin may have beneficial effects. For the most part, the standard management of bone fragility applies to patients with diabetes. However, emphasis should be placed on preventing falls, which are particularly common in this population. Finally, there is some evidence to suggest that anti-fracture treatments are similarly effective in patients with and without diabetes.

LDL TEROKSIDASI DAN KEPADATAN MINERAL TULANG (Oxidized LDL Cholesterol and Bone Mineral Density)

Osteoporosis is defined by low bone density and micro architectural deterioration of bone tissue with a consequent increase in bonefragility and risk of fracture. Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis, which need special device,and expensive fee. So it is not routinely done, therefore another type of examination methods is needed. Oxidized LDL (oxLDL) cholesterolis the parameter correlated with diminished bone mineral density by affecting osteoblast and osteoclast. The aim of this study was toknow the role of oxLDL in diminished bone mineral density by analyzing it. Cross sectional study was held on 78 subjects during theperiod of October 2011 until June 2013 using the primary data from 30−60 years women population in Makassar, whose FPG, ALT,AST, urea and creatinine are within normal limit. Using oxLDL 6.8mU/L value as cut off, had found odds ratio increase 2.2 times with68.8% probability to suffer diminished BMD. Receiver Operating Characteristic (ROC) analysis show area under curve is 60.8%, using8.05mU/L as a cut off point resulting 68.8% sensitivity, 59.2% specifity, 76.1% positive predictive value, 50% negative predictive value,1.71 positive likelihood ratio, 0.53 negative likelihood ratio and 65.4% accuracy. Concluded that oxLDL ≥6.8mU/L increases risk tosuffer diminished BMD 2.2 times. As a diagnostic marker, oxLDL has a weak diagnostic strength and accuracy (68.8% sensitivity and59.2% specifity). The researchers have the opinion to perform a further study with larger and various population, concern on oxLDLbio availability and use it with another parameter as a panel test.

Nuclear receptor and VEGF pathways for gene-blood lead interactions, on bone mineral density, in Korean smokers.

Osteoporosis has a complex etiology and is considered a multifactorial polygenic disease, in which genetic determinants are modulated by hormonal, lifestyle, environmental, and nutritional factors. Therefore, investigating these multiple factors, and the interactions between them, might lead to a better understanding of osteoporosis pathogenesis, and possible therapeutic interventions. The objective of this study was to identify the relationship between three blood metals (Pb, Cd, and Al), in smoking and nonsmoking patients’ sera, and prevalence of osteoporosis. In particular, we focused on gene-environment interactions of metal exposure, including a dataset obtained through genome-wide association study (GWAS). Subsequently, we conducted a pathway-based analysis, using a GWAS dataset, to elucidate how metal exposure influences susceptibility to osteoporosis. In this study, we evaluated blood metal exposures for estimating the prevalence of osteoporosis in 443 participants (aged 53.24 ± 8.29), from the Republic of Korea. Those analyses revealed a negative association between lead blood levels and bone mineral density in current smokers (p trend <0.01). By further using GWAS-based pathway analysis, we found nuclear receptor (FDR<0.05) and VEGF pathways (FDR<0.05) to be significantly upregulated by blood lead burden, with regard to the prevalence of osteoporosis, in current smokers. These findings suggest that the intracellular pathways of angiogenesis and nuclear hormonal signaling can modulate interactions between lead exposure and genetic variation, with regard to susceptibility to diminished bone mineral density. Our findings may provide new leads for understanding the mechanisms underlying the development of osteoporosis, including possible interventions.

Multiscale characterization of cortical bone composition, microstructure, and nanomechanical properties in experimentally induced osteoporosis.

Cortical bone plays a vital role in determining overall bone strength. We investigate the structural, compositional, and nanomechanical properties of cortical bone following ovariectomy (OVX) of 12-week-old Sprague Dawley rats, since this animal model is frequently employed to evaluate the performance of implantable biomaterials in compromised bone healing conditions. Morphological parameters and material properties of bone in the geometrical center of the femoral cortex were investigated four and eight weeks post-OVX and in unoperated controls (Ctrl), using X-ray micro-computed tomography, backscattered electron scanning electron microscopy, Raman spectroscopy, and nanoindentation. The OVX animals showed increase in body weight, diminished bone mineral density, increased intracortical porosity, but increased bone mass through periosteal apposition (e.g., increases in periosteal perimeter, cortical cross-sectional thickness, and cross-sectional area). However, osteocyte densities, osteocyte lacunar dimensions, and the nanomechanical behavior on the single mineralized collagen fibril level remained unaffected. Our correlative multiscale investigation provides structural, chemical, and nanomechanical evidence substantiating earlier reports suggesting that rats ovariectomized at 12 weeks undergo simultaneous bone loss and growth, resulting in the effects of OVX being less obvious. Periosteal apposition contradicts the conventional view of bone loss in osteoporosis but appears advantageous for the greater functional demand imposed on the skeleton by increased body weight and fragility induced by increased intracortical porosity. Through a variety of morphological changes, it is likely that 12-week-old rats are able to adapt to OVX-related microstructural and compositional alterations. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 997-1007, 2018.

Homeostatic Expansion of CD4+ T Cells Promotes Cortical and Trabecular Bone Loss, Whereas CD8+ T Cells Induce Trabecular Bone Loss Only.

Bone loss occurs in human immunodeficiency virus (HIV) infection but paradoxically is intensified by HIV-associated antiretroviral therapy (ART), resulting in an increased fracture incidence that is largely independent of ART regimen. Inflammation in the bone microenvironment associated with T-cell repopulation following ART initiation may explain ART-induced bone loss. Indeed, we have reported that reconstitution of CD3+ T cells in immunodeficient mice mimics ART-induced bone loss observed in humans. In this study, we quantified the relative effects of CD4+ and CD8+ T-cell subsets on bone. T-cell subsets in T-cell receptor β knockout mice were reconstituted by adoptive transfer with CD4+ or CD8+ T-cells subsets were reconstituted in T-cell receptor β knockout mice by adoptive transfer, and bone turnover, bone mineral density, and indices of bone structure and turnover were quantified. Repopulating CD4+ but not CD8+ T cells significantly diminished bone mineral density. However, micro-computed tomography revealed robust deterioration of trabecular bone volume by both subsets, while CD4+ T cells additionally induced cortical bone loss. CD4+ T-cell reconstitution, a key function of ART, causes significant cortical and trabecular bone loss. CD8+ T cells may further contribute to trabecular bone loss in some patients with advanced AIDS, in whom CD8+ T cells may also be depleted. Our data suggest that bone densitometry used for assessment of the condition of bone in humans may significantly underestimate trabecular bone damage sustained by ART.