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Sample records for advanced bone age

  1. IN SITU ACCUMULATION OF ADVANCED GLYCATION ENDPRODUCTS (AGES) IN BONE MATRIX AND ITS CORRELATION WITH OSTEOCLASTIC BONE RESORPTION

    PubMed Central

    Dong, X. Neil; Qin, An; Xu, Jiake; Wang, Xiaodu

    2011-01-01

    Advanced glycation end products (AGEs) have been observed to accumulate in bone with increasing age and may impose effects on bone resorption activities. However, the underlying mechanism of AGEs accumulation in bone is still poorly understood. In this study, human cortical bone specimens from young (31±6 years old), middle-aged (51±3 years old) and elderly (76±4 years old) groups were examined to determine the spatial-temporal distribution of AGEs in bone matrix and its effect on bone resorption activities by directly culturing osteoclastic cells on bone slices. The results of this study indicated that the fluorescence intensity (excitation wave length 360 nm and emission wave length 470±40 nm) could be used to estimate the relative distribution of AGEs in bone (pentosidine as its marker) under an epifluorescence microscope. Using the fluorescence intensity as the relative measure of AGEs concentration, it was found that the concentration of AGEs varied with biological tissue ages, showing the greatest amount in the interstitial tissue, followed by the old osteons, and the least amount in newly formed osteons. In addition, AGEs accumulation was found to be dependent on donor ages, suggesting that the younger the donor the less AGEs were accumulated in the tissue. Most interestingly, AGEs accumulation appeared to initiate from the region of cement lines, and spread diffusively to the other parts as the tissue aged. Finally, it was observed that the bone resorption activities of osteoclasts were positively correlated with the in situ concentration of AGEs and such an effect was enhanced with increasing donor age. These findings may help elucidate the mechanism of AGEs accumulation in bone and its association with bone remodeling process. PMID:21530698

  2. Genetics of aging bone.

    PubMed

    Adams, Douglas J; Rowe, David W; Ackert-Bicknell, Cheryl L

    2016-08-01

    With aging, the skeleton experiences a number of changes, which include reductions in mass and changes in matrix composition, leading to fragility and ultimately an increase of fracture risk. A number of aspects of bone physiology are controlled by genetic factors, including peak bone mass, bone shape, and composition; however, forward genetic studies in humans have largely concentrated on clinically available measures such as bone mineral density (BMD). Forward genetic studies in rodents have also heavily focused on BMD; however, investigations of direct measures of bone strength, size, and shape have also been conducted. Overwhelmingly, these studies of the genetics of bone strength have identified loci that modulate strength via influencing bone size, and may not impact the matrix material properties of bone. Many of the rodent forward genetic studies lacked sufficient mapping resolution for candidate gene identification; however, newer studies using genetic mapping populations such as Advanced Intercrosses and the Collaborative Cross appear to have overcome this issue and show promise for future studies. The majority of the genetic mapping studies conducted to date have focused on younger animals and thus an understanding of the genetic control of age-related bone loss represents a key gap in knowledge. PMID:27272104

  3. Aging and Bone

    PubMed Central

    Boskey, A.L.; Coleman, R.

    2010-01-01

    Bones provide mechanical and protective function, while also serving as housing for marrow and a site for regulation of calcium ion homeostasis. The properties of bones do not remain constant with age; rather, they change throughout life, in some cases improving in function, but in others, function deteriorates. Here we review the modifications in the mechanical function and shape of bones, the bone cells, the matrix they produce, and the mineral that is deposited on this matrix, while presenting recent theories about the factors leading to these changes. PMID:20924069

  4. Recent advances in bone tissue engineering scaffolds

    PubMed Central

    Bose, Susmita; Roy, Mangal; Bandyopadhyay, Amit

    2012-01-01

    Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, biodegradable materials that harbor different growth factors, drugs, genes or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. PMID:22939815

  5. Bone age in cerebral palsy

    PubMed Central

    Miranda, Eduardo Régis de Alencar Bona; Palmieri, Maurício D'arc; de Assumpção, Rodrigo Montezuma César; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patrícia Maria de Moraes Barros

    2013-01-01

    Objective To compare the chronological age and bone age among cerebral palsy patients in the outpatient clinic and its correlation with the type of neurological involvement, gender and functional status. Methods 401 patients with spastic cerebral palsy, and ages ranging from three months to 20 years old, submitted to radiological examination for bone age and analyzed by two independent observers according Greulich & Pyle. Results In the topographic distribution, there was a significant delay (p<0.005) in tetraparetic (17.7 months), hemiparetic (10.1 months), and diparetic patients (7.9 months). In the hemiparetic group, the mean bone age in the affected side was 96.88 months and the uncompromised side was 101.13 months (p<0.005). Regarding functional status, the ambulatory group showed a delay of 18.73 months in bone age (p<0.005). Comparing bone age between genders, it was observed a greater delay in males (13.59 months) than in females (9.63 months), but not statistically significant (p = 0.54). Conclusion There is a delay in bone age compared to chronological age influenced by the topography of spasticity, functional level and gender in patients with cerebral palsy. Level of Evidence IV, Case Series. PMID:24453693

  6. Bone Tissue Engineering: Recent Advances and Challenges

    PubMed Central

    Amini, Ami R.; Laurencin, Cato T.; Nukavarapu, Syam P.

    2013-01-01

    The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field. PMID:23339648

  7. Low-Magnitude Mechanical Stimulation to Improve Bone Density in Persons of Advanced Age: A Randomized, Placebo-Controlled Trial.

    PubMed

    Kiel, Douglas P; Hannan, Marian T; Barton, Bruce A; Bouxsein, Mary L; Sisson, Emily; Lang, Thomas; Allaire, Brett; Dewkett, Dawn; Carroll, Danette; Magaziner, Jay; Shane, Elizabeth; Leary, Elizabeth Teng; Zimmerman, Sheryl; Rubin, Clinton T

    2015-07-01

    Nonpharmacologic approaches to preserve or increase bone mineral density (BMD) include whole-body vibration (WBV), but its efficacy in elderly persons is not clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV (0.3g at 37 Hz) in seniors recruited from 16 independent living communities. The primary outcomes were volumetric BMD of the hip and spine measured by quantitative computed tomography (QCT) and biochemical markers of bone turnover. We randomized 174 men and women (89 active, 85 placebo) with T-scores -1 to -2.5 who were not taking bone active drugs and had no diseases affecting the skeleton (mean age 82 ± 7 years, range 65 to 102). Participants received daily calcium (1000 mg) and vitamin D (800 IU). Study platforms were activated using radio frequency ID cards providing electronic adherence monitoring; placebo platforms resembled the active platforms. In total, 61% of participants in the active arm and 73% in the placebo arm completed 24 months. The primary outcomes, median percent changes (interquartile range [IQR]) in total volumetric femoral trabecular BMD (active group (2.2% [-0.8%, 5.2%]) versus placebo 0.4% [-4.8%, 5.0%]) and in mid-vertebral trabecular BMD of L1 and L2 (active group (5.3% [-6.9%, 13.3%]) versus placebo (2.4% [-4.4%, 11.1%]), did not differ between groups (all p values > 0.1). Changes in biochemical markers of bone turnover (P1NP and sCTX) also were not different between groups (p = 0.19 and p = 0.97, respectively). In conclusion, this placebo-controlled randomized trial of daily WBV in older adults did not demonstrate evidence of significant beneficial effects on volumetric BMD or bone biomarkers; however, the high variability in vBMD changes limited our power to detect small treatment effects. The beneficial effects of WBV observed in previous studies of younger women may not occur to the same extent in

  8. Bone Mineral Density in Healthy Female Adolescents According to Age, Bone Age and Pubertal Breast Stage

    PubMed Central

    Moretto, M.R; Silva, C.C; Kurokawa, C.S; Fortes, C.M; Capela, R.C; Teixeira, A.S; Dalmas, J.C; Goldberg, T.B

    2011-01-01

    Objectives: This study was designed to evaluate bone mineral density (BMD) in healthy female Brazilian adolescents in five groups looking at chronological age, bone age, and pubertal breast stage, and determining BMD behavior for each classification. Methods: Seventy-two healthy female adolescents aged between 10 to 20 incomplete years were divided into five groups and evaluated for calcium intake, weight, height, body mass index (BMI), pubertal breast stage, bone age, and BMD. Bone mass was measured by bone densitometry (DXA) in lumbar spine and proximal femur regions, and the total body. BMI was estimated by Quetelet index. Breast development was assessed by Tanner’s criteria and skeletal maturity by bone age. BMD comparison according to chronologic and bone age, and breast development were analyzed by Anova, with Scheffe’s test used to find significant differences between groups at P≤0.05. Results: BMD (g·cm-2) increased in all studied regions as age advanced, indicating differences from the ages of 13 to 14 years. This group differed to the 10 and 11 to 12 years old groups for lumbar spine BMD (0.865±0.127 vs 0.672±0.082 and 0.689±0.083, respectively) and in girls at pubertal development stage B3, lumbar spine BMD differed from B5 (0.709±0.073 vs 0.936±0.130) and whole body BMD differed from B4 and B5 (0.867±0.056 vs 0.977±0.086 and 1.040±0.080, respectively). Conclusion: Bone mineralization increased in the B3 breast maturity group, and the critical years for bone mass acquisition were between 13 and 14 years of age for all sites evaluated by densitometry. PMID:21966336

  9. Bone age assessment meets SIFT

    NASA Astrophysics Data System (ADS)

    Kashif, Muhammad; Jonas, Stephan; Haak, Daniel; Deserno, Thomas M.

    2015-03-01

    Bone age assessment (BAA) is a method of determining the skeletal maturity and finding the growth disorder in the skeleton of a person. BAA is frequently used in pediatric medicine but also a time-consuming and cumbersome task for a radiologist. Conventionally, the Greulich and Pyle and the Tanner and Whitehouse methods are used for bone age assessment, which are based on visual comparison of left hand radiographs with a standard atlas. We present a novel approach for automated bone age assessment, combining scale invariant feature transform (SIFT) features and support vector machine (SVM) classification. In this approach, (i) data is grouped into 30 classes to represent the age range of 0- 18 years, (ii) 14 epiphyseal ROIs are extracted from left hand radiographs, (iii) multi-level image thresholding, using Otsu method, is applied to specify key points on bone and osseous tissues of eROIs, (iv) SIFT features are extracted for specified key points for each eROI of hand radiograph, and (v) classification is performed using a multi-class extension of SVM. A total of 1101 radiographs of University of Southern California are used in training and testing phases using 5- fold cross-validation. Evaluation is performed for two age ranges (0-18 years and 2-17 years) for comparison with previous work and the commercial product BoneXpert, respectively. Results were improved significantly, where the mean errors of 0.67 years and 0.68 years for the age ranges 0-18 years and 2-17 years, respectively, were obtained. Accuracy of 98.09 %, within the range of two years was achieved.

  10. Determinants of muscle and bone aging

    PubMed Central

    Curtis, E; Litwic, A; Cooper, C; Dennison, E

    2015-01-01

    Loss of bone and muscle with advancing age represent a huge threat to loss of independence in later life. Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip, spine and distal forearm. Sarcopenia, the age related loss of muscle mass and function, may add to fracture risk by increasing falls risk. In the context of muscle aging, it is important to remember that it is not just a decline in muscle mass which contributes to the deterioration of muscle function. Other factors underpinning muscle quality come into play, including muscle composition, aerobic capacity and metabolism, fatty infiltration, insulin resistance, fibrosis and neural activation. Genetic, developmental, endocrine and lifestyle factors, such as physical activity, smoking and poor diet have dual effects on both muscle and bone mass in later life and these will be reviewed here. These include poor nutrition, lack of physical activity and cigarette smoking, comorbidities or medication use. Recent work has highlighted a possible role for the early environment. Inflammaging is an exciting emerging research field that is likely to prove relevant to future work, including interventions designed to retard to reverse bone and muscle loss with age. PMID:25820482

  11. Determinants of Muscle and Bone Aging.

    PubMed

    Curtis, Elizabeth; Litwic, Anna; Cooper, Cyrus; Dennison, Elaine

    2015-11-01

    Loss of bone and muscle with advancing age represent a huge threat to loss of independence in later life. Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip, spine and distal forearm. Sarcopenia, the age related loss of muscle mass and function, may add to fracture risk by increasing falls risk. In the context of muscle aging, it is important to remember that it is not just a decline in muscle mass which contributes to the deterioration of muscle function. Other factors underpinning muscle quality come into play, including muscle composition, aerobic capacity and metabolism, fatty infiltration, insulin resistance, fibrosis and neural activation. Genetic, developmental, endocrine and lifestyle factors, such as physical activity, smoking and poor diet have dual effects on both muscle and bone mass in later life and these will be reviewed here. Recent work has highlighted a possible role for the early environment. Inflammaging is an exciting emerging research field that is likely to prove relevant to future work, including interventions designed to retard to reverse bone and muscle loss with age. PMID:25820482

  12. Aging and the Muscle-Bone Relationship

    PubMed Central

    Warren, Gordon L.; Hamrick, Mark W.

    2015-01-01

    Aging-induced declines in muscle size and quality are thought to contribute to catabolic alterations in bone, but changes in bone with age also profoundly alter its response to muscle-derived stimuli. This review provides an overview of some of the alterations that occur in muscle and bone with aging, and discusses the cellular and molecular mechanisms that may impact these age-associated changes. PMID:25559151

  13. Pathogenesis of Age-Related Bone Loss in Humans

    PubMed Central

    2013-01-01

    Background. Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. Methods. This review provides an update on mechanisms of age-related bone loss in humans based on the author’s knowledge of the field and focused literature reviews. Results. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. Conclusions. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD PMID:22923429

  14. DYSAPOPTOSIS OF OSTEOBLASTS AND OSTEOCYTES INCREASES CANCELLOUS BONE FORMATION BUT EXAGGERATES BONE POROSITY WITH AGE

    PubMed Central

    Jilka, Robert L.; O’Brien, Charles A.; Roberson, Paula K.; Bonewald, Lynda F.; Weinstein, Robert S.; Manolagas, Stavros C.

    2013-01-01

    Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in non-vertebral fractures after age 65 in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

  15. Nutritional modulators of bone remodeling during aging.

    PubMed

    Mundy, Gregory R

    2006-02-01

    Bone mass declines progressively with age in both men and women from the age of approximately 30 y. Increased longevity will inevitability be associated with an increase in the incidence of osteoporosis, its associated complications, and incurred health care costs. Current pharmacologic approaches focus on inhibiting bone resorption in those with osteoporosis but do little to improve bone mass. Increased understanding of the cellular events responsible for normal bone formation has led to multiple pathways that can be targeted to positively influence bone mass. Bone morphogenetic proteins (BMPs) have been shown to stimulate bone formation, and the BMP2 gene was recently linked to osteoporosis. BMP-2 therefore represents one potential molecular target to identify new agents to simulate bone formation. Research is accumulating on the positive effects of dietary sources that stimulate the BMP2 promoter and their effects on bone formation. Flavonoids and statins occur naturally in food products and have been shown to promote bone formation. It may be possible to influence peak bone mass by dietary means and to decrease the risk of osteoporosis in later life. To ease the future burden of osteoporosis, focusing on prevention will be key, and this could include dietary interventions to stimulate bone formation. PMID:16470007

  16. Trabecular bone score in healthy ageing

    PubMed Central

    Bazzocchi, A; Ponti, F; Diano, D; Amadori, M; Albisinni, U; Battista, G

    2015-01-01

    healthy Italian people providing age- and sex-specific reference curves for TBS. This could help clinicians to improve patient management in the detection of impaired bone mineral status and to monitor bone changes. Advances in knowledge: The study reports TBS values of a selectively enrolled Italian healthy population, ranging from younger to older ages and including males as a reference standard. Moreover, links between body composition and TBS are explored. PMID:26148778

  17. Rodent models of aging bone: an update.

    PubMed

    Syed, Farhan A; Melim, Terry

    2011-12-01

    With an increase in the average life span especially in the Western hemisphere, there is renewed interest in treating maladies of old age including osteoporosis. Age-related bone loss and resultant osteoporosis substantially increase risk of fractures and morbidity in the geriatric population leading to both a decline in the quality of life for the elderly as well as a substantial burden on the health care system. Herein, we review recent research in murine and rodent models looking at how both extrinsic and intrinsic factors such as hormones, biochemicals, neuromodulators, inflammatory cytokines, oxidative stress, nutrition, and exercise influence the skeleton with age. Recent studies on the relationship between bone and fat in the marrow, and the fate of the marrow mesenchymal stromal cell population, which can give rise to either bone-forming osteoblasts or fat-forming adipocytic cells as a function of age, have also been highlighted. An appreciable range of studies using aging murine as well as cellular models are discussed, as these studies have broadened our understanding of the pathways and players in the aging bone. Impactful information regarding aging and the bone may then allow the application of better pharmacologic as well as nonpharmacologic regimens to alleviate bone loss due to aging. PMID:21918858

  18. Healthy Bones at Every Age

    MedlinePlus

    ... include walking and running, as well as team sports like soccer and basketball. AAOS does not endorse ... to cause hormonal changes that stop menstrual periods (amenorrhea). This loss of estrogen can cause bone loss ...

  19. Role of inflammation in the aging bones.

    PubMed

    Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

    2015-02-15

    Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging. PMID:25510309

  20. [Changes in bones in the aging males].

    PubMed

    Grzegorzewska, Alicja E

    2007-08-01

    The report contains a summary of results on bone changes in aging male, presented during the 2nd CSSAM/ISAM North American Congress on the Aging Male. It was shown that age-related osteoporosis can be slowed in men by substitutive treatment with testosterone. Taking into account such therapy, one should remember about its adverse effects. PMID:18044351

  1. Bone age assessment using cephalometric photographs

    PubMed Central

    Durka-Zając, Magdalena; Marcinkowska, Agata; Mituś-Kenig, Maria

    2013-01-01

    Summary Background: The assessment of bone age comprises the basic element of orthodontic diagnostics as it enables the recognition of deviations from normal growth, determines the choice of treatment, helps determine the appropriate moment to begin treatment, establish prognosis and plan a retention strategy. In order to make an assessment of skeletal maturity possible in a single examination, radiological methods were adopted. The following characteristics are evaluated on a radiograph: the appearance, size and shape of ossification centers, the width and the shape of growth cartilage and the degree of fusion between diaphyses and epiphyses. In order to assess the maturity of bones, hand-wrist radiographs were introduced in the second decade of the 20th century. Bone age assessment of bone age could also be made based on an analysis of a morphological maturity of cervical vertebrae utilizing cephalometric radiographs. Objective: The objective of the study was to evaluate the correspondence between bone age assessments made from hand-wrist radiographs and those from cephalometric radiographs. Material/Methods: In order to fulfill the objectives, hand-wrist radiographs as well as cephalometric radiographs of 30 patients (15 girls and 15 boys) between 10 and 17 years of age were collected. Bone age of hand, wrist and cervical spine was assessed. Bone age on hand-wrist radiographs was evaluated using the Björk method, whereas cephalometric radiographs were analyzed by the Baccetti et al. method. Results: A strong and statistically highly significant (r=0.98; p<0.00001) Pearson’s correlation was found between bone age assessed from hand-wrist radiographs using Björk’s method and bone age assessed from cephalometric radiographs using the method by Baccetti et al. Conclusions: The analysis of cervical vertebrae in cephalometric radiographs appears to be the most desirable method of bone age assessment. Performing the analysis on routinely taken cephalograms

  2. The relationship between dental age, bone age and chronological age in underweight children

    PubMed Central

    Kumar, Vinod; Venkataraghavan, Karthik; Krishnan, Ramesh; Patil, Kavitha; Munoli, Karishma; Karthik, Sandhya

    2013-01-01

    Background and Objective: The knowledge of bone age and dental age is of great importance for pediatrician and pediatric dentist. It is essential for a pediatric dentist to formulate treatment plan and it is a source of complementary information for pediatrician. There are few studies, which showed the relationship between dental age, bone age and chronological age in underweight children. Therefore, objective of this study was to determine and compare dental age, bone age and chronological age in underweight children. Materials and Methods: 100 underweight children between the age group of 18-14 years were selected. Chronological age was assessed by recording date of birth. Dental age assessment was done using orthopantamogram following the method described by Demirjian. Bone age assessment was carried out using hand wrist radiograph following Bjork, Grave and Brown′s method. Results: Dental age and Bone age was delayed compared to chronological age in both sexes. The correlation between chronological age, dental age and bone age were all positive in males. Interpretation and Conclusion: The data supports the concept that dental age and bone age delay is a significant feature in underweight children. It is important to consider dental age and bone age as variables for diagnosing underweight children. To support our findings further a well-designed, controlled as well as longitudinal studies with a larger sample size is required. PMID:23946582

  3. Muscle and bone-aging and space.

    PubMed

    Rittweger, J; Gunga, H C; Felsenberg, D; Kirsch, K A

    1999-07-01

    One of the major concerns of aging, but also during and after spaceflight, is loss of muscle and bone mass. In aging, this is associated with an increasing risk of fractures. Recently, the possibility of aged and aging astronauts has been arisen. Thus considering the perspectives of aging and space we want to discuss, in how far the adaptations during spaceflight and during aging interfere. In other words: does spaceflight push the astronauts along the irreversible axis of aging? And which of the spaceflight effects will be reversible? Bones adapt to their mechanical function. For convenience, a simple model has been proposed: Bone, as a 'mechanostat', keeps the strains within certain thresholds, namely one threshold for modeling, i.e. formation of new bone, and one for remodeling, i.e. repair and removal. These thresholds are usually expressed as strains. A crucial role in physiological strain detection is obviously played by the osteocytes. The largest forces in the musculo-skeletal systems arise from muscle contractions. The reason for this are the poor levers, against which the muscles pull. For example: during a one-leg vertical jump, a young subject (body weight 70 kg) exerts a vertical ground reaction force of 2500 N. Due to the lever ratio of os calcis and forefoot around the tibio-talar joint, the calf muscles must exert a force 3 times greater, so that together with the body weight the bones of the lower leg are loaded with 10000 N, i.e. 14 times the body weight. Accordingly, good correlations can be observed between muscle strength and bone strength, or muscle mass and bone mass. It is therefore reasonable to discuss the accumulated knowledge about loss of muscle and bone in a combined approach. In this respect, two points must be considered: (i) for structural adaptation of bone, the muscular variable of interest arc force and rate of force development, but not power, and (ii) women before menopause have a greater bone to muscle ratio than men. PMID

  4. Advances in noninvasive bone measurement

    SciTech Connect

    Mazess, R.B.; Barden, H.; Vetter, J.; Ettinger, M.

    1989-01-01

    Several noninvasive measurement methods are used for evaluation of metabolic disease. Single-photon (/sup 125/I) scans of the peripheral skeleton are useful in some diseases but are ineffective in osteoporosis (even on the distal radius or os calcis) because they cannot predict spinal or femoral density. Also, peripheral measurements show high percentages of false negatives, that is many patients with fractures have normal peripheral density. Dual-photon (/sup 153/Gd) scans of the spine, femur, and total skeleton are precise and accurate (2% error) and provide direct measurements of bone strength at fracture sites. This gives the best discrimination of abnormality and the most sensitive monitoring. Quantitative computed computed tomography (QCT) allows measurement of the spine but not the critical proximal femur area. QCT has a large accuracy error because (a) the limited area measured (under 5 cm3) fails to represent the total vertebral body, (b) technical errors, and (c) variable fat and osteoid influence the results. 25 references.

  5. Fracture, aging and disease in bone

    SciTech Connect

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    From a public health perspective, developing a detailed mechanistic understanding of the well-known increase in fracture risk of human bone with age is essential. This also represents a challenge from materials science and fracture mechanics viewpoints. Bone has a complex, hierarchical structure with characteristic features ranging from nanometer to macroscopic dimensions; it is therefore significantly more complex than most engineering materials. Nevertheless, by examining the micro-/nano-structural changes accompanying the process of aging using appropriate multiscale experimental methods and relating them to fracture mechanics data, it is possible to obtain a quantitative picture of how bone resists fracture. As human cortical bone exhibits rising ex vivo crack-growth resistance with crack extension, its fracture toughness must be evaluated in terms of resistance-curve (R-curve) behavior. While the crack initiation toughness declines with age, the more striking finding is that the crack-growth toughness declines even more significantly and is essentially absent in bone from donors exceeding 85 years in age. To explain such an age-induced deterioration in the toughness of bone, we evaluate its fracture properties at multiple length scales, specifically at the molecular and nanodimensions using pico-force atomic-force microscopy, nanoindentation and vibrational spectroscopies, at the microscale using electron microscopy and hard/soft x-ray computed tomography, and at the macroscale using R-curve measurements. We show that the reduction in crack-growth toughness is associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging, and that this occurs at relatively coarse size-scales in the range of tens to hundreds of micrometers. Finally, we briefly describe how specific clinical treatments, e.g., with steroid hormones to treat various inflammatory conditions, can prematurely damage bone, thereby reducing its

  6. Age-related elemental change in bones

    NASA Astrophysics Data System (ADS)

    Wang, C.; Eisa, M. H.; Jin, W.; Shen, H.; Mi, Y.; Gao, J.; Zhou, Y.; Yao, H.; Zhao, Y.

    2008-04-01

    To investigate age dependence of the bone element contents and structure, lumbar and femur from Sprague-Dawley (SD) rats were chosen for their more susceptibility to fracture. These rats were divided into to 5 age groups: 1, 4, 7, 11 and 25 month-age, corresponding human beings from the young to the old. The elements contents were detected by external Proton Induced X-ray emission (PIXE) technique. X-ray Absorption Fine Structure (XAFS) method was also applied to obtain information about calcium (Ca) and phosphor (P) structure. It was found that Ca content, Ca/P ratio, valance state of Ca and P and their coordinate structure remains unaltered with age variance, whereas the content of strontium (Sr) was significantly decreasing. Sr concentration may provide a new parameter for diagnosis of bone disorder.

  7. Advances in cancer pain from bone metastasis

    PubMed Central

    Zhu, Xiao-Cui; Zhang, Jia-Li; Ge, Chen-Tao; Yu, Yuan-Yang; Wang, Pan; Yuan, Ti-Fei; Fu, Cai-Yun

    2015-01-01

    With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models. PMID:26316696

  8. Automated bone age assessment of older children using the radius

    NASA Astrophysics Data System (ADS)

    Tsao, Sinchai; Gertych, Arkadiusz; Zhang, Aifeng; Liu, Brent J.; Huang, Han K.

    2008-03-01

    The Digital Hand Atlas in Assessment of Skeletal Development is a large-scale Computer Aided Diagnosis (CAD) project for automating the process of grading Skeletal Development of children from 0-18 years of age. It includes a complete collection of 1,400 normal hand X-rays of children between the ages of 0-18 years of age. Bone Age Assessment is used as an index of skeletal development for detection of growth pathologies that can be related to endocrine, malnutrition and other disease types. Previous work at the Image Processing and Informatics Lab (IPILab) allowed the bone age CAD algorithm to accurately assess bone age of children from 1 to 16 (male) or 14 (female) years of age using the Phalanges as well as the Carpal Bones. At the older ages (16(male) or 14(female) -19 years of age) the Phalanges as well as the Carpal Bones are fully developed and do not provide well-defined features for accurate bone age assessment. Therefore integration of the Radius Bone as a region of interest (ROI) is greatly needed and will significantly improve the ability to accurately assess the bone age of older children. Preliminary studies show that an integrated Bone Age CAD that utilizes the Phalanges, Carpal Bones and Radius forms a robust method for automatic bone age assessment throughout the entire age range (1-19 years of age).

  9. [Sarcopenia and bone mineral property with age].

    PubMed

    Ogawa, Sumito

    2016-08-01

    In order to maintain functional activities in the elderly, promotion of musculoskeletal care is important toward successful aging and healthy longevity. In practice, reduction of falls and fall-related injuries together with treatment of osteoporosis is important to keep activities of daily living. Recent findings suggest the possibility that there is a relationship between skeletal muscle and bone mineral property, represented by pathophysiological linkage between sarcopenia and osteoporosis. PMID:27461501

  10. Bone age assessment in young children using automatic carpal bone feature extraction and support vector regression.

    PubMed

    Somkantha, Krit; Theera-Umpon, Nipon; Auephanwiriyakul, Sansanee

    2011-12-01

    Boundary extraction of carpal bone images is a critical operation of the automatic bone age assessment system, since the contrast between the bony structure and soft tissue are very poor. In this paper, we present an edge following technique for boundary extraction in carpal bone images and apply it to assess bone age in young children. Our proposed technique can detect the boundaries of carpal bones in X-ray images by using the information from the vector image model and the edge map. Feature analysis of the carpal bones can reveal the important information for bone age assessment. Five features for bone age assessment are calculated from the boundary extraction result of each carpal bone. All features are taken as input into the support vector regression (SVR) that assesses the bone age. We compare the SVR with the neural network regression (NNR). We use 180 images of carpal bone from a digital hand atlas to assess the bone age of young children from 0 to 6 years old. Leave-one-out cross validation is used for testing the efficiency of the techniques. The opinions of the skilled radiologists provided in the atlas are used as the ground truth in bone age assessment. The SVR is able to provide more accurate bone age assessment results than the NNR. The experimental results from SVR are very close to the bone age assessment by skilled radiologists. PMID:21347746

  11. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    PubMed

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  12. Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

    PubMed Central

    Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

    2012-01-01

    There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

  13. Bone health as a primary target in the pediatric age.

    PubMed

    Caradonna, P; Rigante, D

    2009-01-01

    Bone tissue is constantly renewed during childhood and adolescence to assure skeleton growth both in size and mineral density: up to 90 percent of peak bone mass is acquired by age 18 in girls and age 20 in boys, which makes youth the best time to "invest" in bone health. The reduction in bone mineral density leading to compromised strength and microarchitecture of bone tissue can favour the occurrence of fragility fractures in the pediatric age. Assessing the normality of bone density measurements in childhood by current methods is hampered by the lack of normative control data. The understanding of factors useful for maximizing peak bone mass, as well as the knowledge of diagnostic tools and therapeutic strategies for managing a state of reduced bone mineral density are crucial to prevent fractures throughout lifetime. PMID:19499847

  14. Bone age assessment for young children from newborn to 7-year-old using carpal bones

    NASA Astrophysics Data System (ADS)

    Zhang, Aifeng; Gertych, Arkadiusz; Liu, Brent J.; Huang, H. K.

    2007-03-01

    A computer-aided-diagnosis (CAD) method has been previously developed based on features extracted from phalangeal regions of interest (ROI) in a digital hand atlas, which can assess bone age of children from ages 7 to 18 accurately. Therefore, in order to assess the bone age of children in younger ages, the inclusion of carpal bones is necessary. In this paper, we developed and implemented a knowledge-based method for fully automatic carpal bone segmentation and morphological feature analysis. Fuzzy classification was then used to assess the bone age based on the selected features. Last year, we presented carpal bone segmentation algorithm. This year, research works on procedures after carpal bone segmentation including carpal bone identification, feature analysis and fuzzy system for bone age assessment is presented. This method has been successfully applied on all cases in which carpal bones have not overlapped. CAD results of total about 205 cases from the digital hand atlas were evaluated against subject chronological age as well as readings of two radiologists. It was found that the carpal ROI provides reliable information in determining the bone age for young children from newborn to 7-year-old.

  15. Research Advances in Aging 1984-1986.

    ERIC Educational Resources Information Center

    National Inst. on Aging (DHHS/NIH), Bethesda, MD.

    The National Institute on Aging (NIA) has, for the past several years, focused attention on a wide range of clinical problems associated with aging, including falls and gait disorders, bone fractures, urinary incontinence, and hypertension. Understanding the causes of and exploring possible treatments for Alzheimer's disease has been another of…

  16. Utilization of bone impedance for age estimation in postmortem cases.

    PubMed

    Ishikawa, Noboru; Suganami, Hideki; Nishida, Atsushi; Miyamori, Daisuke; Kakiuchi, Yasuhiro; Yamada, Naotake; Wook-Cheol, Kim; Kubo, Toshikazu; Ikegaya, Hiroshi

    2015-11-01

    In the field of Forensic Medicine the number of unidentified cadavers has increased due to natural disasters and international terrorism. The age estimation is very important for identification of the victims. The degree of sagittal closure is one of such age estimation methods. However it is not widely accepted as a reliable method for age estimation. In this study, we have examined whether measuring impedance value (z-values) of the sagittal suture of the skull is related to the age in men and women and discussed the possibility to use bone impedance for age estimation. Bone impedance values increased with aging and decreased after the age of 64.5. Then we compared age estimation through the conventional visual method and the proposed bone impedance measurement technique. It is suggested that the bone impedance measuring technique may be of value to forensic science as a method of age estimation. PMID:26421720

  17. En bloc resection of the temporal bone and temporomandibular joint for advanced temporal bone carcinoma.

    PubMed

    Kutz, Joe Walter; Mitchell, Derek; Isaacson, Brandon; Roland, Peter S; Allen, Kyle P; Sumer, Baran D; Barnett, Sam; Truelson, John M; Myers, Larry L

    2015-03-01

    Advanced skin malignancies involving the temporal bone can involve the temporomandibular joint and glenoid fossa. Many of these tumors can be removed with a lateral temporal bone resection; however, extensive involvement of the glenoid fossa should include an en bloc resection of the temporal bone, glenoid fossa, and condyle. We describe a novel surgical approach that is an extension of a temporal bone resection that includes the glenoid fossa and condyle in an en bloc resection with the temporal bone. This procedure has been performed in 7 patients with advanced carcinoma of the temporal bone involving the glenoid fossa. There were no short-term complications as a result of the surgical approach. The addition of a middle fossa craniotomy and inclusion of the glenoid fossa and condyle as part of an en bloc resection of the temporal bone can be performed safely. PMID:25616770

  18. Recent advances in bone regeneration using adult stem cells.

    PubMed

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration. PMID:25914769

  19. Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

    NASA Technical Reports Server (NTRS)

    Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

    1996-01-01

    Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

  20. Hyoid bone fusion and bone density across the lifespan: prediction of age and sex.

    PubMed

    Fisher, Ellie; Austin, Diane; Werner, Helen M; Chuang, Ying Ji; Bersu, Edward; Vorperian, Houri K

    2016-06-01

    The hyoid bone supports the important functions of swallowing and speech. At birth, the hyoid bone consists of a central body and pairs of right and left lesser and greater cornua. Fusion of the greater cornua with the body normally occurs in adulthood, but may not occur at all in some individuals. The aim of this study was to quantify hyoid bone fusion across the lifespan, as well as assess developmental changes in hyoid bone density. Using a computed tomography imaging studies database, 136 hyoid bones (66 male, 70 female, ages 1-to-94) were examined. Fusion was ranked on each side and hyoid bones were classified into one of four fusion categories based on their bilateral ranks: bilateral distant non-fusion, bilateral non-fusion, partial or unilateral fusion, and bilateral fusion. Three-dimensional hyoid bone models were created and used to calculate bone density in Hounsfield units. Results showed a wide range of variability in the timing and degree of hyoid bone fusion, with a trend for bilateral non-fusion to decrease after age 20. Hyoid bone density was significantly lower in adult female scans than adult male scans and decreased with age in adulthood. In sex and age estimation models, bone density was a significant predictor of sex. Both fusion category and bone density were significant predictors of age group for adult females. This study provides a developmental baseline for understanding hyoid bone fusion and bone density in typically developing individuals. Findings have implications for the disciplines of forensics, anatomy, speech pathology, and anthropology. PMID:27114259

  1. Aging bone in men and women: beyond changes in bone mineral density.

    PubMed

    Russo, C R; Lauretani, F; Bandinelli, S; Bartali, B; Di Iorio, A; Volpato, S; Guralnik, J M; Harris, T; Ferrucci, L

    2003-07-01

    Using peripheral quantitative computed tomography (pQCT) we assessed trabecular and cortical bone density, mass and geometric distribution at the tibia level in 512 men and 693 women, age range 20-102 years, randomly selected from the population living in the Chianti area, Tuscany, Italy. Total, trabecular and cortical bone density decreased linearly with age ( p<0.0001 in both sexes), and the slope of age-associated decline was steeper in women than in men. In men, the cortical bone area was similar in different age groups, while in women older than 60 years it was significantly smaller by approximately 1% per year. The total cross-sectional area of the bone became progressively wider with age, but the magnitude of the age-associated increment was significantly higher in men than in women ( p<0.001). The minimum moment of inertia, an index of mechanical resistance to bending, remained stable with age in men, while it was significantly lower in older compared with younger women (0.5% per year). The increase in bone cross-sectional area in aging men may contribute to the maintenance of adequate bone mechanical competence in the face of declining bone density. In women this compensatory mechanism appears to be less efficient and, accordingly, the bone mechanical competence declines with age. The geometric adaptation of increasing cross-sectional bone size is an important component in the assessment of bone mechanical resistance which is completely overlooked, and potentially misinterpreted, by traditional planar densitometry. PMID:12827220

  2. Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

    2002-01-01

    The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

  3. Aging changes in the bones - muscles - joints

    MedlinePlus

    ... the skin and hair are also common. The skeleton provides support and structure to the body. Joints ... areas where bones come together. They allow the skeleton to be flexible for movement. In a joint, ...

  4. Age at death estimation from bone histology in Malaysian males.

    PubMed

    Nor, Faridah Mohd; Pastor, Robert F; Schutkowski, Holger

    2014-10-01

    Estimation of age from microscopic examination of human bone utilizes bone remodeling. This allows 2 regression equation to be determined in a specific population based on the variation in osteon turnover in different populations. The aim of this study was to provide age estimation for Malaysian males. Ground undecalcified cross sections were prepared from long limb bones of 50 deceased males aged between 21 and 78 years. Ten microstructural parameters were measured and subjected to multivariate regression analysis. Results showed that osteon count had the highest correlation with age (R = 0.43), and age was estimated to be within 10.94 years of the true value in 98% of males. Cross validation of the equation on 50 individuals showed close correspondence of true ages with estimated ages. Further studies are needed to validate and expand these results. PMID:24189643

  5. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells.

    PubMed

    Li, Ziqing; Li, Chaohong; Zhou, Yuhuan; Chen, Weishen; Luo, Guotian; Zhang, Ziji; Wang, Haixing; Zhang, Yangchun; Xu, Dongliang; Sheng, Puyi

    2016-03-01

    Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW264.7 cell-derived osteoclast-like cells (OCLs). AGE-modified BSA (50-400 μg/ml) or control BSA (100 μg/ml) was then added at the beginning of each stage. Results showed that the presence of AGEs at the cell fusion stage reduced pit numbers, resorption area, and CTSK expression. Moreover, expression of receptor activator of nuclear factor-κB (RANK) as well as the number of TRAP-positive cells, nuclei per OCL, actin rings, and podosomes also decreased. However, the presence of AGEs at the mature stage enlarged the resorption area markedly and increased pit numbers slightly. Intriguingly, only the number of nuclei per OCL and podosomes increased. These data indicate that AGEs biphasically modulate bone resorption activity of OCLs in a differentiation stage-dependent manner. AGEs at the cell fusion stage reduce bone resorption dramatically, mainly via suppression of RANK expression in osteoclast precursors, whereas AGEs at the mature stage enhance bone resorption slightly, most likely by increasing the number of podosomes in mature OCLs. PMID:26670486

  6. IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

    PubMed

    Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

    2016-02-01

    Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data

  7. Advanced Ultrasonic Tomograph of Children's Bones

    NASA Astrophysics Data System (ADS)

    Lasaygues, Philippe; Lefebvre, Jean-Pierre; Guillermin, Régine; Kaftandjian, Valérie; Berteau, Jean-Philippe; Pithioux, Martine; Petit, Philippe

    This study deals with the development of an experimental device for performing ultrasonic computed tomography (UCT) on bone in pediatric degrees. The children's bone tomographs obtained in this study, were based on the use of a multiplexed 2-D ring antenna (1 MHz and 3 MHz) designed for performing electronic and mechanical scanning. Although this approach is known to be a potentially valuable means of imaging objects with similar acoustical impedances, problems arise when quantitative images of more highly contrasted media such as bones are required. Various strategies and various mathematical procedures for modeling the wave propagation based on Born approximations have been developed at our laboratory, which are suitable for use with pediatric cases. Inversions of the experimental data obtained are presented.

  8. Aging changes in the bones - muscles - joints

    MedlinePlus

    Osteoporosis and aging; Muscle weakness associated with aging; Osteoarthritis ... ranging from mild stiffness to debilitating arthritis (see osteoarthritis ) are very common. The risk of injury increases ...

  9. [Psychosocial rehabilitation in advanced age].

    PubMed

    Haag, G

    1985-02-01

    The psychosocial rehabilitation of older persons is one of the main problems in health policy. About one quarter of the over 65-year-olds face psychic problems, without, to a large extent, receiving adequate treatment and rehabilitative care. Substantial deficits exist above all in the out-patient and non-residential service sectors. In in-patient care, existing methods for psychosocial intervention (such as psychoanalysis, behavioural, client-centered, family, Gestalt, milieu, or music and dance therapy, psychodrama, reality orientation training, or resensitization techniques) are hardly ever used. This absence of applied geronto-psychology is attributable to the shortcomings of available assessment methods, multiple methodical problems of intervention research, and--above all--to insufficient staff positions for psychosocial professions in the gerontological sector. Provision of further permanent posts for psychosocial workers; development of age-specific assessment methods; interdisciplinary and systematic interventional research; the development of ambulatory, community-based services as well as intensive support for existing self-help efforts are therefore called for. PMID:3983463

  10. Bone age maturity assessment using hand-held device

    NASA Astrophysics Data System (ADS)

    Ratib, Osman M.; Gilsanz, Vicente; Liu, Xiaodong; Boechat, M. I.

    2004-04-01

    Purpose: Assessment of bone maturity is traditionally performed through visual comparison of hand and wrist radiograph with existing reference images in textbooks. Our goal was to develop a digital index based on idealized hand Xray images that can be incorporated in a hand held computer and used for visual assessment of bone age for patients. Material and methods: Due to the large variability in bone maturation in normals, we generated a set of "ideal" images obtained by computer combinations of images from our normal reference data sets. Software for hand-held PDA devices was developed for easy navigation through the set of images and visual selection of matching images. A formula based on our statistical analysis provides the standard deviation from normal based on the chronological age of the patient. The accuracy of the program was compared to traditional interpretation by two radiologists in a double blind reading of 200 normal Caucasian children (100 boys, 100 girls). Results: Strong correlations were present between chronological age and bone age (r > 0.9) with no statistical difference between the digital and traditional assessment methods. Determinations of carpal bone maturity in adolescents was slightly more accurate using the digital system. The users did praise the convenience and effectiveness of the digital Palm Index in clinical practice. Conclusion: An idealized digital Palm Bone Age Index provides a convenient and effective alternative to conventional atlases for the assessment of skeletal maturity.

  11. Age-related changes in mouse bone permeability.

    PubMed

    Rodriguez-Florez, Naiara; Oyen, Michelle L; Shefelbine, Sandra J

    2014-03-21

    The determination of lacunar-canalicular permeability is essential for understanding local fluid flow in bone, which may indicate how bone senses changes in the mechanical environment to regulate mechano-adaptation. The estimates of lacunar-canalicular permeability found in the literature vary by up to eight orders of magnitude, and age-related permeability changes have not been measured in non-osteonal mouse bone. The objective of this study is to use a poroelastic approach based on nanoindentation data to characterize lacunar-canalicular permeability in murine bone as a function of age. Nine wild type C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from each age group were embedded in epoxy resin, cut in half and indented in the longitudinal direction in the mid-cortex using two spherical fluid indenter tips (R=238 μm and 500 μm). Results suggest that the lacunar-canalicular intrinsic permeability of mouse bone decreases from 2 to 7 months, with no significant changes from 7 to 12 months. The large indenter tip imposed larger contact sizes and sampled larger ranges of permeabilities, particularly for the old bone. This age-related difference in the distribution was not seen for indents with the smaller radius tip. We conclude that the small tip effectively measured lacunar-canalicular permeability, while larger tip indents were influenced by vascular permeability. Exploring the age-related changes in permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. This understanding may help indicate alterations in bone adaptation and remodeling. PMID:24433671

  12. Current methods and advances in bone densitometry

    NASA Technical Reports Server (NTRS)

    Guglielmi, G.; Gluer, C. C.; Majumdar, S.; Blunt, B. A.; Genant, H. K.

    1995-01-01

    Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis.

  13. Current methods and advances in bone densitometry.

    PubMed

    Guglielmi, G; Gluer, C C; Majumdar, S; Blunt, B A; Genant, H K

    1995-01-01

    Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis. PMID:11539928

  14. Age dependence of natural uranium and thorium concentrations in bone.

    PubMed

    Larivière, Dominic; Packer, Ana Paula; Marro, Leonora; Li, Chunsheng; Chen, Jing; Cornett, R Jack

    2007-02-01

    The age dependence of the natural concentration of uranium and thorium in the skeleton was investigated using human vertebrae bone collected from two Canadian locations (Winnipeg, Manitoba, and Regina, Saskatchewan). The concentration of both radioelements in digested ashed bone samples was determined using sector-field inductively coupled plasma mass spectrometry. The geometric means for uranium level in bones showed a significant statistical difference between the two locations studied. Similarly for thorium, a statistical difference was observed, although this difference was considered marginal. The thorium concentration differed only marginally with respect to age group, indicating that its behavior in the body could be age-independent. Conversely, the uranium level in bones was found to change for the age groups tested, an indication of age-specific deposition. The age profile for uranium was comparable to the calcium turn-over rate, indicating that uranium deposition is probably, in part, dictated by this metabolic process, showing the role of present uptake into the uranium concentration in bones for populations exposed to significant uranium intake. PMID:17220713

  15. Radiological Indicators of Bone Age Assessment in Cephalometric Images. Review

    PubMed Central

    Durka-Zając, Magdalena; Mituś-Kenig, Maria; Derwich, Marcin; Marcinkowska-Mituś, Agata; Łoboda, Magdalena

    2016-01-01

    Summary The ability to assess bone age accurately is important and allows to diagnose the patient correctly and to plan orthodontic treatment appropriately. The aim of the work is to present views of different authors on the subject of using cephalometric images to determine bone age and its significance for conducting appropriate orthodontic treatment. Publications from the PubMed medical database were analyzed. Search criteria: bone age assessment, CVM method. Ultimately, 36 papers out of 1354 publications were selected. The research of many authors confirms the usefulness of various methods using cephalometric images to assess skeletal age. Currently, the CVM method devised by Baccetti et al. is the most frequently mentioned one in literature. It seems that bone age assessment methods based on evaluating the morphological structure of the cervical vertebrae in cephalometric images can clearly differentiate skeletal maturity in children regardless of their race or sex. Bearing in mind the constant technological progress in medicine and stomatology, bone age assessment methods need to be perfected in order to alleviate their impact on the patient as much as possible. PMID:27536337

  16. Radiological Indicators of Bone Age Assessment in Cephalometric Images. Review.

    PubMed

    Durka-Zając, Magdalena; Mituś-Kenig, Maria; Derwich, Marcin; Marcinkowska-Mituś, Agata; Łoboda, Magdalena

    2016-01-01

    The ability to assess bone age accurately is important and allows to diagnose the patient correctly and to plan orthodontic treatment appropriately. The aim of the work is to present views of different authors on the subject of using cephalometric images to determine bone age and its significance for conducting appropriate orthodontic treatment. Publications from the PubMed medical database were analyzed. Search criteria: bone age assessment, CVM method. Ultimately, 36 papers out of 1354 publications were selected. The research of many authors confirms the usefulness of various methods using cephalometric images to assess skeletal age. Currently, the CVM method devised by Baccetti et al. is the most frequently mentioned one in literature. It seems that bone age assessment methods based on evaluating the morphological structure of the cervical vertebrae in cephalometric images can clearly differentiate skeletal maturity in children regardless of their race or sex. Bearing in mind the constant technological progress in medicine and stomatology, bone age assessment methods need to be perfected in order to alleviate their impact on the patient as much as possible. PMID:27536337

  17. Structural basis of growth-related gain and age-related loss of bone strength

    PubMed Central

    2008-01-01

    If bone strength was the only requirement of skeleton, it could be achieved with bulk, but bone must also be light. During growth, bone modelling and remodelling optimize strength, by depositing bone where it is needed, and minimize mass, by removing it from where it is not. The population variance in bone traits is established before puberty and the position of an individual's bone size and mass tracks in the percentile of origin. Larger cross-sections have a comparably larger marrow cavity, which results in a lower volumetric BMD (vBMD), thereby avoiding bulk. Excavation of a marrow cavity thus minimizes mass and shifts the cortex radially, increasing rigidity. Smaller cross-sections are assembled by excavating a smaller marrow cavity leaving a relatively thicker cortex producing a higher vBMD, avoiding the fragility of slenderness. Variation in cellular activity around the periosteal and endocortical envelopes fashions the diverse shapes of adjacent cross-sections. Advancing age is associated with a decline in periosteal bone formation, a decline in the volume of bone formed by each basic multicellular unit (BMU), continued resorption by each BMU, and high remodelling after menopause. Bone loss in young adulthood has modest structural and biomechanical consequences because the negative BMU balance is driven by reduced bone formation, remodelling is slow and periosteal apposition continues shifting the thinned cortex radially. But after the menopause, increased remodelling, worsening negative BMU balance and a decline in periosteal apposition accelerate cortical thinning and porosity, trabecular thinning and loss of connectivity. Interstitial bone, unexposed to surface remodelling becomes more densely mineralized, has few osteocytes and greater collagen cross-linking, and accumulates microdamage. These changes produce the material and structural abnormalities responsible for bone fragility. PMID:18556646

  18. Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone.

    PubMed

    Todd, Henry; Galea, Gabriel L; Meakin, Lee B; Delisser, Peter J; Lanyon, Lance E; Windahl, Sara H; Price, Joanna S

    2015-01-01

    Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to

  19. Segmentation of bone pixels from EROI Image using clustering method for bone age assessment

    NASA Astrophysics Data System (ADS)

    Bakthula, Rajitha; Agarwal, Suneeta

    2016-03-01

    The bone age of a human can be identified using carpal and epiphysis bones ossification, which is limited to teen age. The accurate age estimation depends on best separation of bone pixels and soft tissue pixels in the ROI image. The traditional approaches like canny, sobel, clustering, region growing and watershed can be applied, but these methods requires proper pre-processing and accurate initial seed point estimation to provide accurate results. Therefore this paper proposes new approach to segment the bone from soft tissue and background pixels. First pixels are enhanced using BPE and the edges are identified by HIPI. Later a K-Means clustering is applied for segmentation. The performance of the proposed approach has been evaluated and compared with the existing methods.

  20. Advancing Paternal Age and Simplex Autism

    ERIC Educational Resources Information Center

    Puleo, Connor Morrow; Schmeidler, James; Reichenberg, Abraham; Kolevzon, Alexander; Soorya, Latha V.; Buxbaum, Joseph D.; Silverman, Jeremy M.

    2012-01-01

    De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling…

  1. Content-based image retrieval applied to bone age assessment

    NASA Astrophysics Data System (ADS)

    Fischer, Benedikt; Brosig, André; Welter, Petra; Grouls, Christoph; Günther, Rolf W.; Deserno, Thomas M.

    2010-03-01

    Radiological bone age assessment is based on local image regions of interest (ROI), such as the epiphysis or the area of carpal bones. These are compared to a standardized reference and scores determining the skeletal maturity are calculated. For computer-aided diagnosis, automatic ROI extraction and analysis is done so far mainly by heuristic approaches. Due to high variations in the imaged biological material and differences in age, gender and ethnic origin, automatic analysis is difficult and frequently requires manual interactions. On the contrary, epiphyseal regions (eROIs) can be compared to previous cases with known age by content-based image retrieval (CBIR). This requires a sufficient number of cases with reliable positioning of the eROI centers. In this first approach to bone age assessment by CBIR, we conduct leaving-oneout experiments on 1,102 left hand radiographs and 15,428 metacarpal and phalangeal eROIs from the USC hand atlas. The similarity of the eROIs is assessed by cross-correlation of 16x16 scaled eROIs. The effects of the number of eROIs, two age computation methods as well as the number of considered CBIR references are analyzed. The best results yield an error rate of 1.16 years and a standard deviation of 0.85 years. As the appearance of the hand varies naturally by up to two years, these results clearly demonstrate the applicability of the CBIR approach for bone age estimation.

  2. Aging of microstructural compartments in human compact bone

    NASA Technical Reports Server (NTRS)

    Akkus, Ozan; Polyakova-Akkus, Anna; Adar, Fran; Schaffler, Mitchell B.

    2003-01-01

    Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the

  3. Bioactive Silica Nanoparticles Reverse Age-Associated Bone Loss in Mice

    PubMed Central

    Vikulina, Tatyana; Roser-Page, Susanne; Lee, Jin-Kyu; Beck, George R.

    2015-01-01

    We recently reported that in vitro, engineered 50 nm spherical silica nanoparticles promote the differentiation and activity of bone building osteoblasts but suppress that of bone-resorbing osteoclasts. Furthermore, these nanoparticles promote bone accretion in young mice in vivo. In the present study the capacity of these nanoparticles to reverse bone loss in aged mice, a model of human senile osteoporosis, was investigated. Aged mice received nanoparticles weekly and bone mineral density (BMD), bone structure, and bone turnover was quantified. Our data revealed a significant increase in BMD, bone volume, and biochemical markers of bone formation. Biochemical and histological examinations failed to identify any abnormalities caused by nanoparticle administration. Our studies demonstrate that silica nanoparticles effectively blunt and reverse age-associated bone loss in mice by a mechanism involving promotion of bone formation. The data suggest that osteogenic silica nanoparticles may be a safe and effective therapeutic for counteracting age-associated bone loss. PMID:25680544

  4. Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice.

    PubMed

    Rubin, Mishaela R; Paschalis, Eleftherios P; Poundarik, Atharva; Sroga, Gyna E; McMahon, Donald J; Gamsjaeger, Sonja; Klaushofer, Klaus; Vashishth, Deepak

    2016-01-01

    Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices. PMID:27140650

  5. Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice

    PubMed Central

    Rubin, Mishaela R.; Paschalis, Eleftherios P.; Poundarik, Atharva; Sroga, Gyna E.; McMahon, Donald J.; Gamsjaeger, Sonja; Klaushofer, Klaus; Vashishth, Deepak

    2016-01-01

    Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices. PMID:27140650

  6. The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone.

    PubMed

    Tang, S Y; Vashishth, D

    2011-01-11

    The risk of fracture increases with age due to the decline of bone mass and bone quality. One of the age-related changes in bone quality occurs through the formation and accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation (NEG). However as a number of other changes including increased porosity occur with age and affect bone fragility, the relative contribution of AGEs on the fracture resistance of aging bone is unknown. Using a high-resolution nonlinear finite element model that incorporate cohesive elements and micro-computed tomography-based 3d meshes, we investigated the contribution of AGEs and cortical porosity on the fracture toughness of human bone. The results show that NEG caused a 52% reduction in propagation fracture toughness (R-curve slope). The combined effects of porosity and AGEs resulted in an 88% reduction in propagation toughness. These findings are consistent with previous experimental results. The model captured the age-related changes in the R-curve toughening by incorporating bone quantity and bone quality changes, and these simulations demonstrate the ability of the cohesive models to account for the irreversible dynamic crack growth processes affected by the changes in post-yield material behavior. By decoupling the matrix-level effects due to NEG and intracortical porosity, we are able to directly determine the effects of NEG on fracture toughness. The outcome of this study suggests that it may be important to include the age-related changes in the material level properties by using finite element analysis towards the prediction of fracture risk. PMID:21056419

  7. Diagnostic workstation for digital hand atlas in bone age assessment

    NASA Astrophysics Data System (ADS)

    Cao, Fei; Huang, H. K.; Pietka, Ewa; Gilsanz, Vicente; Ominsky, Steven

    1998-06-01

    Bone age assessment by a radiological examination of a hand and wrist image is a procedure frequently performed in pediatric patients to evaluate growth disorders, determine growth potential in children and monitor therapy effects. The assessment method currently used in radiological diagnosis is based on atlas matching of the diagnosed hand image with the reference set of atlas patterns, which was developed in 1950s and is not fully applicable for children of today. We intent to implement a diagnostic workstation for creating a new reference set of clinically normal images which will serve as a digital atlas and can be used for a computer-assisted bone age assessment. In this paper, we present the initial data- collection and system setup phase of this five-year research program. We describe the system design, user interface implementation and software tool development for collection, visualization, management and processing of clinically normal hand and wrist images.

  8. Exercise in youth: High bone mass, large bone size, and low fracture risk in old age.

    PubMed

    Tveit, M; Rosengren, B E; Nilsson, J Å; Karlsson, M K

    2015-08-01

    Physical activity is favorable for peak bone mass but if the skeletal benefits remain and influence fracture risk in old age is debated. In a cross-sectional controlled mixed model design, we compared dual X-ray absorptiometry-derived bone mineral density (BMD) and bone size in 193 active and retired male elite soccer players and 280 controls, with duplicate measurements of the same individual done a mean 5 years apart. To evaluate lifetime fractures, we used a retrospective controlled study design in 397 retired male elite soccer players and 1368 controls. Differences in bone traits were evaluated by Student's t-test and fracture risk assessments by Poisson regression and Cox regression. More than 30 years after retirement from sports, the soccer players had a Z-score for total body BMD of 0.4 (0.1 to 0.6), leg BMD of 0.5 (0.2 to 0.8), and femoral neck area of 0.3 (0.0 to 0.5). The rate ratio for fracture after career end was 0.6 (0.4 to 0.9) and for any fragility fracture 0.4 (0.2 to 0.9). Exercise-associated bone trait benefits are found long term after retirement from sports together with a lower fracture risk. This indicates that physical activity in youth could reduce the burden of fragility fractures. PMID:25109568

  9. Greater Bone Formation Induction Occurred in Aged than Young Cancellous Bone Sites

    NASA Technical Reports Server (NTRS)

    Ke, H. Z.; Jee, W. S. S.; Ito, H.; Setterberg, R. B.; Li, M.; Lin, B. Y.; Liang, X. G.; Ma, Y. F.

    1993-01-01

    We have determined the differences in the effects of continual prostaglandin E(sub 2) (PGE(sub 2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE(sub 2)/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE(sub 2)/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE(sub 2) treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE(sub 2) treatment than young growing metaphysis.

  10. Automated Bone Age Assessment: Motivation, Taxonomies, and Challenges

    PubMed Central

    Ismail, Maizatul Akmar; Herawan, Tutut; Gopal Raj, Ram; Abdul Kareem, Sameem; Nasaruddin, Fariza Hanum

    2013-01-01

    Bone age assessment (BAA) of unknown people is one of the most important topics in clinical procedure for evaluation of biological maturity of children. BAA is performed usually by comparing an X-ray of left hand wrist with an atlas of known sample bones. Recently, BAA has gained remarkable ground from academia and medicine. Manual methods of BAA are time-consuming and prone to observer variability. This is a motivation for developing automated methods of BAA. However, there is considerable research on the automated assessment, much of which are still in the experimental stage. This survey provides taxonomy of automated BAA approaches and discusses the challenges. Finally, we present suggestions for future research. PMID:24454534

  11. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  12. Nanoparticulate drug delivery platforms for advancing bone infection therapies

    PubMed Central

    Uskoković, Vuk; Desai, Tejal A

    2015-01-01

    Introduction The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition. Areas covered Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is compensated for by the strength of its complement and an ideal bone substitute should be fundamentally the same. Expert opinion Discrepancy between in vitro and in vivo bioactivity assessments is highlighted, alongside the inherent imperfectness of the former. Challenges entailing the cross-disciplinary nature of engineering a new generation of drug delivery vehicles are delineated and it is concluded that the future for the nanoparticulate therapeutic carriers belongs to multifunctional, synergistic and theranostic composites capable of simultaneously targeting, monitoring and treating internal organismic disturbances in a smart, feedback fashion and in direct response to the demands of the local environment. PMID:25109804

  13. Overconstrained library-based fitting method reveals age- and disease-related differences in transcutaneous Raman spectra of murine bones

    PubMed Central

    Maher, Jason R.; Inzana, Jason A.; Awad, Hani A.; Berger, Andrew J.

    2013-01-01

    Abstract. Clinical diagnoses of bone health and fracture risk typically rely on measurements of bone density or structure, but the strength of a bone is also dependent on its chemical composition. Raman spectroscopy has been used extensively in ex vivo studies to measure the chemical composition of bone. Recently, spatially offset Raman spectroscopy (SORS) has been utilized to measure bone transcutaneously. Although the results are promising, further advancements are necessary to make noninvasive, in vivo measurements of bone with SORS that are of sufficient quality to generate accurate predictions of fracture risk. In order to separate the signals from bone and soft tissue that contribute to a transcutaneous measurement, we developed an overconstrained extraction algorithm that is based on fitting with spectral libraries. This approach allows for accurate spectral unmixing despite the fact that similar chemical components (e.g., type I collagen) are present in both bone and soft tissue. The algorithm was utilized to transcutaneously detect biochemical differences in the tibiae of wild-type mice between 1 and 7 months of age and between the tibiae of wild-type mice and a mouse model of osteogenesis imperfecta. These results represent the first diagnostically sensitive, transcutaneous measurements of bone using SORS. PMID:23817761

  14. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    SciTech Connect

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  15. Using the gradient of human cortical bone properties to determine age-related bone changes via ultrasonic guided waves.

    PubMed

    Baron, Cécile

    2012-06-01

    Bone fragility depends not only on bone mass but also on bone quality (structure and material). To accurately evaluate fracture risk or propose therapeutic treatment, clinicians need a criterion, which reflects the determinants of bone strength: geometry, structure and material. In human long bone, the changes due to aging, accentuated by osteoporosis are often revealed through the trabecularization of cortical bone, i.e., increased porosity of endosteal bone inducing a thinning of the cortex. Consequently, the intracortical porosity gradient corresponding to the spatial variation in porosity across the cortical thickness is representative of loss of mass, changes in geometry (thinning) and variations in structure (porosity). This article examines the gradient of material properties and its age-related evolution as a relevant parameter to assess bone geometry, structure and material. By applying a homogenization process, cortical bone can be considered as an anisotropic functionally graded material with variations in material properties. A semi-analytical method based on the sextic Stroh formalism is proposed to solve the wave equation in an anisotropic functionally graded waveguide for two geometries, a plate and a tube, without using a multilayered model to represent the structure. This method provides an analytical solution called the matricant and explicitly expressed under the Peano series expansion form. Our findings indicate that ultrasonic guided waves are sensitive to the age-related evolution of realistic gradients in human bone properties across the cortical thickness and have their place in a multimodal clinical protocol. PMID:22502890

  16. Male biological clock: a critical analysis of advanced paternal age

    PubMed Central

    Ramasamy, Ranjith; Chiba, Koji; Butler, Peter; Lamb, Dolores J.

    2016-01-01

    Extensive research defines the impact of advanced maternal age on couples’ fecundity and reproductive outcomes, but significantly less research has been focused on understanding the impact of advanced paternal age. Yet it is increasingly common for couples at advanced ages to conceive children. Limited research suggests that the importance of paternal age is significantly less than that of maternal age, but advanced age of the father is implicated in a variety of conditions affecting the offspring. This review examines three aspects of advanced paternal age: the potential problems with conception and pregnancy that couples with advanced paternal age may encounter, the concept of discussing a limit to paternal age in a clinical setting, and the risks of diseases associated with advanced paternal age. As paternal age increases, it presents no absolute barrier to conception, but it does present greater risks and complications. The current body of knowledge does not justify dissuading older men from trying to initiate a pregnancy, but the medical community must do a better job of communicating to couples the current understanding of the risks of conception with advanced paternal age. PMID:25881878

  17. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

    PubMed Central

    Fan, Ruoxun; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  18. Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation.

    PubMed

    Fan, Ruoxun; Gong, He; Zhang, Xianbin; Liu, Jun; Jia, Zhengbin; Zhu, Dong

    2016-01-01

    The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone. PMID:27403206

  19. The Associations of Serum Serotonin with Bone Traits Are Age- and Gender-Specific

    PubMed Central

    Wang, Qin; Chen, Decai; Nicholson, Patrick; Cheng, Shumei; Alen, Markku; Mao, Lijian; Cheng, Sulin

    2014-01-01

    Context Serotonin plays a potential role in bone metabolism, but the nature and extent of this relationship is unclear and human studies directly addressing the skeletal effect of circulating serotonin are rare. Objective The study aimed to investigate the associations between serum serotonin and bone traits at multiple skeletal sites in women and men. Subjects and Methods Subjects were part of the CALEX-family study and comprised 235 young women, 121 premenopausal women, 124 postmenopausal women, and 168 men. Body composition was assessed using DXA, as was areal bone mineral density (aBMD) of spine, femur and whole body. In addition, pQCT was used to determine bone properties at tibial midshaft and distal radius. Fasting serum serotonin concentration was assessed using a competitive enzyme-linked immunosorbent assay. Results Serum serotonin declined with advancing age both in females and males (all p<0.01). Serotonin was negatively correlated with weight, BMI, lean and fat mass in women (r = −0.22 to −0.39, all p<0.001), but positively with height and lean mass in men (all p<0.01). In the premenopausal women, serotonin was negatively correlated with lumbar spine aBMD (r = −0.23, p<0.05) but the statistical significance disappeared after adjustment for weight. Conversely, in postmenopausal women, serotonin was positively correlated with whole body and femur aBMD, as well as with distal radius bone mineral content and volumetric BMD (r = 0.20 to 0.30, all p<0.05), and these associations remained significant after adjustment for weight. In men, no significant associations were found between serotonin and bone traits. Conclusion Serum serotonin is positively associated with bone traits in postmenopausal women, but not in premenopausal women or men. This partially supports the idea of circulating serotonin playing a role in the regulation of bone metabolism, but also indicates the importance of gender and age specific factors. PMID:25279460

  20. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    PubMed

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities. PMID:26750746

  1. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... than skulls or vertebral column bones of cattle 30 months of age and older as provided in § 310.22 of... or bone marrow as measured by the presence of calcium and iron in excess of the requirements in this... nearest 10th, is more than 130.0 mg per 100 g. (ii) Bone marrow. The product's added iron...

  2. Effect of in vivo loading on bone composition varies with animal age

    PubMed Central

    Aido, Marta; Kerschnitzki, Michael; Hoerth, Rebecca; Checa, Sara; Spevak, Lyudmila; Boskey, Adele; Fratzl, Peter; Duda, Georg N.; Wagermaier, Wolfgang; Willie, Bettina M.

    2015-01-01

    Loading can increase bone mass and size and this response is reduced with aging. It is unclear, however how loading affects bone mineral and matrix properties. Fourier Transform Infrared Imaging and high resolution synchrotron scanning small angle X-ray scattering were used to study how bone’s microscale and nanoscale compositional properties were altered in the tibial midshaft of young, adult, and elderly female C57Bl/6J mice after two weeks of controlled in vivo compressive loading in comparison to physiological loading. The effect of controlled loading on bone composition varied with animal age, since it predominantly influenced the bone composition of elderly mice. Interestingly, controlled loading led to enhanced collagen maturity in elderly mice. In addition, although the rate of bone formation was increased by controlled loading based on histomorphometry, the newly formed tissue had similar material quality to new bone tissue formed during physiological loading. Similar to previous studies, our data showed that bone composition was animal and tissue age dependent during physiological loading. The findings that the new tissue formed in response to controlled loading and physiological loading had similar bone composition and that controlled loading enhanced bone composition in elderly mice further supports the use of physical activity as a noninvasive treatment to enhance bone quality as well as maintain bone mass in individuals suffering from age-related bone loss. PMID:25639943

  3. DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism

    PubMed Central

    Chen, Qian; Liu, Kai; Robinson, Andria R.; Clauson, Cheryl L.; Blair, Harry C.; Robbins, Paul D.; Niedernhofer, Laura J.; Ouyang, Hongjiao

    2013-01-01

    Advanced age is one of the most important risk factors for osteoporosis. Accumulation of oxidative DNA damage has been proposed to contribute to age-related deregulation of osteoblastic and osteoclastic cells. ERCC1 (Excision Repair Cross Complementary group 1)-XPF (Xeroderma Pigmentosum Group F) is an evolutionarily conserved structure-specific endonuclease that is required for multiple DNA repair pathways. Inherited mutations affecting expression of ERCC1-XPF cause a severe progeroid syndrome in humans, including early onset of osteopenia and osteoporosis, or anomalies in skeletal development. Herein, we used progeroid ERCC1-XPF deficient mice, including Ercc1-null (Ercc1−/−) and hypomorphic (Ercc1−/Δ) mice, to investigate the mechanism by which DNA damage leads to accelerated bone aging. Compared to their wild-type littermates, both Ercc1−/− and Ercc1−/Δ mice display severe, progressive osteoporosis caused by reduced bone formation and enhanced osteoclastogenesis. ERCC1 deficiency leads to atrophy of osteoblastic progenitors in the bone marrow stromal cell (BMSC) population. There is increased cellular senescence of BMSCs and osteoblastic cells, as characterized by reduced proliferation, accumulation of DNA damage and a senescence-associated secretory phenotype (SASP). This leads to enhanced secretion of inflammatory cytokines known to drive osteoclastogenesis, such as IL-6, TNFα, and RANKL and thereby induces an inflammatory bone microenvironment favoring osteoclastogenesis. Furthermore, we found that the transcription factor NF-κB is activated in osteoblastic and osteoclastic cells of the Ercc1 mutant mice. Importantly, we demonstrated that haploinsufficiency of the p65 NF-κB subunit partially rescued the osteoporosis phenotype of Ercc1−/Δ mice. Finally, pharmacological inhibition of the NF-κB signaling via an IKK inhibitor reversed cellular senescence and SASP in Ercc1−/Δ BMSCs. These results demonstrate that DNA damage drives

  4. Spatial variation in osteonal bone properties relative to tissue and animal age.

    PubMed

    Gourion-Arsiquaud, Samuel; Burket, Jayme C; Havill, Lorena M; DiCarlo, Edward; Doty, Stephen B; Mendelsohn, Richard; van der Meulen, Marjolein C H; Boskey, Adele L

    2009-07-01

    Little is known about osteonal bone mineral and matrix properties, although these properties are of major importance for the understanding of bone alterations related to age and bone diseases such as osteoporosis. During aging, bone undergoes modifications that compromise their structural integrity as shown clinically by the increase of fracture incidence with age. Based on Fourier transform infrared (FTIR) analysis from baboons between 0 and 32 yr of age, consistent systematic variations in bone properties as a function of tissue age are reported within osteons. The patterns observed were independent of animal age and positively correlated with bone tissue elastic behavior measured by nano-indentation. As long as tissue age is expressed as a percentage of the entire osteon radius, osteonal analyses can be used to characterize disease changes independent of the size of the osteon. These mineral and matrix analyses can be used to explain bone fragility. The mineral content (mineral-to-matrix ratio) was correlated with the animal age in both old (interstitial) and newly formed bone tissue, showing for the first time that age-related changes in BMC can be explain by an alteration in the mineralization process itself and not only by an imbalance in the remodeling process. PMID:19210217

  5. Age related changes in the bone tissue under conditions of hypokinesia

    NASA Technical Reports Server (NTRS)

    Podrushnyak, E. P.; Suslov, E. I.

    1980-01-01

    Microroentgenography of nine young people, aged 24-29, before and after hypokinesia (16-37 days strict bed rest), showed that the heel bone density of those with initially high bone density generally decreased and that of those with initially low bone density generally increased. X-ray structural analysis of the femurs of 25 corpses of accidentally killed healthy people, aged 18-70, data are presented and discussed, with the conclusion that the bone hydroxyapatite crystal structure stabilizes by ages 20 to 25, is stable from ages 25 to 60 and decreases in density after age 60. It is concluded that bone tissue structure changes, both with age, and in a comparatively short time in hypokinesia.

  6. Advanced paternal age and reproductive outcome.

    PubMed

    Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha

    2012-01-01

    Women have been increasingly delaying the start of motherhood in recent decades. The same trend is seen also for men. The influence of maternal age on fertility, chromosomal anomalies, pregnancy complications, and impaired perinatal and post-natal outcome of offspring, has been thoroughly investigated, and these aspects are clinically applied during fertility and pregestational counseling. Male aging and reproductive outcome has gained relatively less attention. The purpose of this review is to evaluate updated and relevant literature on the effect of paternal age on reproductive outcome. PMID:22157982

  7. Advanced paternal age and reproductive outcome

    PubMed Central

    Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha

    2012-01-01

    Women have been increasingly delaying the start of motherhood in recent decades. The same trend is seen also for men. The influence of maternal age on fertility, chromosomal anomalies, pregnancy complications, and impaired perinatal and post-natal outcome of offspring, has been thoroughly investigated, and these aspects are clinically applied during fertility and pregestational counseling. Male aging and reproductive outcome has gained relatively less attention. The purpose of this review is to evaluate updated and relevant literature on the effect of paternal age on reproductive outcome. PMID:22157982

  8. Additional evidence for bone technology in the southern African Middle Stone Age.

    PubMed

    d'Errico, Francesco; Henshilwood, Christopher S

    2007-02-01

    Few Middle Stone Age sites have yielded convincing evidence for a complex bone technology, a behavior often associated with the emergence of modern cultures. Here, we review the published evidence for Middle Stone Age bone tools from southern Africa, analyze an additional nine bone artifacts recently recovered from Middle Stone Age levels at Blombos Cave, describe an unpublished bone tool from probable Middle Stone Age levels at Peers Cave, examine a single bone awl found at Blombosch Sands (an open site near Blombos Cave), and reappraise marked bone artifacts and a bone point recovered from Klasies River. To determine the chronological and cultural attribution of these artifacts, document bone-manufacturing techniques associated with the southern African MSA, and discuss the symbolic significance of the markings present on some of these objects we use (1) available contextual information; (2) morphometric comparison of Later Stone Age, Modern San, and purported Middle Stone Age projectile points; (3) analysis of the carbon/nitrogen content of bone tools and faunal remains from Peers and Blombos caves; and (4) microscopic analysis of traces of manufacture and use. Previously undescribed bone artifacts from Blombos Cave include a massive point manufactured on weathered bone, two complete awls and two awl tips manufactured on small-sized mammal and bird bone, a probable projectile point with a tang manufactured by knapping and scraping, a shaft fragment modified by percussion, used as retoucher and bearing a set of incised lines on the middle of the periosteal surface, and two fragments with possible engravings. The point from Peers Cave can be assigned to the Middle Stone Age and bears tiny markings reminiscent of those recorded on projectile points from Blombos and used as marks of ownership on San arrow points. The awl from Blombosch Sands and the bone point from Klasies River can be attributed to the Later Stone Age. Two notched objects from Klasies are

  9. [Drivers of advanced age in traffic accidents].

    PubMed

    Bilban, Marjan

    2002-12-01

    The elderly are vulnerable and potentially unpredictable active participants in traffic who deserve special attention. Longer life expectancy entails a greater number of senior drivers, that is, persons with various health problems and difficulties accompanying old age. At the turn of the millennium, the share of population aged 65 or more in Slovenia was around 13%, and in 25 years it will be near as much as 19%. The share of drivers from this age group was 28% a year ago, and it is expected to reach about 54%. Numerous studies have shown that there are many differences in driving attitude between the young and the elderly. The young are by large active victims, and their main offense and cause of accident is speeding, while the elderly are more passive and their main offense is ignoring and enforcing the right of way. This paper focuses on the differences in the occurrence and type of injuries between the young and the elderly drivers, based on an analysis of all road accidents in Slovenia in the period between 1998-2000. Older people (over 65) caused only 4.7% of all road accidents (16.7% of all accidents involving pedestrians, 11.5% of all involving cyclists, 2.7% involving motorcyclists and 5% of all accidents involving car drivers). Of all accidents, 89.3% were without injuries, and the fatal outcome was registered in 0.4% accidents. Among the elderly (65-74 years of age), however, this share was 1%, and rising to 2.7% with the age 75 and above. By calculating the weight index, which discriminates between minor and severe injuries, and the fatal outcome, it was established that age groups 65-74 and > or = 75 cause three and five times greater damage, respectively than age groups from 18 to 54 years. With years, psychophysical changes lead to a drop in driving ability, which in turn increases the risk of road accidents. It is true that elderly people cause less traffic accidents (and also drive less) than the young, but when they are involved in an accident

  10. Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.

    PubMed

    Syed, Farhan A; Mödder, Ulrike Il; Roforth, Matthew; Hensen, Ira; Fraser, Daniel G; Peterson, James M; Oursler, Merry Jo; Khosla, Sundeep

    2010-11-01

    While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age-related bone loss, we sham-operated, ovariectomized, or ovariectomized and estrogen-replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin-) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six-month-old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham-operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age-related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham-operated mice. As compared with cells from young mice, lin- cells from aged/sham-operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age-related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. PMID:20499336

  11. Age determination in manatees using growth-layer-group counts in bone

    USGS Publications Warehouse

    Marmontel, M.; O'Shea, T.J.; Kochman, H.I.; Humphrey, S.R.

    1996-01-01

    Growth layers were observed in histological preparations of bones of known-age, known minimum-age, and tetracycline-marked free-ranging and captive Florida manatees (Trichechus manatus latirostris), substantiating earlier preliminary findings of other studies. Detailed analysis of 17 new case histories showed that growth-layer group (GLG) counts in the periotic bone were consistent with known age, or time since tetracycline administration, but were less reliable in other bones. GLG counts were also made in periotic bones of 1,196 Florida manatees of unknown age found dead from 1974 through 1991. These counts were conducted in order to assess variability and to determine relationships among estimated age, size, sex, and degree of bone resorption. Resorption can interfere with accuracy of GLG counts. This effect does not occur until ages greater than about 15 yr and body lengths greater than 300 cm are attained. GLGs were also observed in periotic bones of Antillean manatees (Trichechus manatus manatus) but were not validated against known-age specimens. Use of GLG counts in the periotic bone is suitable for application to studies of population dynamics and other age-related aspects of manatee biology.

  12. Predictors of Driving Outcomes in Advancing Age

    PubMed Central

    Emerson, Jamie L.; Johnson, Amy M.; Dawson, Jeffrey D.; Uc, Ergun Y.; Anderson, Steven W.

    2012-01-01

    This study aimed to develop predictive models for real-life driving outcomes in older drivers. Demographics, driving history, on-road driving errors, and performance on visual, motor, and neuropsychological test scores at baseline were assessed in 100 older drivers (ages 65–89 years [72.7]). These variables were used to predict time to driving cessation, first moving violation, or crash. Using Cox proportional hazards regression models, significant individual predictors for driving cessation were greater age and poorer scores on Near Visual Acuity, Contrast Sensitivity, Useful Field of View, Judgment of Line Orientation, Trail Making Test-Part A, Benton Visual Retention Test, Grooved Pegboard, and a composite index of overall cognitive ability. Greater weekly mileage, higher education, and “serious” on-road errors predicted moving violations. Poorer scores from Trail Making Test-Part B or Trail Making Test (B-A) and serious on-road errors predicted crashes. Multivariate models using “off-road” predictors revealed (1) age and Contrast Sensitivity as best predictors for driving cessation; (2) education, weekly mileage, and Auditory Verbal Learning Task-Recall for moving violations; and (3) education, number of crashes over the past year, Auditory Verbal Learning Task-Recall, and Trail Making Test (B-A) for crashes. Diminished visual, motor, and cognitive abilities in older drivers can be easily and noninvasively monitored with standardized off-road tests, and performances on these measures predict involvement in motor vehicle crashes and driving cessation, even in the absence of a neurological disorder. PMID:22182364

  13. Recent advances in vertebrate aging research 2009.

    PubMed

    Austad, Steven

    2010-06-01

    Among the notable trends seen in this year's highlights in mammalian aging research is an awakening of interest in the assessment of age-related measures of mouse health in addition to the traditional focus on longevity. One finding of note is that overexpression of telomerase extended life and improved several indices of health in mice that had previously been genetically rendered cancer resistant. In another study, resveratrol supplementation led to amelioration of several degenerative conditions without affecting mouse lifespan. A primate dietary restriction (DR) study found that restriction led to major improvements in glucoregulatory status along with provocative but less striking effects on survival. Visceral fat removal in rats improved their survival, although not as dramatically as DR. An unexpected result showing the power of genetic background effects was that DR shortened the lifespan of long-lived mice bearing Prop1(df), whereas a previous report in a different background had found DR to extend the lifespan of Prop1(df) mice. Treatment with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, enhanced the survival of even elderly mice and improved their vaccine response. Genetic inhibition of a TOR target made female, but not male, mice live longer. This year saw the mTOR network firmly established as a major modulator of mammalian lifespan. PMID:20331443

  14. Lack of association between free testosterone and bone density separate from age in elderly males.

    PubMed

    Drinka, P J; Olson, J; Bauwens, S; Voeks, S K; Carlson, I; Wilson, M

    1993-01-01

    It is unclear what proportion of the variance in bone density in elderly males is accounted for by testosterone status. We studied 112 ambulatory, elderly volunteers (mean age 71.7 years) and determined free testosterone (FT), as well as bone density measurements by photon absorptiometry at multiple sites. Our studies of 35 of these subjects 4 years later included morning FT and dual energy X-ray absorptiometry. There were no significant correlations between FT and bone density at multiple scanning sites with the effects of age partialed out. We suspect that our inability to detect a significant effect of FT on bone density was related to the relative strength of other determinants of bone density, as well as to the fact that FT values are far more dynamic than bone density. PMID:8453508

  15. Advances in multimodality molecular imaging of bone structure and function

    PubMed Central

    Lambers, Floor M; Kuhn, Gisela; Müller, Ralph

    2012-01-01

    The skeleton is important to the body as a source of minerals and blood cells and provides a structural framework for strength, mobility and the protection of organs. Bone diseases and disorders can have deteriorating effects on the skeleton, but the biological processes underlying anatomical changes in bone diseases occurring in vivo are not well understood, mostly due to the lack of appropriate analysis techniques. Therefore, there is ongoing research in the development of novel in vivo imaging techniques and molecular markers that might help to gain more knowledge of these pathological pathways in animal models and patients. This perspective provides an overview of the latest developments in molecular imaging applied to bone. It emphasizes that multimodality imaging, the combination of multiple imaging techniques encompassing different image modalities, enhances the interpretability of data, and is imperative for the understanding of the biological processes and the associated changes in bone structure and function relationships in vivo. PMID:27127622

  16. Sirt1 is involved in decreased bone formation in aged apolipoprotein E-deficient mice

    PubMed Central

    Hong, Wei; Xu, Xiao-ya; Qiu, Zhao-hui; Gao, Jian-jun; Wei, Zhan-ying; Zhen, Li; Zhang, Xiao-li; Ye, Zhi-bing

    2015-01-01

    Aim: Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE−/− mice. In this study we investigated the bone phenotype and metabolism in aged apoE−/− mice. Methods: Femurs and tibias were collected from 18- and 72-week-old apoE−/− mice and their age-matched wild-type (WT) littermates, and examined using micro-CT and histological analysis. Serum levels of total cholesterol, oxidized low-density lipoprotein (ox-LDL) and bone turnover markers were measured. Cultured bone mesenchymal stem cells (BMSCs) from tibias and femurs of 18-week-old apoE−/− mice were used in experiments in vitro. The expression levels of Sirt1 and Runx2 in bone tissue and BMSCs were measured using RT-PCR and Western blot analysis. Results: Compared with age-matched WT littermates, young apoE−/− mice exhibited high bone mass with increased bone formation, accompanied by higher serum levels of bone turnover markers OCN and TRAP5b, and higher expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. In contrast, aged apoE−/− mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h. Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs. Conclusion: In contrast to young apoE−/− mice, aged apoE−/− mice showe lower bone mass than age-matched WT mice. Long-lasting exposure to ox-LDL decreases the expression of Sirt1 and Runx2 in BMSCs, which may explain the decreased bone formation in aged apoE−/− mice. PMID:26592520

  17. PROGRESSIVE MECHANICAL BEHAVIOR OF HUMAN CORTICAL BONE IN TENSION FOR TWO AGE GROUPS

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Reyes, Michael J.; Wang, Xiaodu

    2007-01-01

    The capacity of bone for post-yield energy dissipation decreases with age. To gain information on the cause of such changes, we examined the mechanical behavior of human cadaveric bone as a function of progressive deformation. In this study, tensile specimens from tibiae of 9 middle aged and 8 elderly donors were loaded till failure in an incremental and cyclic (load-dwell-unload-dwell-reload) scheme. The elastic modulus, maximum stress, permanent strain, stress relaxation, viscoelastic time constant, plastic strain energy, elastic release strain energy, and hysteresis energy were determined at incremental strains of each loading cycle. Experimental results showed that elderly bone failed at much lower strains compared to middle aged bone, but little age-related differences were observed in the mechanical behavior of bone until the premature failure of elderly bone. Energy dissipation and permanent strain appeared to linearly increase with increasing strain, while non-linear changes occurred in the modulus loss and stress relaxation/time constant with increasing strain. Such changes suggest that two distinct stages may exist in the progressive deformation of bone. In Stage I, rapid damage accumulation and increased involvement of collagen in load bearing appeared to dominate the mechanical behavior of bone with limited energy dissipation (<20% of total energy dissipated), whereas Stage II is dominated by continuous plastic deformation, accompanied by major energy dissipation through all three pathways till failure. This study suggests that damaging mechanisms in bone vary with deformation and age affects the post-yield mechanisms causing a significant decline in the capacity of aged bone to dissipate energy. PMID:18437693

  18. Advanced imaging of the macrostructure and microstructure of bone

    NASA Technical Reports Server (NTRS)

    Genant, H. K.; Gordon, C.; Jiang, Y.; Link, T. M.; Hans, D.; Majumdar, S.; Lang, T. F.

    2000-01-01

    Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The

  19. Green tea polyphenols supplementation improves bone microstructure in orchidectomized middle-Aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our recent study shows that green tea polyphenols (GTP) attenuate trabecular bone loss in ovariectomized middle-aged female rats. To investigate whether GTP prevents bone loss in male rats, 40 rats with and without oriectomy (ORX) were assigned to 4 groups in a 2 (sham vs. ORX)× 2 (no GTP and 0.5% G...

  20. Targeting bone metabolism in patients with advanced prostate cancer: current options and controversies.

    PubMed

    Todenhöfer, Tilman; Stenzl, Arnulf; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-01-01

    Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC) who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL), antiresorptive agents have been shown to improve bone mineral density (BMD) and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs) in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy. PMID:25802521

  1. Recent Advances in Bone-Targeted Therapies of Metastatic Prostate Cancer

    PubMed Central

    Deng, Xiyun; He, Guangchun; Liu, Junwen; Luo, Feijun; Peng, Xiaoning; Tang, Shigang; Gao, Zhiyong; Lin, Qinlu; Keller, Jill M.; Yang, Tao; Keller, Evan T.

    2014-01-01

    Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved. PMID:24767837

  2. Age-related switch of bone mass in p47phox deficient mice through increased inflammatory milieu in bone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Excessive accumulation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals, has been suggested to be the leading cause of many inflammatory and degener...

  3. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus.

    PubMed

    Saito, M; Marumo, K

    2010-02-01

    Collagen cross-linking, a major post-translational modification of collagen, plays important roles in the biological and biomechanical features of bone. Collagen cross-links can be divided into lysyl hydroxylase and lysyloxidase-mediated enzymatic immature divalent cross-links,mature trivalent pyridinoline and pyrrole cross-links, and glycation- or oxidation-induced non-enzymatic cross-links(advanced glycation end products) such as glucosepane and pentosidine. These types of cross-links differ in the mechanism of formation and in function. Material properties of newly synthesized collagen matrix may differ in tissue maturity and senescence from older matrix in terms of crosslink formation. Additionally, newly synthesized matrix in osteoporotic patients or diabetic patients may not necessarily be as well-made as age-matched healthy subjects. Data have accumulated that collagen cross-link formation affects not only the mineralization process but also microdamage formation. Consequently, collagen cross-linking is thought to affect the mechanical properties of bone. Furthermore,recent basic and clinical investigations of collagen cross-links seem to face a new era. For instance, serum or urine pentosidine levels are now being used to estimate future fracture risk in osteoporosis and diabetes. In this review, we describe age-related changes in collagen cross-links in bone and abnormalities of cross-links in osteoporosis and diabetes that have been reported in the literature. PMID:19760059

  4. Characterization of eight different tetracyclines: advances in fluorescence bone labeling

    PubMed Central

    Pautke, Christoph; Vogt, Stephan; Kreutzer, Kilian; Haczek, Cornelia; Wexel, Gabriele; Kolk, Andreas; Imhoff, Andreas B; Zitzelsberger, Horst; Milz, Stefan; Tischer, Thomas

    2010-01-01

    Polychrome sequential labeling with fluorochromes is a standard technique for the investigation of bone formation and regeneration processes in vivo. However, for human application, only tetracycline and its derivates are approved as fluorochromes. Therefore, the aim of this study was to determine the fluorescence characteristics of the different tetracycline derivates to assess the feasibility of sequential in vivo bone labeling using distinguishable fluorochromes. Eight different tetracycline derivates were injected subcutaneously into growing rats as a single dose or sequentially in different combinations. After preparation of resin-embedded undecalcified bone sections, the fluorescence properties of the tetracycline derivates in bone were analyzed using conventional fluorescence microscopy, spectral image analysis and confocal laser scanning microscopy. Each tetracycline derivate exhibited a characteristic fluorescence spectrum, but the differences between them were small. Chlortetracycline could be discriminated reliably from all other derivates and could therefore be combined with any other tetracycline derivate for reliably distinguishable double labeling. Tetracycline itself exhibited the brightest fluorescence of all the investigated derivates. Interestingly, in conventional microscopy the same tetracycline derivative can appear in different colours to the human eye, even if spectral analysis confirmed identical emission peaks. In conclusion, the data suggest that fluorescence double labeling of bone is feasible using appropriate tetracycline derivates in combination with spectral imaging modalities. PMID:20456523

  5. Adaptation of Cancellous Bone to Aging and Immobilization in Growing Rats

    NASA Technical Reports Server (NTRS)

    Chen, Meng-Meng; Jee, Webster S. S.; Ke, Hua-Zhu; Lin, Bai-Yun; Li, Qing-Nan; Li, Xiao-Jian

    1992-01-01

    Two-and-half-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 tLm sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55 to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at I and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59% at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobiliza- tion. However, bone formation rate-tissue area referent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9-month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in

  6. Adaptation of Cancellous Bone to Aging and Immobilization in Growing Rats

    NASA Technical Reports Server (NTRS)

    Chen, Meng Meng; Jee, Webster S. S.; Ke, Hua Zhu; Lin, Bia Yun; Li, Qing Nan; Li, Xiao Jian

    1992-01-01

    Two-and-a half month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double-fluorescent labeled 20 micron sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55% to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at 1 and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59%c at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobilization. However, bone formation rate-tissue area referent was depressed (-65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9 month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated

  7. Age- and Sex-Related Changes in Bone Microarchitecture and Estimated Strength: A Three-Year Prospective Study Using HRpQCT.

    PubMed

    Shanbhogue, Vikram V; Brixen, Kim; Hansen, Stinus

    2016-08-01

    Although projections from cross-sectional studies have shown that bone loss leading to osteoporosis begins around menopause in women and later in life in men, this has not been examined longitudinally in population-based studies using high-resolution technology capable of distinguishing cortical (Ct) and trabecular (Tb) bone microarchitecture. The aim of this 3-year prospective study was to investigate age- and sex-related changes in bone compartment-specific geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated strength. The distal radius and tibia were imaged at baseline and after 3 years (median 3.0; range, 2.7 to 3.9 years) using high-resolution peripheral computed tomography (HRpCT) in an age- and sex-stratified, population-based, random sample of white men and women (n = 260) aged 21 to 82 years. In general, at the radius and tibia there was a moderate annual increase in cortical thickness (Ct.Th) that seemed to offset the increase in cortical porosity (Ct.Po), resulting in net annual increase in cortical vBMD (Ct.vBMD) in premenopausal women and young men. With advancing age, postmenopausal women displayed significant bone loss with decreased trabecular vBMD (Tb.vBMD) (due to loss of entire trabeculae) and Ct.vBMD (manifested as increase in Ct.Po and decrease in Ct.Th) at the radius, and a decline in Ct.vBMD (with increasing Ct.Po) at the tibia, resulting in loss of estimated bone strength. In contrast, men had a lower rate of bone loss with advancing age with smaller increases in Ct.Po at both the skeletal sites. In summary, the pattern of bone loss in men and women was discrepant, with women losing more bone than men with aging, although with a dominance of cortical over trabecular bone loss at the peripheral sites in both sexes. This conforms to epidemiological evidence that most fractures occurring in old age are predominantly at cortical peripheral sites, with women having a higher incidence of fractures than men at any

  8. [Bone aging and frailty syndrome after 10 years of ARV treatment in Senegal].

    PubMed

    Cournil, A; Eymard-Duvernay, S; Diouf, A

    2014-10-01

    This study compares two indicators of aging (bone loss and frailty syndrome) between patients of the cohort and age- and sex-matched subjects from the general population in Dakar. It shows that patients had a lower mineral bone density. By contrast, the prevalence of frailty (an indicator of general health status and physical condition) among patients was similar to the general population. PMID:24615435

  9. Microstructural and compositional contributions towards the mechanical behavior of aging human bone measured by cyclic and impact reference point indentation.

    PubMed

    Abraham, Adam C; Agarwalla, Avinesh; Yadavalli, Aditya; Liu, Jenny Y; Tang, Simon Y

    2016-06-01

    The assessment of fracture risk often relies primarily on measuring bone mineral density, thereby accounting for only a single pathology: the loss of bone mass. However, bone's ability to resist fracture is a result of its biphasic composition and hierarchical structure that imbue it with high strength and toughness. Reference point indentation (RPI) testing is designed to directly probe bone mechanical behavior at the microscale in situ, although it remains unclear which aspects of bone composition and structure influence the results at this scale. Therefore, our goal in this study was to investigate factors that contribute to bone mechanical behavior measured by cyclic reference point indentation, impact reference point indentation, and three-point bending. Twenty-eight female cadavers (ages 57-97) were subjected to cyclic and impact RPI in parallel at the unmodified tibia mid-diaphysis. After RPI, the middiaphyseal tibiae were removed, scanned using micro-CT to obtain cortical porosity (Ct.Po.) and tissue mineral density (TMD), then tested using three-point bending, and lastly assayed for the accumulation of advanced glycation end-products (AGEs). Both the indentation distance increase from cyclic RPI (IDI) and bone material strength index from impact RPI (BMSi) were significantly correlated with TMD (r=-0.390, p=0.006; r=0.430, p=0.002; respectively). Accumulation of AGEs was significantly correlated with IDI (r=0.281, p=0.046), creep indentation distance (CID, r=0.396, p=0.004), and BMSi (r=-0.613, p<0.001). There were no significant relationships between tissue TMD or AGEs accumulation with the quasi-static material properties. Toughness decreased with increasing tissue Ct.Po. (r=-0.621, p<0.001). Other three-point bending measures also correlated with tissue Ct.Po. including the bending modulus (r=-0.50, p<0.001) and ultimate stress (r=-0.56, p<0.001). The effects of Ct.Po. on indentation were less pronounced with IDI (r=0.290, p=0.043) and BMSi (r=-0.299, p

  10. Graphene and its nanostructure derivatives for use in bone tissue engineering: Recent advances.

    PubMed

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2016-05-01

    Tissue engineering and regenerative medicine represent areas of increasing interest because of the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Graphene and its derivatives have attracted much interest for applications in bone tissue engineering. For this purpose, this review focuses on more recent advances in tissue engineering based on graphene-biomaterials from 2013 to May 2015. The purpose of this article was to give a general description of studies of nanostructured graphene derivatives for bone tissue engineering. In this review, we highlight how graphene family nanomaterials are being exploited for bone tissue engineering. Firstly, the main requirements for bone tissue engineering were discussed. Then, the mechanism by which graphene based materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. In addition, graphene-based bioactive glass, as a potential drug/growth factor carrier, was reviewed which includes the composition-structure-drug delivery relationship and the functional effect on the tissue-stimulation properties. Also, the effect of structural and textural properties of graphene based materials on development of new biomaterials for production of bone implants and bone cements were discussed. Finally, the present review intends to provide the reader an overview of the current state of the graphene based biomaterials in bone tissue engineering, its limitations and hopes as well as the future research trends for this exciting field of science. PMID:26748447

  11. Age and disease-related changes in the mineral of bone.

    PubMed

    Grynpas, M

    1993-01-01

    Bone mineralization changes with age and disease. The distribution of mineral particles in a given bone (mineralization profile) has been studied using density fractionation as well as microradiography and electron backscattering imaging. The biological determinant of mineralization is the rate of turnover. During rapid growth and periods of high remodeling, mineralization is shifted towards lower mineral density (hypomineralization). During aging and periods of low remodeling, mineralization is shifted towards higher mineral densities (hypermineralization). Chemicals can also influence the mineralization profile of bone. Fluoride induces hypermineralization by stabilizing the apatite lattice and reducing bone mineral solubility, whereas strontium induces hypomineralization by loosening the apatite lattice and increasing bone mineral solubility. Drugs such as bisphosphonates induce hypermineralization by inhibiting resorption and acting as crystal poison. Finally, mineralization can be impaired by defects as in rickets and osteomalacia or made excessive by continuous accretion of mineral without resorption as in osteopetrosis. PMID:8275381

  12. Age-related differences in the bone mineralization pattern of rats following exercise

    SciTech Connect

    McDonald, R.; Hegenauer, J.; Saltman, P.

    1986-07-01

    The effect of 12 weeks of treadmill exercise on the mineralization of trabecular and cortical bone was studied in rats 7, 14, and 19 months of age. Bone mineralization was evaluated by measuring concentrations of Ca, Mg, and hydroxyproline as well as uptake of 45Ca concentration in the femur, humerus, rib and calvaria. The 7- and 14-month-old rats increased mineralization in those cortical bones directly involved in exercise. The 19-month animal responded to exercise by increasing mineralization in all bones examined, including the nonweight bearing trabecular calvaria and cortical rib. From these data, it is apparent that the older animals undergo a total skeletal mineralization in response to exercise compared with local adaptation in the younger animal. Further, we provide evidence to support the use of the rat as a model in which to study mammalian bone physiology during the aging process.

  13. Optimizing the assessment of age-related changes in trabecular bone

    NASA Astrophysics Data System (ADS)

    Kubik, T.; Pasowicz, M.; Tabor, Z.; Rokita, E.

    2002-05-01

    The goal of this study was to develop an optimal procedure to determine age-related changes in trabecular bone. The investigations were based on two-dimensional images of the human vertebral trabecular bone specimens. The following indices of trabecular structure were considered: bone volume/total volume, star volume of the marrow cavity, Euler number and the probability of disconnection (straightforwardly connected with the number of separated parts of the network). To follow precisely the changes in the trabecular structure with age, a computer simulation model was used. Up to 35 years of physiological remodelling were simulated. The validation of the model calculations was based on a quantitative comparison with the data measured for older individuals. The simulations confirmed that the description of the age-related changes in the trabecular bone by means of the architectural parameter (star volume) constitutes a promising tool for subjects older than ~50 years. For individuals younger than ~50 years bone mineral density (bone volume/total volume) seems to be the best suited descriptor. The results suggest that the optimal diagnostic procedure is age-dependent and should not be limited to the bone mineral density measurement. The clinical usefulness of the procedure has been validated by examination of the CT images.

  14. Determinants of bone mineral density, bone mineral content, and body composition in a cohort of healthy children: influence of sex, age, puberty, and physical activity.

    PubMed

    Ausili, Emanuele; Rigante, Donato; Salvaggio, Elio; Focarelli, Benedetta; Rendeli, Claudia; Ansuini, Valentina; Paolucci, Valentina; Triarico, Silvia; Martini, Lucilla; Caradonna, Paolo

    2012-09-01

    Interventions directed to the recognition of abnormal bone mineral density, bone mineral content, and body composition in the pediatric age require the definition of factors influencing bone mass acquisition during growth. We have evaluated in a cross-sectional manner by dual-energy X-ray absorptiometry the impact of sex, age, puberty, and physical activity on total body areal bone mineral density, regional (lumbar and femoral) bone mineral densities, bone mineral content, and body composition (fat mass and lean mass) in a cohort of 359 healthy Italian children aged 3-14 years and investigated their specific contribution to bone mass accrual. Statistical multiple regression analysis was performed dividing the population in pre- and post-pubertal groups. Bone mineral density at the lumbar spine has resulted equally distributed in both sexes before puberty while has resulted higher at the femoral necks in males at whatever age. A significant effect on bone mass acquisition was exerted by male sex and lean mass. In the areas where the cortical bone is prevalent, males of the pre-pubertal group have presented the highest values; in the areas where the cancellous bone is prevalent, both sexes were equivalent until the age of 9 years, but after this age, females have presented higher increases, probably related to the inferior dimensional development of lumbar vertebrae. Conclusively, male sex and lean mass seem to represent independent predictors of bone mass accrual in the cortical bone of the examined children, while female sex and pubertal maturation are independent predictors of bone mass accrual in the trabecular bone. PMID:21809005

  15. Advance directives as an instrument in an ageing Europe.

    PubMed

    Goffin, Tom

    2012-04-01

    Advance directives are written or oral statements that are intended to govern healthcare decision-making for their authors, for both positive and negative decisions, should they lose decisional capacity in the future. In a Europe which is facing an ageing population, advance directives play an increasing role to (help) formulate the wishes from elderly patient once they start losing the capacity to decide independently. Advance directives should not only be used as a formulation of the patients' previously made decision, but can also be used as guidelines to better understand the previous expressed wishes of the patient. If the advance directive is formulated in too vague form, the healthcare proxy and/or the healthcare trustee can help the physician interpret the directive. This broader approach towards advance directives is reflected in the case-law of the European Court of Human Rights, as well as on the European legislative level. PMID:22558655

  16. Osteoporotic-like effects of cadmium on bone mineral density and content in aged ovariectomized beagles

    SciTech Connect

    Sacco-Gibson, N.; Abrams, J.; Chaudhry, S.; Hurst, D.; Peterson, D.; Bhattacharyya, M.

    1992-12-31

    Our purpose was to evaluate the effects of ovariectomy in conjunction with cadmium (Cd) exposure on bone. Aged female beagles with {sup 45}Ca-labeled skeletons ovariectomized and exposed to Cd. Successive vertebral scans by dual photon absorptiometry monitored changes in bone mineral density (BMD) in each dog with time. Results showed that ovariectomy or Cd exposure alone caused significant decreases in BMD; ovariectomy with Cd exposure caused the greatest decrease. Ovariectomy alone did not decrease BMD in the distal end or mid-shaft of the tibia while BMD of the distal tibia decreased significantly due to Cd exposure alone. Combination treatment resulted in significant decreases in BMD of both tibial regions. At necropsy, tibiae, humeri, lumbar vertebrae and ribs were obtained for biochemical analysis. No group-to-group differences in bone weights (wet, dry, ash), in ash/dry ratios, or in long bone and vertebral Ca/dry or Ca/ash ratios were observed. Significantly higher total {sup 45}Ca content and {sup 45}Ca/dry and {sup 45}Ca/ash ratios were observed in long bones and vertebrae of OV- and OV+ groups. In contrast, intact ribs showed significantly decreased Ca/dry and Ca/ash ratios compared to the SO-group. Quartered ribs demonstrated regional responses to specific treatment; decreases in total Ca content were greatest in the mid-rib region ({minus}36 to {minus}46%). Results suggest that in the aged female beagle, bone mineral loss associated with estrogen depletion is not only related to bone type (trabecular versus cortical) but also to bone Ca pools. Our results also suggest that a regional heterogeneity of bone plays a role in responsiveness to ovariectomy and Cd exposure. These aspects suggest that Cd is an exogenous factor affecting bone mineral loss independently of estrogen depletion. However, estrogen depletion primes bone for responsiveness to Cd-induced bone mineral loss.

  17. Age-related decrements in bone mineral density in women over 65

    NASA Technical Reports Server (NTRS)

    Steiger, P.; Cummings, S. R.; Black, D. M.; Spencer, N. E.; Genant, H. K.

    1992-01-01

    Age-related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population-based lists in four cities in the United States. Bone density in g/cm2 was measured by single-photon absorptiometry (SPA) and dual x-ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65-69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from -0.82% at the femoral neck and trochanter to -1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine.

  18. Digital hand atlas and computer-aided bone age assessment via the Web

    NASA Astrophysics Data System (ADS)

    Cao, Fei; Huang, H. K.; Pietka, Ewa; Gilsanz, Vicente

    1999-07-01

    A frequently used assessment method of bone age is atlas matching by a radiological examination of a hand image against a reference set of atlas patterns of normal standards. We are in a process of developing a digital hand atlas with a large standard set of normal hand and wrist images that reflect the skeletal maturity, race and sex difference, and current child development. The digital hand atlas will be used for a computer-aided bone age assessment via Web. We have designed and partially implemented a computer-aided diagnostic (CAD) system for Web-based bone age assessment. The system consists of a digital hand atlas, a relational image database and a Web-based user interface. The digital atlas is based on a large standard set of normal hand an wrist images with extracted bone objects and quantitative features. The image database uses a content- based indexing to organize the hand images and their attributes and present to users in a structured way. The Web-based user interface allows users to interact with the hand image database from browsers. Users can use a Web browser to push a clinical hand image to the CAD server for a bone age assessment. Quantitative features on the examined image, which reflect the skeletal maturity, will be extracted and compared with patterns from the atlas database to assess the bone age. The relevant reference imags and the final assessment report will be sent back to the user's browser via Web. The digital atlas will remove the disadvantages of the currently out-of-date one and allow the bone age assessment to be computerized and done conveniently via Web. In this paper, we present the system design and Web-based client-server model for computer-assisted bone age assessment and our initial implementation of the digital atlas database.

  19. The effects of advanced paternal age on fertility

    PubMed Central

    Kovac, Jason R; Addai, Josephine; Smith, Ryan P; Coward, Robert M; Lamb, Dolores J; Lipshultz, Larry I

    2013-01-01

    Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life. PMID:23912310

  20. [Determinants of bone quality and strength independent of bone remodeling].

    PubMed

    Saito, Mitsuru; Marumo, Keishi

    2016-01-01

    Bone mineral density(BMD)and bone microstructure are regulated mainly by bone remodeling. In contrast, bone collagen enzymatic immature and mature cross-links and advanced glycation end products such as pentosidine and carboxyl methyl lysine are affected by various factors. Aging bone tissue is repaired in the process of bone remodeling. However, deterioration of bone material properties markedly advances due to increases in oxidative stress, glycation stress, reactive oxygen species, carbonyl stress associated with aging and reduced sex hormone levels, and glucocorticoid use. To improve bone material properties in osteoporosis, we should use different drug (Saito M, Calcif Tissue Int, REVIEW, 97;242-261, 2015). In this review, we summarized determinants of bone quality and strength independent of bone remodeling. PMID:26728528

  1. Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

    PubMed

    Tikhonova, Maria A; Ting, Che-Hao; Kolosova, Nataliya G; Hsu, Chao-Yu; Chen, Jian-Horng; Huang, Chi-Wen; Tseng, Ging-Ting; Hung, Ching-Sui; Kao, Pan-Fu; Amstislavskaya, Tamara G; Ho, Ying-Jui

    2015-10-31

    Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis. PMID:26387656

  2. Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications

    NASA Technical Reports Server (NTRS)

    Charles, H. K. Jr; Beck, T. J.; Feldmesser, H. S.; Magee, T. C.; Spisz, T. S.; Pisacane, V. L.

    2001-01-01

    An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

  3. The Relationship Between Greater Prepubertal Adiposity, Subsequent Age of Maturation, and Bone Strength During Adolescence.

    PubMed

    Glass, Natalie A; Torner, James C; Letuchy, Elena M; Burns, Trudy L; Janz, Kathleen F; Eichenberger Gilmore, Julie M; Schlechte, Janet A; Levy, Steven M

    2016-07-01

    This longitudinal study investigated whether greater prepubertal adiposity was associated with subsequent timing of maturation and bone strength during adolescence in 135 girls and 123 boys participating in the Iowa Bone Development Study. Greater adiposity was defined using body mass index (BMI) data at age 8 years to classify participants as overweight (OW, ≥85th percentile for age and sex) or healthy weight (HW). Maturation was defined as the estimated age of peak height velocity (PHV) based on a series of cross-sectional estimates. Measurements were taken at ages 11, 13, 15, and 17 years for estimates of body composition by dual-energy X-ray absorptiometry (DXA), bone compression (bone strength index), and torsion strength (polar strength-strain index) at the radius and tibia by pQCT, and femoral neck bending strength (section modulus) by hip structural analysis. Bone strength in OW versus HW were evaluated by fitting sex-specific linear mixed models that included centered age (visit age - grand mean age of cohort) as the time variable and adjusted for change in fat mass, and limb length in model 1. Analyses were repeated using biological age (visit age - age PHV) as the time variable for model 1 with additional adjustment for lean mass in model 2. BMI was negatively associated with age of maturation (p < 0.05). OW versus HW girls had significantly greater bone strength (p < 0.001) in model 1, whereas OW versus HW boys had significantly greater bone strength (p < 0.001) at the tibia and femoral neck but not radius (p > 0.05). Analyses were repeated using biological age, which yielded reduced parameter estimates for girls but similar results for boys (model 1.) Differences were no longer present after adjustment for lean mass (model 2) in girls (p > 0.05) whereas differences at the tibia were sustained in boys (p < 0.05). These findings demonstrate sex- and site-specific differences in the associations between adiposity, maturation, and

  4. Influence of age, sex and calendar year on lifetime accumulated red bone marrow dose from diagnostic radiation exposure.

    PubMed

    Hoffmann, Wolfgang; Meiboom, Merle Friederike; Weitmann, Kerstin; Terschüren, Claudia; von Boetticher, Heiner

    2013-01-01

    Our aim is to evaluate the relevance of different factors influencing lifetime accumulated red bone marrow dose, such as calendar year, age and sex. The lifetime dose was estimated for controls interviewed in person (N = 2811, 37.5% women) of the population-based representative Northern Germany Leukemia and Lymphoma Study. Data were assessed in standardized computer-assisted personal interviews. The calculation of doses is based on a comprehensive quantification model including calendar year, sex, kind of examination, and technical development. In multivariate regression models the annual red bone marrow dose was analyzed depending on age, sex and calendar year to consider simultaneously temporal changes in radiologic practice and individual risk factors. While the number of examinations continuously rises over time, the dose shows two peaks around 1950 and after 1980. Men are exposed to higher doses than woman. Until 1970 traditional examinations like conventional and mass screening examinations caused the main dose. They were then replaced by technically advanced examinations mainly computed tomography and cardiac catheter. The distribution of the red bone marrow dose over lifetime depends highly on the technical standards and radiation protection survey. To a lesser extent it is influenced by age and sex of the subjects. Thus epidemiological studies concerning the assessment of radiation exposure should consider the calendar year in which the examination was conducted. PMID:24244286

  5. Is Animal Age a Factor In the Response of Bone to Spaceflight?

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E. R.; Garetto, L. P.; Doty, S. B.; Halloran, B. P.; Turner, R. T.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    The rodent bone response to spaceflight may be influenced by a multitude of actors including flight duration, strain, and housing. Review of bone formation rates during spaceflight suggests that age may also play a role in the response. Weanling rats show fewer bone changes than older rats. To determine if the long bones of weanling rats were insensitive to weight-bearing, a hindlimb unloading experiment was conducted simultaneously with a 9d shuttle flight in 34d old group-housed male rats. All animals were injected with bone markers 7d and 1d before flight and euthanized at landing, 24hr, and 72hr following recovery. If no differences in body weight, bone length, or bone formation at the tibiofibular junction were noted at the different time points, data were combined for each group. No significant differences in body weight were found at any time period among the groups. The humerus, tibia, and femur elongated significantly during the flight period with no difference in lengths between groups at the end of the flight period. The group-housed flight rats showed no change in cortical bone formation rate compared to preflight values, flight controls, or vivarium controls. However, the hindlimb unloading group showed a significant 30% decrease in bone formation rate compared to all other groups. Individually-housed 38d old animals flown for 14d showed approx. 10% suppression of cortical growth. We speculate that the mechanical threshold required for cross-sectional bone growth is reached in group-house weanling rats during spaceflight, perhaps, through physical interactions, and that the weanling animals are sensitive to loading. However, the threshold is not fully reached in either singly-housed flight or hindlimb unloaded weanling rats. Older singly-housed flight animals appear to show equal or greater bone changes compared to hindlimb unloaded rats. We conclude that age, flight duration, strain, and housing have important roles in rodent skeletal responses to

  6. Total bone calcium in normal women: effect of age and menopause status

    SciTech Connect

    Gallagher, J.C.; Goldgar, D.; Moy, A.

    1987-12-01

    Bone density in different regions of the skeleton was measured in 392 normal women aged 20-80 years by dual photon absorpiometry. In premenopausal women, aged 25-50 years, multiple regression analysis of regional bone density on age, height, and weight showed a small significant decrease in total bone density (less than 0.01) but no significant change in other regions of the skeleton. In postmenopausal women there were highly significant decreases in all regions of the skeleton (p less than 0.001), and bone density in these areas decreased as a logarithmic function of years since menopause. Based on multiple regression analyses, the decrease in spine density and total bone calcium was 2.5-3.0 times greater in the 25 years after menopause than the 25 years before menopause. The largest change, however, occurred in the first five years after menopause. During this time the estimated annual change in spine density and total bone calcium was about 10 times greater than that in the premenopausal period. These results demonstrate the important effect of the menopause in determining bone mass in later life.

  7. Familial resemblance of bone turnover rate in men aged 40 and over-the MINOS study.

    PubMed

    Nagy, Hoda; Feyt, Clément; Chapurlat, Roland; Szulc, Pawel

    2013-03-01

    Familial resemblance of bone mineral density (BMD) is well known in both sexes. Fewer data concern the familial resemblance of bone turnover markers (BTMs) and bone size in men. Our aim was to assess the correlation of BMD, bone size, BTM levels and hormones regulating bone turnover in 50 pairs of brothers aged ≥ 40 and 50 pairs of unrelated men matched for age, weight and height. BMD was measured at the lumbar spine, hip, forearm and whole body. We measured serum osteocalcin (OC), bone-specific alkaline phosphatase (bone ALP), N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) as well as urinary free and total deoxypyridinoline (DPD) and CTX-I. After adjustment for age, weight, bioavailable 17β-estradiol, and parathyroid hormone, all the BTMs (except bone ALP) were significantly correlated in the brothers (ICC = 0.36-0.64). Most of these correlations were significantly stronger than in the unrelated men. Bone size correlated significantly between the brothers (ICC = 0.55-0.65). These correlations were significantly stronger than in the unrelated men. BMD correlated between the brothers at most of the skeletal sites and, for some of them, more strongly than in the unrelated men. Serum levels of LDL-cholesterol and triglycerides were significantly correlated in the brothers, but not more strongly than in the unrelated men. BTM levels correlated independently in the brothers aged ≥ 40, when their shared environment was limited. These data suggest a substantial hereditary determinism of the BTM levels in men. PMID:23179229

  8. Reproduction at an advanced maternal age and maternal health.

    PubMed

    Sauer, Mark V

    2015-05-01

    Advanced age is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. These concerns are based on centuries-old observations, yet women are delaying childbearing to pursue educational and career goals in greater numbers than ever before. As a result, reproductive medicine specialists are treating more patients with age-related infertility and recurrent pregnancy loss, while obstetricians are faced with managing pregnancies often complicated by both age and comorbidities. The media portrayal of a youthful but older woman, able to schedule her reproductive needs and balance family and job, has fueled the myth that "you can have it all," rarely characterizing the perils inherent to advanced-age reproduction. Reproductive medicine specialists and obstetrician/gynecologists should promote more realistic views of the evidence-based realities of advanced maternal age pregnancy, including its high-risk nature and often compromised outcomes. Doctors should also actively educate both patients and the public that there is a real danger of childlessness if individuals choose to delay reproduction. PMID:25934599

  9. Effect of Aging on the Toughness of Human Cortical Bone: Evaluation by R-Curves

    SciTech Connect

    Kinney, J

    2004-10-08

    Age-related deterioration of the fracture properties of bone, coupled with increased life expectancy, are responsible for increasing incidence of bone fracture in the elderly, and hence, an understanding of how its fracture properties degrade with age is essential. The present study describes ex vivo fracture experiments to quantitatively assess the effect of aging on the fracture toughness properties of human cortical bone in the longitudinal direction. Because cortical bone exhibits rising crack-growth resistance with crack extension, unlike most previous studies the toughness is evaluated in terms of resistance-curve (R-curve) behavior, measured for bone taken from wide range of age groups (34-99 years). Using this approach, both the ex vivo crack-initiation and crack-growth toughness are determined and are found to deteriorate with age; the initiation toughness decreases some 40% over six decades from 40 to 100 years, while the growth toughness is effectively eliminated over the same age range. The reduction in crack-growth toughness is considered to be associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging in the wake of the crack.

  10. Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies show that green tea polyphenols (GTP) attenuate bone loss and microstructure deterioration in ovariectomized aged female rats, a model of postmenopausal osteoporosis. However, it is not known if such an osteo-protective role of GTP is demonstrable in androgen-deficient aged rats, a mo...

  11. Infection susceptibility and immune senescence with advancing age replicated in accelerated aging Lmna(Dhe) mice.

    PubMed

    Xin, Lijun; Jiang, Tony T; Kinder, Jeremy M; Ertelt, James M; Way, Sing Sing

    2015-12-01

    Aging confers increased susceptibility to common pathogens including influenza A virus. Despite shared vulnerability to infection with advancing age in humans and rodents, the relatively long time required for immune senescence to take hold practically restricts the use of naturally aged mice to investigate aging-induced immunological shifts. Here, we show accelerated aging Lmna(Dhe) mice with spontaneous mutation in the nuclear scaffolding protein, lamin A, replicate infection susceptibility, and substantial immune cell shifts that occur with advancing age. Naturally aged (≥ 20 month) and 2- to 3-month-old Lmna(Dhe) mice share near identically increased influenza A susceptibility compared with age-matched Lmna(WT) control mice. Increased mortality and higher viral burden after influenza infection in Lmna(Dhe) mice parallel reduced accumulation of lung alveolar macrophage cells, systemic expansion of immune suppressive Foxp3⁺ regulatory T cells, and skewed immune dominance among viral-specific CD8⁺T cells similar to the immunological phenotype of naturally aged mice. Thus, aging-induced infection susceptibility and immune senescence are replicated in accelerated aging Lmna(Dhe) mice. PMID:26248606

  12. Comparison of bone collagen and osteocalcin for determination of radiocarbon ages and paleodietary reconstruction

    NASA Astrophysics Data System (ADS)

    Ajie, Henry O.; Hauschka, Peter V.; Kaplan, Isaac R.; Sobel, Harry

    1991-11-01

    Osteocalcin, a gamma-carboxyglutamic acid containing bone protein, is tightly bound to the hydroxyapatite matrix of bone, and as a consequence it is relatively more stable than the dominant protein, collagen. Its distribution in nature is limited to vertebrates. Osteocalcin and collagen have been isolated from modern and fossil bone samples of different organisms in different depositional environments for analysis of their δ 13C , δ 15N and 14C content. Whereas collagen is susceptible t aqueous weathering, hydrolysis, solubilization and removal, as well as contamination by soil amino acids or peptides, osteocalcin is more strongly bonded to the apatite matrix of the bone and hence less prone to loss or replacement by contaminants. We present evidence suggesting that osteocalcin may be a more suitable protein fraction for obtaining accurate 14C age estimates and/or δ 13C and δ 15N for paleodietary reconstruction from bone samples.

  13. Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years.

    PubMed

    Rosario, Pedro Weslley

    2008-12-01

    The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged < 65 years. Forty-eight women with SCH were evaluated. The control group consisted of 48 euthyroid volunteers. The mean symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women with SCH showed a significant increase in serum markers of bone formation and resorption. In addition, bone mineral density (BMD) was lower in the femoral neck but not in the lumbar spine in patients before menopause, whereas a lower BMD was observed at both sites in postmenopausal patients. SCH is not completely asymptomatic in women aged < 65 years, and is associated with heart abnormalities and with increased bone turnover and reduced BMD even before menopause. PMID:19197452

  14. Aging and the 4-kHz Air-Bone Gap

    ERIC Educational Resources Information Center

    Nondahl, David M.; Tweed, Ted S.; Cruickshanks, Karen J.; Wiley, Terry L.; Dalton, Dayna S.

    2012-01-01

    Purpose: In this study, the authors assessed age- and sex-related patterns in the prevalence and 10-year incidence of 4-kHz air-bone gaps and associated factors. Method: Data were obtained as part of the longitudinal, population-based Epidemiology of Hearing Loss Study ( Cruickshanks et al., 1998). An air-bone gap at 4 kHz was defined as an…

  15. Histone deacetylase 3 is required for maintenance of bone mass during aging

    PubMed Central

    McGee-Lawrence, Meghan E.; Bradley, Elizabeth W.; Dudakovic, Amel; Carlson, Samuel W.; Ryan, Zachary C.; Kumar, Rajiv; Dadsetan, Mahrokh; Yaszemski, Michael J.; Chen, Qingshan; An, Kai-Nan; Westendorf, Jennifer J.

    2012-01-01

    Histone deacetylase 3 (Hdac3) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression. Hdac3 interacts with bone-related transcription factors and co-factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system. To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout (CKO) mice were created with the Osteocalcin (OCN) promoter driving Cre expression. Hdac3 CKOOCN mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age. The Hdac3 CKOOCN mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures. Bone resorption was lower, not higher, in the Hdac3 CKOOCN mice, suggesting that primary defects in osteoblasts caused the reduced bone mass. Indeed, reductions in bone formation were observed. Osteoblasts and osteocytes from Hdac3 CKOOCN mice showed increased DNA damage and reduced functional activity in vivo and in vitro. Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging. PMID:23085085

  16. Detection of age-related duplications in mtDNA from human muscles and bones.

    PubMed

    Lacan, Marie; Thèves, Catherine; Keyser, Christine; Farrugia, Audrey; Baraybar, Jose-Pablo; Crubézy, Eric; Ludes, Bertrand

    2011-03-01

    Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification. PMID:20358214

  17. The effect of victim age on burnt bone fragmentation: implications for remains recovery.

    PubMed

    Waterhouse, Kathryn

    2013-09-10

    This research investigates how victim bone age affects the fragmentation and subsequent recovery of burnt bone. It could be inferred that the lower density and higher organic content of bone from younger individuals results in more significant bone breakdown compared to bone from older individuals. Previous research has suggested that while neonate bone can be difficult to destroy in a burn environment it is more fragile post-burning. Results comparing fragmentation of calcined piglet and fattening-pig remains reveal that, while consisting of smaller fragments, the younger material is less fragmented with more complete or almost complete bone elements. These observations have significant implications for remains recovery, especially of younger remains, as it highlights the value of this material as well as the importance of utilising search and recovery strategies that minimise post-burning disturbance. Younger bone responds differently to the burn environment and, therefore; it needs to be taken into consideration when planning remains discovery and retrieval to ensure maximum benefit to the investigation and individuals involved. PMID:23683947

  18. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs.

    PubMed

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  19. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs

    PubMed Central

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  20. Is Greulich and Pyle atlas still a good reference for bone age assessment?

    NASA Astrophysics Data System (ADS)

    Zhang, Aifeng; Tsao, Sinchai; Sayre, James W.; Gertych, Arkadiusz; Liu, Brent J.; Huang, H. K.

    2007-03-01

    The most commonly used method for bone age assessment in clinical practice is the book atlas matching method developed by Greulich and Pyle in the 1950s. Due to changes in both population diversity and nutrition in the United States, this atlas may no longer be a good reference. An updated data set becomes crucial to improve the bone age assessment process. Therefore, a digital hand atlas was built with 1,100 children hand images, along with patient information and radiologists' readings, of normal Caucasian (CAU), African American (BLK), Hispanic (HIS), and Asian (ASI) males (M) and females (F) with ages ranging from 0 - 18 years. This data was collected from Childrens' Hospital Los Angeles. A computer-aided-diagnosis (CAD) method has been developed based on features extracted from phalangeal regions of interest (ROIs) and carpal bone ROIs from this digital hand atlas. Using the data collected along with the Greulich and Pyle Atlas-based readings and CAD results, this paper addresses this question: "Do different ethnicities and gender have different bone growth patterns?" To help with data analysis, a novel web-based visualization tool was developed to demonstrate bone growth diversity amongst differing gender and ethnic groups using data collected from the Digital Atlas. The application effectively demonstrates a discrepancy of bone growth pattern amongst different populations based on race and gender. It also has the capability of helping a radiologist determine the normality of skeletal development of a particular patient by visualizing his or her chronological age, radiologist reading, and CAD assessed bone age relative to the accuracy of the P&G method.

  1. Combined Effects of Spaceflight and Age in Astronauts as Assessed by Areal Bone Mineral Density [BMD] and Trabecular Bone Score

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean D.; Spector, Elizabeth R.; Ploutz-Snyder, R.; Evans, H. J.; King, L.; Watts, N. B.; Hans, D.; Smith, S. A.

    2013-01-01

    Spaceflight is a potential risk factor for secondary osteoporosis in astronauts. Although lumbar spine (LS) BMD declines rapidly, more than expected for age, there have been no fragility fractures in astronauts that can clearly be attributed to spaceflight. Recently, astronauts have been returning from 6-month spaceflights with absolute BMD still above young adult mean BMD. In spite of these BMD measurements, we project that the rapid loss in bone mass over long-duration spaceflight affects the bone microarchitecture of the LS which might predispose astronauts to premature vertebral fractures. Thus, we evaluated TBS, a novel texture index correlated with vertebral bone microarchitecture, as a means of monitoring changes to bone microarchitecture in astronauts as they age. We previously reported that TBS detects an effect of spaceflight (6-month duration), independent of BMD, in 51 astronauts (47+/-4 y) (Smith et al, J Clin Densitometry 2014). Hence, TBS was evaluated in serial DXA scans (Hologic Discovery W) conducted triennially in all active and retired astronauts and more frequently (before spaceflight, after spaceflight and until recovery) in the subset of astronauts flying 4-6- month missions. We used non-linear models to describe trends in observations (BMD or TBS) plotted as a function of astronaut age. We fitted 1175 observations of 311 astronauts, pre-flight and then postflight starting 3 years after landing or after astronaut's BMD for LS was restored to within 2% of preflight BMD. Observations were then grouped and defined as follows: 1) LD: after exposure to at least one long-duration spaceflight > 100 days and 2) SD: before LD and after exposure to at least one short-duration spaceflight < 30 days. Data from males and females were analyzed separately. Models of SD observations revealed that TBS and BMD had similar curvilinear declines with age for both male and female astronauts. However, models of LD observations showed TBS declining with age while

  2. Effects of Resveratrol Supplementation on Bone Growth in Young Rats and Microarchitecture and Remodeling in Ageing Rats

    PubMed Central

    Lee, Alice M. C.; Shandala, Tetyana; Nguyen, Long; Muhlhausler, Beverly S.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

    2014-01-01

    Osteoporosis is a highly prevalent skeletal disorder in the elderly that causes serious bone fractures. Peak bone mass achieved at adolescence has been shown to predict bone mass and osteoporosis related risk fracture later in life. Resveratrol, a natural polyphenol compound, may have the potential to promote bone formation and reduce bone resorption. However, it is unclear whether it can aid bone growth and bone mass accumulation during rapid growth and modulate bone metabolism during ageing. Using rat models, the current study investigated the potential effects of resveratrol supplementation during the rapid postnatal growth period and in late adulthood (early ageing) on bone microarchitecture and metabolism. In the growth trial, 4-week-old male hooded Wistar rats on a normal chow diet were given resveratrol (2.5 mg/kg/day) or vehicle control for 5 weeks. In the ageing trial, 6-month-old male hooded Wistar rats were treated with resveratrol (20 mg/kg/day) or vehicle for 3 months. Treatment effects in the tibia were examined by μ-computer tomography (μ-CT) analysis, bone histomorphometric measurements and reverse transcription-polymerase chain reaction (RT-PCR) gene expression analysis. Resveratrol treatment did not affect trabecular bone volume and bone remodeling indices in the youth animal model. Resveratrol supplementation in the early ageing rats tended to decrease trabecular bone volume, Sirt1 gene expression and increased expression of adipogenesis-related genes in bone, all of which were statistically insignificant. However, it decreased osteocalcin expression (p = 0.03). Furthermore, serum levels of bone resorption marker C-terminal telopeptides type I collagen (CTX-1) were significantly elevated in the resveratrol supplementation group (p = 0.02) with no changes observed in serum levels of bone formation marker alkaline phosphatase (ALP). These results in rat models suggest that resveratrol supplementation does not significantly affect bone volume

  3. Age profiles in elephant and mammoth bone assemblages

    NASA Astrophysics Data System (ADS)

    Haynes, Gary

    1985-11-01

    Age profiles of modern African elephant ( Loxodonta africana) populations are significantly affected by drought conditions that cause local die-offs. Subadult animals die in proportions that may be nearly twice what is recorded in live populations. Such biasing of death sample age profiles might also have occurred during late Pleistocene die-offs of Mammuthus. This comparative study of modern and fossil proboscidean age structures supports a tentative interpretation that late Pleistocene extinction of Mammuthus (at least in the southwestern United States) resulted from severe drought conditions, at which Clovis hunters were witnesses, but not necessarily frequent participants.

  4. Lessons from the Bone Chapter of the Malaysian Aging Men Study.

    PubMed

    Chin, Kok-Yong; Wan Ngah, Wan Zurinah; Ima-Nirwana, Soelaiman

    2016-01-01

    Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009-2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future. PMID:27231930

  5. Lessons from the Bone Chapter of the Malaysian Aging Men Study

    PubMed Central

    Chin, Kok-Yong; Wan Ngah, Wan Zurinah; Ima-Nirwana, Soelaiman

    2016-01-01

    Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009–2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future. PMID:27231930

  6. Effect of aging on the toughness of human cortical bone:Evaluation by R-curves

    SciTech Connect

    Nalla, Ravi K.; Kruzic, Jamie J.; Kinney, John H.; Ritchie,Robert O.

    2005-04-05

    Age-related deterioration of the fracture properties ofbone, coupled with increased life expectancy, is responsible forincreasing incidence of bone fracture in the elderly, and hence, anunderstanding of how its fracture properties degrade with age isessential. The present study describes ex vivo fracture experiments toquantitatively assess the effect of aging on the fracture toughnessproperties of human cortical bone in the longitudinal direction. Becausecortical bone exhibits rising crack-growth resistance with crackextension, unlike most previous studies, the toughness is evaluated interms of resistance-curve (R-curve) behavior, measured for bone takenfrom wide range of age groups (34-99 years). Using this approach, boththe ex vivo crack-initiation and crack-growth toughness are determinedand are found to deteriorate with age; the initiation toughness decreasessome 40 percent over 6 decades from 40 to 100 years, while the growthtoughness is effectively eliminated over the same age range. Thereduction in crack-growth toughness is considered to be associatedprimarily with a degradation in the degree of extrinsic toughening, inparticular, involving crack bridging in the wake of thecrack.

  7. Digital hand atlas for web-based bone age assessment: system design and implementation

    NASA Astrophysics Data System (ADS)

    Cao, Fei; Huang, H. K.; Pietka, Ewa; Gilsanz, Vicente

    2000-04-01

    A frequently used assessment method of skeletal age is atlas matching by a radiological examination of a hand image against a small set of Greulich-Pyle patterns of normal standards. The method however can lead to significant deviation in age assessment, due to a variety of observers with different levels of training. The Greulich-Pyle atlas based on middle upper class white populations in the 1950s, is also not fully applicable for children of today, especially regarding the standard development in other racial groups. In this paper, we present our system design and initial implementation of a digital hand atlas and computer-aided diagnostic (CAD) system for Web-based bone age assessment. The digital atlas will remove the disadvantages of the currently out-of-date one and allow the bone age assessment to be computerized and done conveniently via Web. The system consists of a hand atlas database, a CAD module and a Java-based Web user interface. The atlas database is based on a large set of clinically normal hand images of diverse ethnic groups. The Java-based Web user interface allows users to interact with the hand image database form browsers. Users can use a Web browser to push a clinical hand image to the CAD server for a bone age assessment. Quantitative features on the examined image, which reflect the skeletal maturity, is then extracted and compared with patterns from the atlas database to assess the bone age.

  8. Computer-aided bone age assessment for ethnically diverse older children using integrated fuzzy logic system

    NASA Astrophysics Data System (ADS)

    Ma, Kevin; Moin, Paymann; Zhang, Aifeng; Liu, Brent

    2010-03-01

    Bone Age Assessment (BAA) of children is a clinical procedure frequently performed in pediatric radiology to evaluate the stage of skeletal maturation based on the left hand x-ray radiograph. The current BAA standard in the US is using the Greulich & Pyle (G&P) Hand Atlas, which was developed fifty years ago and was only based on Caucasian population from the Midwest US. To bring the BAA procedure up-to-date with today's population, a Digital Hand Atlas (DHA) consisting of 1400 hand images of normal children of different ethnicities, age, and gender. Based on the DHA and to solve inter- and intra-observer reading discrepancies, an automatic computer-aided bone age assessment system has been developed and tested in clinical environments. The algorithm utilizes features extracted from three regions of interests: phalanges, carpal, and radius. The features are aggregated into a fuzzy logic system, which outputs the calculated bone age. The previous BAA system only uses features from phalanges and carpal, thus BAA result for children over age of 15 is less accurate. In this project, the new radius features are incorporated into the overall BAA system. The bone age results, calculated from the new fuzzy logic system, are compared against radiologists' readings based on G&P atlas, and exhibits an improvement in reading accuracy for older children.

  9. sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss

    PubMed Central

    Haraguchi, Ryuma; Kitazawa, Riko; Mori, Kiyoshi; Tachibana, Ryosuke; Kiyonari, Hiroshi; Imai, Yuuki; Abe, Takaya; Kitazawa, Sohei

    2016-01-01

    sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts, and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling. PMID:27117872

  10. sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss.

    PubMed

    Haraguchi, Ryuma; Kitazawa, Riko; Mori, Kiyoshi; Tachibana, Ryosuke; Kiyonari, Hiroshi; Imai, Yuuki; Abe, Takaya; Kitazawa, Sohei

    2016-01-01

    sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts, and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling. PMID:27117872

  11. Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

    NASA Astrophysics Data System (ADS)

    Dant, James T.; Richardson, Richard B.; Nie, Linda H.

    2013-05-01

    Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient

  12. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

    PubMed Central

    Lyra, Andre Castro; Soares, Milena Botelho Pereira; da Silva, Luiz Flavio Maia; Fortes, Marcos Fraga; Silva, André Goyanna Pinheiro; Mota, Augusto César de Andrade; Oliveira, Sheilla A; Braga, Eduardo Lorens; de Carvalho, Wilson Andrade; Genser, Bernd; dos Santos, Ricardo Ribeiro; Lyra, Luiz Guilherme Costa

    2007-01-01

    AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 ± 0.9) and 4 mo (2.10 ± 1.0) after cell transplantation that baseline levels (2.78 ± 1.2). Albumin levels 4 mo after BMC infusion (3.73 ± 0.5) were higher than baseline levels (3.47 ± 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease. PMID:17373741

  13. Advanced glycation end products (AGEs) and diabetic vascular complications.

    PubMed

    Yamagishi, Sho-ichi; Nakamura, Kazuo; Imaizumi, Tsutomu

    2005-02-01

    Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the development and progression of diabetic micro- and macroangiopathy. Among various metabolic derangements implicated in the pathogenesis of diabetic vascular complication, advanced glycation end product (AGE) hypothesis is most compatible with the theory of 'hyperglycemic memory'. In this review, we discuss the molecular mechanisms of diabetic vascular complication, specially focusing on AGEs and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in this devastating disorder are also discussed here. PMID:18220586

  14. Oxygen isotope analysis of human bone phosphate evidences weaning age in archaeological populations.

    PubMed

    Britton, Kate; Fuller, Benjamin T; Tütken, Thomas; Mays, Simon; Richards, Michael P

    2015-06-01

    Here we report bone phosphate oxygen (δ(18)Op) values from perinates/neonates and infants (<3.5 years; n = 32); children (4-12 years; n = 12); unsexed juveniles (16-18 years; n = 2); and adult bones (n = 17) from Wharram Percy, North Yorkshire, England, in order to explore the potential of this method to investigate patterns of past breastfeeding and weaning. In prior studies, δ(15)N and δ(13)C analyses of bone collagen have been utilized to explore weaning age in this large and well-studied assemblage, rendering this material highly appropriate for the testing and development of this alternative method targeting the inorganic phase of bone. Data produced reveal (18)O-enrichment in the youngest perinatal/neonatal and infant samples, and an association between age and bone δ(18)Op (and previously-published δ(15)N values), with high values in both these isotope systems likely due to breastfeeding. After the age of 2-3 years, δ(18)Op values are lower, and all children between the ages of 4 and 12, along with the vast majority of sub-adults and adults sampled (aged 16 to >50 years), have δ(18)Op values consistent with the consumption of local modern drinking water. The implications of this study for the reconstruction of weaning practices in archaeological populations are discussed, including variations observed with bone δ(15)Ncoll and δ(18)Op co-analysis and the influence of culturally-modified drinking water and seasonality. The use of this method to explore human mobility and palaeoclimatic conditions are also discussed with reference to the data presented. PMID:25677569

  15. Aging and loading rate effects on the mechanical behavior of equine bone

    NASA Astrophysics Data System (ADS)

    Kulin, Robb M.; Jiang, Fengchun; Vecchio, Kenneth S.

    2008-06-01

    Whether due to a sporting accident, high-speed impact, fall, or other catastrophic event, the majority of clinical bone fractures occur under dynamic loading conditions. However, although extensive research has been performed on the quasi-static fracture and mechanical behavior of bone to date, few high-quality studies on the fracture behavior of bone at high strain rates have been performed. Therefore, many questions remain regarding the material behavior, including not only the loading-rate-dependent response of bone, but also how this response varies with age. In this study, tests were performed on equine femoral bone taken post-mortem from donors 6 months to 28 years of age. Quasi-static and dynamic tests were performed to determine the fracture toughness and compressive mechanical behavior as a function of age at varying loading rates. Fracture paths were then analyzed using scanning confocal and scanning-electron microscopy techniques to assess the role of various microstructural features on toughening mechanisms.

  16. Advanced BMP Gene Therapies for Temporal and Spatial Control of Bone Regeneration

    PubMed Central

    Wilson, C.G.; Martín-Saavedra, F.M.; Vilaboa, N.; Franceschi, R.T.

    2013-01-01

    Spatial and temporal patterns of bone morphogenetic protein (BMP) signaling are crucial to the assembly of appropriately positioned and shaped bones of the face and head. This review advances the hypothesis that reconstitution of such patterns with cutting-edge gene therapies will transform the clinical management of craniofacial bone defects attributed to trauma, disease, or surgical resection. Gradients in BMP signaling within developing limbs and orofacial primordia regulate proliferation and differentiation of mesenchymal progenitors. Similarly, vascular and mesenchymal cells express BMPs in various places and at various times during normal fracture healing. In non-healing fractures of long bones, BMP signaling is severely attenuated. Devices that release recombinant BMPs promote healing of bone in spinal fusions and, in some cases, of open fractures, but cannot control the timing and localization of BMP release. Gene therapies with regulated expression systems may provide substantial improvements in efficacy and safety compared with protein-based therapies. Synthetic gene switches, activated by pharmacologics or light or hyperthermic stimuli, provide several avenues for the non-invasive regulation of the expression of BMP transgenes in both time and space. Through new gene therapy platforms such as these, active control over BMP signaling can be achieved to accelerate bone regeneration. PMID:23539558

  17. Simulated Interventions to Ameliorate Age-Related Bone Loss Indicate the Importance of Timing.

    PubMed

    Proctor, Carole J; Gartland, Alison

    2016-01-01

    Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order to maintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt, parathyroid hormone (PTH), RANK ligand/osteoprotegrin, and TGF-β, in response to stimuli, such as mechanical loading. During aging there is a gradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with age and/or changes in hormones and other signaling molecules. In particular, hormones, such as PTH, have a circadian rhythm, which may be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, several mathematical models have been proposed to aid understanding of the processes involved. However, to date, there are no models, which explicitly consider the effects of mechanical loading, the circadian rhythm of PTH, and the dynamics of signaling molecules on bone remodeling. Therefore, we have constructed a network model of the system using a modular approach, which will allow further modifications as required in future research. The model was used to simulate the effects of mechanical loading and also the effects of different interventions, such as continuous or intermittent administration of PTH. Our model predicts that the absence of regular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time, which can be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing. PMID:27379013

  18. Simulated Interventions to Ameliorate Age-Related Bone Loss Indicate the Importance of Timing

    PubMed Central

    Proctor, Carole J.; Gartland, Alison

    2016-01-01

    Bone remodeling is the continuous process of bone resorption by osteoclasts and bone formation by osteoblasts, in order to maintain homeostasis. The activity of osteoclasts and osteoblasts is regulated by a network of signaling pathways, including Wnt, parathyroid hormone (PTH), RANK ligand/osteoprotegrin, and TGF-β, in response to stimuli, such as mechanical loading. During aging there is a gradual loss of bone mass due to dysregulation of signaling pathways. This may be due to a decline in physical activity with age and/or changes in hormones and other signaling molecules. In particular, hormones, such as PTH, have a circadian rhythm, which may be disrupted in aging. Due to the complexity of the molecular and cellular networks involved in bone remodeling, several mathematical models have been proposed to aid understanding of the processes involved. However, to date, there are no models, which explicitly consider the effects of mechanical loading, the circadian rhythm of PTH, and the dynamics of signaling molecules on bone remodeling. Therefore, we have constructed a network model of the system using a modular approach, which will allow further modifications as required in future research. The model was used to simulate the effects of mechanical loading and also the effects of different interventions, such as continuous or intermittent administration of PTH. Our model predicts that the absence of regular mechanical loading and/or an impaired PTH circadian rhythm leads to a gradual decrease in bone mass over time, which can be restored by simulated interventions and that the effectiveness of some interventions may depend on their timing. PMID:27379013

  19. Cyclophilin D Knock-Out Mice Show Enhanced Resistance to Osteoporosis and to Metabolic Changes Observed in Aging Bone

    PubMed Central

    White, Noelle S; Nadtochiy, Sergiy M.; Bentley, Karen L. de Mesy; Brookes, Paul S; Jonason, Jennifer H.; Eliseev, Roman A.

    2016-01-01

    Pathogenic factors associated with aging, such as oxidative stress and hormone depletion converge on mitochondria and impair their function via opening of the mitochondrial permeability transition pore (MPTP). The MPTP is a large non-selective pore regulated by cyclophilin D (CypD) that disrupts mitochondrial membrane integrity. MPTP involvement has been firmly established in degenerative processes in heart, brain, and muscle. Bone has high energy demands and is therefore expected to be highly sensitive to mitochondrial dysfunction. Despite this, the role of mitochondria and the MPTP in bone maintenance and bone pathology has not been elucidated. Our goal was to determine whether mitochondria are impaired in aging bone and to see if protecting mitochondria from MPTP opening via CypD deletion protects against bone loss. We found that bone mass, strength, and formation progressively decline over the course of 18 months in C57BL/6J mice. Using metabolomics and electron microscopy, we determined that oxidative metabolism is impaired in aging bone leading to a glycolytic shift, imbalance in nucleotides, and decreased NAD+/NADH ratio. Mitochondria in osteocytes appear swollen which is a major marker of MPTP opening. CypD deletion by CypD knockout mouse model (CypD KO) protects against bone loss in 13- and 18-month-old mice and prevents decline in bone formation and mitochondrial changes observed in wild type C57BL/6J mice. Together, these data demonstrate that mitochondria are impaired in aging bone and that CypD deletion protects against this impairment to prevent bone loss. This implicates CypD-regulated MPTP and mitochondrial dysfunction in the impairment of bone cells and in aging-related bone loss. Our findings suggest mitochondrial metabolism as a new target for bone therapeutics and inhibition of CypD as a novel strategy against bone loss. PMID:27183225

  20. Avalanche criticality during compression of porcine cortical bone of different ages.

    PubMed

    Baró, Jordi; Shyu, Peter; Pang, Siyuan; Jasiuk, Iwona M; Vives, Eduard; Salje, Ekhard K H; Planes, Antoni

    2016-05-01

    Crack events developed during uniaxial compression of cortical bones cut from femurs of developing pigs of several ages (4, 12, and 20 weeks) generate avalanches. These avalanches have been investigated by acoustic emission analysis techniques. The avalanche energies are power-law distributed over more than four decades. Such behavior indicates the absence of characteristic scales and suggests avalanche criticality. The statistical distributions of energies and waiting times depend on the pig age and indicate that bones become stronger, but less ductile, with increasing age. Crack propagation is equally age-dependent. Older pigs show, on average, larger cracks with a time distribution similar to those of aftershocks in earthquakes, while younger pigs show only statistically independent failure events. PMID:27300967

  1. Avalanche criticality during compression of porcine cortical bone of different ages

    NASA Astrophysics Data System (ADS)

    Baró, Jordi; Shyu, Peter; Pang, Siyuan; Jasiuk, Iwona M.; Vives, Eduard; Salje, Ekhard K. H.; Planes, Antoni

    2016-05-01

    Crack events developed during uniaxial compression of cortical bones cut from femurs of developing pigs of several ages (4, 12, and 20 weeks) generate avalanches. These avalanches have been investigated by acoustic emission analysis techniques. The avalanche energies are power-law distributed over more than four decades. Such behavior indicates the absence of characteristic scales and suggests avalanche criticality. The statistical distributions of energies and waiting times depend on the pig age and indicate that bones become stronger, but less ductile, with increasing age. Crack propagation is equally age-dependent. Older pigs show, on average, larger cracks with a time distribution similar to those of aftershocks in earthquakes, while younger pigs show only statistically independent failure events.

  2. The application of cone-beam CT in the aging of bone calluses: a new perspective?

    PubMed

    Cappella, A; Amadasi, A; Gaudio, D; Gibelli, D; Borgonovo, S; Di Giancamillo, M; Cattaneo, C

    2013-11-01

    In the forensic and anthropological fields, the assessment of the age of a bone callus can be crucial for a correct analysis of injuries in the skeleton. To our knowledge, the studies which have focused on this topic are mainly clinical and still leave much to be desired for forensic purposes, particularly in looking for better methods for aging calluses in view of criminalistic applications. This study aims at evaluating the aid cone-beam CT can give in the investigation of the inner structure of fractures and calluses, thus acquiring a better knowledge of the process of bone remodeling. A total of 13 fractures (three without callus formation and ten with visible callus) of known age from cadavers were subjected to radiological investigations with digital radiography (DR) (conventional radiography) and cone-beam CT with the major aim of investigating the differences between DR and tomographic images when studying the inner and outer structures of bone healing. Results showed how with cone-beam CT the structure of the callus is clearly visible with higher specificity and definition and much more information on mineralization in different sections and planes. These results could lay the foundation for new perspectives on bone callus evaluation and aging with cone-beam CT, a user-friendly and skillful technique which in some instances can also be used extensively on the living (e.g., in cases of child abuse) with reduced exposition to radiation. PMID:23389391

  3. Interaction of Age and Mechanical Stability on Bone Defect Healing: An Early Transcriptional Analysis of Fracture Hematoma in Rat

    PubMed Central

    Ode, Andrea; Duda, Georg N.; Geissler, Sven; Pauly, Stephan; Ode, Jan-Erik; Perka, Carsten; Strube, Patrick

    2014-01-01

    Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging) and external fixator stiffness (mechanically challenging). From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability) in combination rather than alone. PMID:25187955

  4. [Neutrophilic dermatosis in ulcerative colitis occurring in advanced age].

    PubMed

    López Maldonado, M D; Calvo Catalá, J; Ronda Gasulla, A; Hortelano Martínez, E; Herrera Ballester, A; Febrer Bosch, I

    1994-08-01

    The Neutrophilic dermatosis (ND) is considered as an independent entity with diverse clinical manifestations among which there are: gangrenous pyoderma, nodous erythema, Sweets Syndrome, vesiculopustula eruptions associated to ulcerous colitis and intestinal short circuit syndrome with or without short circuit. Histologically, they are characterized by infiltration of polymorphonuclear neutrophils, generally at the dermic level, but also at the epidermic. They are usually associated to systemic diseases, especially to chronic intestinal inflammatory disease. Our aim was to describe two forms of clinical presentation of neutrophilic dermatosis: gangrenous pyoderma and vesiculopustula eruption, associated to ulcerous colitis starting at advances ages. PMID:7772690

  5. The dependences of osteocyte network on bone compartment, age, and disease

    PubMed Central

    Lai, Xiaohan; Price, Christopher; Modla, Shannon; Thompson, William R; Caplan, Jeffrey; Kirn-Safran, Catherine B; Wang, Liyun

    2015-01-01

    Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system (LCS) buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood supply, sense external mechanical signals, and communicate among themselves and with other cells on bone surfaces. In this study, we examined key features of the LCS network including the topological parameter and the detailed structure of individual connections and their variations in cortical and cancellous compartments, at different ages, and in two disease conditions with altered mechanosensing (perlecan deficiency and diabetes). LCS network showed both topological stability, in terms of conservation of connectivity among osteocyte lacunae (similar to the “nodes” in a computer network), and considerable variability the pericellular annular fluid gap surrounding lacunae and canaliculi (similar to the “bandwidth” of individual links in a computer network). Age, in the range of our study (15–32 weeks), affected only the pericellular fluid annulus in cortical bone but not in cancellous bone. Diabetes impacted the spacing of the lacunae, while the perlecan deficiency had a profound influence on the pericellular fluid annulus. The LCS network features play important roles in osteocyte signaling and regulation of bone growth and adaptation. PMID:26213632

  6. Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

    PubMed

    Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

    2016-08-01

    This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline. PMID:27108136

  7. Lessons from Microglia Aging for the Link between Inflammatory Bone Disorders and Alzheimer's Disease

    PubMed Central

    Nakanishi, Hiroshi

    2015-01-01

    Bone is sensitive to overactive immune responses, which initiate the onset of inflammatory bone disorders, such as rheumatoid arthritis and periodontitis, resulting in a significant systemic inflammatory response. On the other hand, neuroinflammation is strongly implicated in Alzheimer's disease (AD), which can be enhanced by systemic inflammation, such as that due to cardiovascular disease and diabetes. There is growing clinical evidence supporting the concept that rheumatoid arthritis and periodontitis are positively linked to AD, suggesting that inflammatory bone disorders are risk factors for this condition. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to brain-resident microglia. More importantly, senescent-type, but not juvenile-type, microglia provoke neuroinflammation in response to systemic inflammation. Because the prevalence of rheumatoid arthritis and periodontitis increases with age, inflammatory bone disorders may be significant sources of covert systemic inflammation among elderly people. The present review article highlights our current understanding of the link between inflammatory bone disorders and AD with a special focus on microglia aging. PMID:26078980

  8. Evaluation of bone remodeling in regard to the age of scaphoid non-unions

    PubMed Central

    Rein, Susanne; Hanisch, Uwe; Schaller, Hans-Eberhard; Zwipp, Hans; Rammelt, Stefan; Weindel, Stefan

    2016-01-01

    AIM: To analyse bone remodeling in regard to the age of scaphoid non-unions (SNU) with immunohistochemistry. METHODS: Thirty-six patients with symptomatic SNU underwent surgery with resection of the pseudarthrosis. The resected material was evaluated histologically after staining with hematoxylin-eosin (HE), tartrate resistant acid phosphatase (TRAP), CD 68, osteocalcin (OC) and osteopontin (OP). Histological examination was performed in a blinded fashion. RESULTS: The number of multinuclear osteoclasts in the TRAP-staining correlated with the age of the SNU and was significantly higher in younger SNU (P = 0.034; r = 0.75). A higher number of OP-immunoreactive osteoblasts significantly correlated with a higher number of OC-immunoreactive osteoblasts (P = 0.001; r = 0.55). Furthermore, a greater number of OP-immunoreactive osteoblasts correlated significantly with a higher number of OP-immunoreactive multinuclear osteoclasts (P = 0.008; r = 0.43). SNU older than 6 mo showed a significant decrease of the number of fibroblasts (P = 0.04). Smoking and the age of the patients had no influence on bone remodeling in SNU. CONCLUSION: Multinuclear osteoclasts showed a significant decrease in relation to the age of SNU. However, most of the immunhistochemical findings of bone remodeling do not correlate with the age of the SNU. This indicates a permanent imbalance of bone formation and resorption as indicated by a concurrent increase in both osteoblast and osteoclast numbers. A clear histological differentiation into phases of bone remodeling in SNU is not possible. PMID:27458552

  9. Sexuality in advanced age in Jewish thought and law.

    PubMed

    David, Benjamin E; Weitzman, Gideon A

    2015-01-01

    Judaism has a positive attitude to sexual relations within a marriage, and views such sexual relations as important not only for procreation but also as part of the framework of marriage. This is true for any age group, and sexuality is seen as an essential element of marriage for couples of advanced age. In this article, the authors present the views of Jewish law and thought regarding sexuality among older couples. The authors illustrate this using 3 case studies of couples who sought guidance in the area of sexuality. In addition, this area of counseling benefits greatly from an ongoing relationship and dialogue between expert rabbis in the field and therapists treating older Orthodox Jewish patients for sexual dysfunction. The triad relationship of couple, therapist, and rabbi enhances the ability to treat and assist such couples to seek treatment and overcome their difficulties. PMID:24313599

  10. Mesenchymal Stem Cells Ageing: Targeting the "Purinome" to Promote Osteogenic Differentiation and Bone Repair.

    PubMed

    Noronha-Matos, J B; Correia-de-Sá, P

    2016-09-01

    Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming cells. Such ability is compromised in elderly individuals resulting in bone disorders such as osteoporosis, also limiting their clinical usage for cell transplantation and bone tissue engineering strategies. In bone marrow niches, adenine and uracil nucleotides are important local regulators of osteogenic differentiation of MSCs. Nucleotides can be released to the extracellular milieu under both physiological and pathological conditions via (1) membrane cell damage, (2) vesicle exocytosis, (3) ATP-binding cassette transporters, and/or (4) facilitated diffusion through maxi-anion channels, hemichannels or ligand-gated receptor pores. Nucleotides and their derivatives act via adenosine P1 (A1 , A2A , A2B , and A3 ) and nucleotide-sensitive P2 purinoceptors comprising ionotropic P2X and G-protein-coupled P2Y receptors. Purinoceptors activation is terminated by membrane-bound ecto-nucleotidases and other ecto-phosphatases, which rapidly hydrolyse extracellular nucleotides to their respective nucleoside 5'-di- and mono-phosphates, nucleosides and free phosphates, or pyrophosphates. Current knowledge suggests that different players of the "purinome" cascade, namely nucleotide release sites, ecto-nucleotidases and purinoceptors, orchestrate to fine-tuning regulate the activity of MSCs in the bone microenvironment. Increasing studies, using osteoprogenitor cell lines, animal models and, more recently, non-modified MSCs from postmenopausal women, raised the possibility to target chief components of the purinergic signaling pathway to regenerate the ability of aged MSCs to differentiate into functional osteoblasts. This review summarizes the main findings of those studies, prompting for novel therapeutic strategies to control ageing disorders where bone destruction exceeds bone formation, like osteoporosis, rheumatoid arthritis, and fracture mal-union. J. Cell. Physiol. 231: 1852

  11. Ages of fossil bones from British interglacial sites

    USGS Publications Warehouse

    Szabo, B. J.; Collins, D.

    1975-01-01

    THE time gap between the upper limit of radiocarbon dating (???60,000 yr BP) and the lower limit of dates generally obtainable using the K-Ar method (???250,000 yr BP) accounts for the scarcity of dates for the last two interglaciations (the Ipswichian and Hoxnian of Britain; the Eemian and Holsteinian of northern Europe). Accordingly, the ages of such important fossils as the Swanscombe and Steinheim skulls can only be guessed at. For that reason, the adaptation of a method that may date these interglacial periods is highly desirable. We discuss here the application of a uranium-series dating technique pertaining to that span of time. ?? 1975 Nature Publishing Group.

  12. Age-specific profiles of tissue-level composition and mechanical properties in murine cortical bone

    PubMed Central

    Raghavan, Mekhala; Sahar, Nadder D.; Kohn, David H.; Morris, Michael D.

    2012-01-01

    There is growing evidence that bone composition and tissue-level mechanical properties are significant determinants of skeletal integrity. In the current study, Raman spectroscopy and nanoindentation testing were co-localized to analyze tissue-level compositional and mechanical properties in skeletally mature young (4 or 5 months) and old (19 months) murine femora at similar spatial scales. Standard multivariate linear regression analysis revealed age-dependent patterns in the relationships between mechanical and compositional properties at the tissue scale. However, changes in bone material properties with age are often complex and nonlinear, and can be missed with linear regression and correlation-based methods. A retrospective data mining approach was implemented using non-linear multidimensional visualization and classification to identify spectroscopic and nanoindentation metrics that best discriminated bone specimens of different age-classes. The ability to classify the specimens into the correct age group increased by using combinations of Raman and nanoindentation variables (86–96% accuracy) as compared to using individual measures (59–79% accuracy). Metrics that best classified 4 or 5 month and 19 month specimens (2-age classes) were mineral to matrix ratio, crystallinity, modulus and plasticity index. Metrics that best distinguished between 4, 5 and 19 month specimens (3-age classes) were mineral to matrix ratio, crystallinity, modulus, hardness, cross-linking, carbonate to phosphate ratio, creep displacement and creep viscosity. These findings attest to the complexity of mechanisms underlying bone tissue properties and draw attention to the importance of considering non-linear interactions between tissue-level composition and mechanics that may work together to influence material properties with age. The results demonstrate that a few non-linearly combined compositional and mechanical metrics provide better discriminatory information than a single

  13. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    PubMed

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover. PMID:26487675

  14. Effect of deproteination on bone mineral morphology: implications for biomaterials and aging.

    PubMed

    Carter, D H; Scully, A J; Heaton, D A; Young, M P J; Aaron, J E

    2002-09-01

    Bone mineral morphology is altered by processing and this is rarely considered when preparing bone as a bioimplant material. To examine the degree of transformation, a commercial, coarsely particulate bone mineral biomaterial produced by prolonged deproteination, defatting, dehydration, and heating (donor material) was compared with similar particles of human bone (recipient material) prepared optimally by low-temperature milling. The two powders were freeze-substituted and embedded without thawing in Lowicryl K4M before sectioning for transmission electron microscopy (TEM) (other aliquots were processed by traditional TEM methods). To maximize resolution, electron micrographs were image-enhanced by digitization and printed as negatives using a Polaroid Sprint Scan 45. In addition to their morphology, the particles were examined for antigenicity (specific by reference to fluorescein isothiocyanate [FITC]-conjugated fibronectin, and nonspecific by reference to general FITC-conjugated immunoglobulins). Results showed that the optimally prepared human bone fragments stained discretely for fibronectin with negligible background autofluorescence. In contrast, the bioimplant fragments stained extensively with this and any other FITC-conjugated antibody and, unlike fresh bone, it also autofluoresced a uniform yellow. This difference was also expressed structurally and, although the bioimplant mineral consisted of rhomboidal plates up to 200 nm across and 10 nm thick, the optimally prepared bone mineral was composed of numerous clusters of 5-nm-wide sinuous calcified filaments of variable density and indeterminate length (which became straight needles 50 nm long and 5 nm thick following traditional chemical TEM fixation/staining). It was concluded that the inorganic phase of bone is both morphologically and immunologically transmutable and that, in biomaterials, the transformation is apparently so great that a broad indigenous antigenicity is unmasked, increasing the

  15. Definition of advanced age in HIV infection: looking for an age cut-off.

    PubMed

    Blanco, José R; Jarrín, Inmaculada; Vallejo, Manuel; Berenguer, Juan; Solera, Carmen; Rubio, Rafael; Pulido, Federico; Asensi, Victor; del Amo, Julia; Moreno, Santiago

    2012-09-01

    The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50-54, 55-59, 60-64, 65-59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52-0.87), 29% (aHR: 0.71, 95% CI: 0.53-0.96), 34% (aHR: 0.66, 95% CI: 0.46-0.95), 39% (aHR: 0.61, 95% CI: 0.37-1.00), and 43% (aHR: 0.57, 95% CI: 0.31-1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50-59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07-11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people. PMID:22607516

  16. Definition of Advanced Age in HIV Infection: Looking for an Age Cut-Off

    PubMed Central

    Jarrín, Inmaculada; Vallejo, Manuel; Berenguer, Juan; Solera, Carmen; Rubio, Rafael; Pulido, Federico; Asensi, Victor; del Amo, Julia; Moreno, Santiago

    2012-01-01

    Abstract The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50–54, 55–59, 60–64, 65–59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52–0.87), 29% (aHR: 0.71, 95% CI: 0.53–0.96), 34% (aHR: 0.66, 95% CI: 0.46–0.95), 39% (aHR: 0.61, 95% CI: 0.37–1.00), and 43% (aHR: 0.57, 95% CI: 0.31–1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50–59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07–11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people. PMID:22607516

  17. Aged Male Rats Regenerate Cortical Bone with Reduced Osteocyte Density and Reduced Secretion of Nitric Oxide After Mechanical Stimulation

    PubMed Central

    Tayim, Riyad J.; McElderry, John-David; Morris, Michael D.; Goldstein, Steven A.

    2016-01-01

    Mechanical loading is integral to the repair of bone damage. Osteocytes are mechanosensors in bone and participate in signaling through gap junction channels, which are primarily comprised of connexin 43 (Cx43). Nitric oxide (NO) and prostaglandin E2 (PGE2) have anabolic and catabolic effects on bone, and the secretion of these molecules occurs after mechanical stimulation. The effect of age on the repair of bone tissue after damage and on the ability of regenerated bone to transduce mechanical stimulation into a cellular response is unexplored. The goal of this study was to examine (1) osteocytes and their mineralized matrix within regenerated bone from aged and mature animals and (2) the ability of regenerated bone explants from aged and mature animals to transduce cyclic mechanical loading into a cellular response through NO and PGE2 secretion. Bilateral cortical defects were created in the diaphysis of aged (21-month-old) or mature (6-month-old) male rats, and new bone tissue was allowed to grow into a custom implant of controlled geometry. Mineralization and mineral-to-matrix ratio were significantly higher in regenerated bone from aged animals, while lacunar and osteocyte density and phosphorylated (pCx43) and total Cx43 protein were significantly lower, relative to mature animals. Regenerated bone from mature rats had increased pCx43 protein and PGE2 secretion with loading and greater NO secretion relative to aged animals. Reduced osteocyte density and Cx43 in regenerated bone in aged animals could limit the establishment of gap junctions as well as NO and PGE2 secretion after loading, thereby altering bone formation and resorption in vivo. PMID:24370615

  18. Investigation of the effects of aging on homologous recombination in long-term bone marrow cultures.

    PubMed

    Epperly, Michael W; Rugo, Rebecca; Cao, Shaonan; Wang, Hong; Franicola, Darcy; Goff, Julie P; Shen, Hongmei; Zhang, Xichen; Wiktor-Brown, Dominika; Engelward, Bevin P; Greenberger, Joel S

    2009-01-01

    Fluorescent yellow direct repeat (FYDR) mice carry a transgenic reporter for homologous recombination (HR) and have been used to reveal an age-dependent increase in HR in the pancreas. An established in vitro model system for accelerated aging of the marrow is the mouse long-term bone marrow culture (LTBMC) system. To determine whether the FYDR system, in which an HR event can lead to a fluorescent cell, can be used to study the effects of aging in LTBMCs, clonally expanded hematopoietic and marrow stromal cells in FYDR, positive control FYDR-Recombined (FYDR-Rec), and negative control wild-type C57BL/6NHsd (WT) LTBMCs were analysed. All groups of cultures demonstrated equivalent parameters of continuous hematopoiesis including generation of multilineage colony forming CFU-GM progenitor cells for over 22 weeks and age associated senescence of hematopoiesis. Results indicate that low expression of the FYDR transgene in bone marrow cells in vivo and in vitro prevents the use of the FYDR mice to study rare combination events in bone marrow. Using an alternative approach for detecting HR, namely the sister chromatid exchange (SCE) assay, a statistically significant increase in the number of SCEs per chromosome was observed in adherent cells subcultured from 20-week-compared to 4-week-old LTBMCs. These data suggest that adherent marrow stromal cells from LTBMCs become increasingly susceptible to HR events during aging. PMID:19779099

  19. AGE-RELATED EFFECT ON THE CONCENTRATION OF COLLAGEN CROSSLINKS IN HUMAN OSTEONAL AND INTERSTITIAL BONE TISSUE

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Acuna, Rae L.; Gayle, Heather J.; Reyes, Michael J.; Tyler, Jerrod H.; Dean, David D.; Wang, Xiaodu

    2007-01-01

    Collagen crosslinks are important to the quality of bone and may be contributors to the age-related increase in bone fracture. This study was performed to investigate whether age and gender effects on collagen crosslinks are similar in osteonal and interstitial bone tissues. Forty human cadaveric femurs were collected and divided into two age groups: Middle aged (42–63 years of age) and Elderly (69–90 years of age) with ten males and ten females in each group (n = 10). Micro-cores of bone tissue from both secondary osteons (newly formed) and interstitial regions (biologically old) in the medial quadrant of the diaphysis were extracted using a custom-modified, computer numerical controlled machine. The bone specimens were then analyzed using high performance liquid chromatography to determine the effects of age and gender on the concentration of mature, enzymatic crosslinks (hydroxylysyl-pyridinoline – HP and lysylpyridinoline – LP) and a non-enzymatic crosslink (pentosidine – PE) at these two bony sites. The results indicate that age has a significant effect on the concentration of LP and PE, while gender has a significant effect on HP and LP. In addition, the concentration of the crosslinks in the secondary osteons is significantly different from that in the interstitial bone regions. These results suggest that the rate of non-enzymatic crosslinking may increase while the formation of maturate enzymatic crosslinks may decrease with age. Such changes could potentially reduce the inherent quality of the bone tissue in the elderly skeleton. PMID:16962838

  20. Progressive post-yield behavior of human cortical bone in compression for middle-aged and elderly groups

    PubMed Central

    Leng, Huijie; Dong, X. Neil; Wang, Xiaodu

    2010-01-01

    In this study, a progressive loading regimen (load–dwell–unloading–dwell–reloading) was applied on bone samples to examine the compressive post-yield response of bone at increasing strain levels. Cortical bone specimens from human tibiae of two age groups (middle-aged group: 53±2 years, 4 females and 4 males, elderly group: 83±6 years, 4 females and 4 males) were loaded in compression using the progressive loading scheme. Modulus degradation, plastic deformation, viscous response, and energy dissipation of bone during post-yield deformation were assessed. Although initial modulus was not significantly different between the two age groups, the degradation of modulus with the applied strain in the elderly group was faster than in the middle-aged group. The modulus loss (or microdamage accumulation) of bone occurred prior to plastic deformation. Plastic strain had a similar linear relationship with the applied strain for both middle-aged and the elderly group although middle-aged bone yielded at a greater strain. The viscoelastic time constant changed similarly with increasing strain for the two groups, whereas a higher magnitude of stress relaxation was observed in the middle-aged group. Energy dissipation was investigated through three pathways: elastic release strain energy, hysteresis energy, and plastic strain energy. The middle-aged group had significantly greater capacity of energy dissipation than the elderly group in all three pathways. The information obtained may provide important insights in age-related effects on bone fragility. PMID:19150716

  1. Bone deformities and skeletal malformations in the Roman Imperial Age.

    PubMed

    Minozzi, Simona; Catalano, Paola; Pantano, Walter; Caldarini, Carla; Fornaciari, Gino

    2014-01-01

    This paper describes some cases of individuals affected by skeletal deformities resulting in "freak" appearance. The skeletal remains were found during large archaeological excavations in the Roman territory, carried out by the Special Superintendence to the Archeological Heritage of Rome in the last years, dated back to the Imperial Age. The first cases reported are referred to two growth disorders with opposite effects: a case of dwarfism and another of gigantism. The former concerns a young man from the Collatina necropolis with very short and malformed limbs, which allowed a diagnosis of acondroplasic dwarfism, a rare congenital disorder that limits height below 130 cm. The latter case comes from the necropolis of Torre Serpentana in Fidenae, and is instead referred to a young person of very high stature, about 204 cm, suffering from Gigantism, a rare condition which in this case seems to have been linked to a hormonal dysfunction due to a pituitary adenoma. A third case regards a joint disease affecting the vertebral column and causing severe deformities. The skeleton was found in the Collatina necropolis and belongs to an old woman, suffering from ankylosing spondylitis. Finally, the last and very peculiar case is related to an individual recovered in the necropolis of Castel Malnome. The skeletal remains belong to an adult man with a complete fusion of the temporo-mandibular joint, which compromised mastication and caused severe deformation of the maxillofacial complex. These cases are described in detail together with the possible implications that these deformities could have on in the social context. PMID:25702379

  2. Comprehensive analyses of how tubule occlusion and advanced glycation end-products diminish strength of aged dentin

    PubMed Central

    Shinno, Yuko; Ishimoto, Takuya; Saito, Mitsuru; Uemura, Reo; Arino, Masumi; Marumo, Keishi; Nakano, Takayoshi; Hayashi, Mikako

    2016-01-01

    In clinical dentistry, since fracture is a major cause of tooth loss, better understanding of mechanical properties of teeth structures is important. Dentin, the major hard tissue of teeth, has similar composition to bone. In this study, we investigated the mechanical properties of human dentin not only in terms of mineral density but also using structural and quality parameters as recently accepted in evaluating bone strength. Aged crown and root dentin (age ≥ 40) exhibited significantly lower flexural strength and toughness than young dentin (age < 40). Aged dentin, in which the dentinal tubules were occluded with calcified material, recorded the highest mineral density; but showed significantly lower flexural strength than young dentin. Dentin with strong alignment of the c-axis in hydroxyapatite exhibited high fracture strength, possibly because the aligned apatite along the collagen fibrils may reinforce the intertubular dentin. Aged dentin, showing a high advanced glycation end-products (AGEs) level in its collagen, recorded low flexural strength. We first comprehensively identified significant factors, which affected the inferior mechanical properties of aged dentin. The low mechanical strength of aged dentin is caused by the high mineral density resulting from occlusion of dentinal tubules and accumulation of AGEs in dentin collagen. PMID:26797297

  3. Improvements in IVF in women of advanced age.

    PubMed

    Gleicher, Norbert; Kushnir, Vitaly A; Albertini, David F; Barad, David H

    2016-07-01

    Women above age 40 years in the US now represent the most rapidly growing age group having children. Patients undergoing in vitro fertilization (IVF) are rapidly aging in parallel. Especially where egg donations are legal, donation cycles, therefore, multiply more rapidly than autologous IVF cycles. The donor oocytes, however, are hardly ever a preferred patient choice. Since with use of own eggs, live birth rates decline with advancing age but remain stable (and higher) with donor eggs, older patients always face the difficult and very personal choice between poorer chances with own and better chances with donor oocytes. Physician contribution to this decision should in our opinion be restricted to accurate outcome information for both options. Achievable pregnancy and live birth rates in older women are, however, frequently underestimated, thereby mistakenly biasing fertility providers, private insurance companies and even regulatory government agencies. Restriction on access to IVF for older women is then often the consequence. In this review, we summarize the limited published data on best treatments of 'older' ovaries, while also addressing treatment approaches that should be avoided in older women. This focused review, therefore, to a degree is subjective. Research addressing aging ovaries in IVF has been disappointingly sparse, and has in our opinion too heavily concentrated on methods of embryo selection (ES), which, especially in older women, not only fail to improve IVF outcomes, but actually, negatively affect live birth chances. We conclude that, aside from breakthroughs in gamete creation, only pharmacological interventions into early (small growing follicle stages) follicle maturation will offer new potential to positively impact oocyte and embryo quality and, therefore, IVF outcomes. Research, therefore, should be accordingly redirected. PMID:27154334

  4. Informational Theory of Aging: The Life Extension Method Based on the Bone Marrow Transplantation

    PubMed Central

    Karnaukhov, Alexey V.; Karnaukhova, Elena V.; Sergievich, Larisa A.; Karnaukhova, Natalia A.; Bogdanenko, Elena V.; Manokhina, Irina A.; Karnaukhov, Valery N.

    2015-01-01

    The method of lifespan extension that is a practical application of the informational theory of aging is proposed. In this theory, the degradation (error accumulation) of the genetic information in cells is considered a main cause of aging. According to it, our method is based on the transplantation of genetically identical (or similar) stem cells with the lower number of genomic errors to the old recipients. For humans and large mammals, this method can be realized by cryopreservation of their own stem cells, taken in a young age, for the later autologous transplantation in old age. To test this method experimentally, we chose laboratory animals of relatively short lifespan (mouse). Because it is difficult to isolate the required amount of the stem cells (e.g., bone marrow) without significant damage for animals, we used the bone marrow transplantation from sacrificed inbred young donors. It is shown that the lifespan extension of recipients depends on level of their genetic similarity (syngeneity) with donors. We have achieved the lifespan increase of the experimental mice by 34% when the transplantation of the bone marrow with high level of genetic similarity was used. PMID:26491435

  5. Feasibility of Using a Bone-Targeted, Macromolecular Delivery System Coupled with Prostaglandin E1 to Promote Bone Formation in Aged, Estrogen-Deficient Rats

    PubMed Central

    Miller, S. C.; Pan, H.; Wang, D.; Bowman, B. M.; Kopečková, P.; Kopeček, J.

    2009-01-01

    Purpose Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer–Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods The uptake of FITC-labeled HPMA copolymer–Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions HPMA copolymers can be targeted to bone surfaces using Asp8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases. PMID:18758923

  6. A method for estimating age of Danish medieval sub-adults based on long bone length.

    PubMed

    Primeau, Charlotte; Friis, Laila; Sejrsen, Birgitte; Lynnerup, Niels

    2012-07-01

    The preferred method for aging archaeological sub-adult skeletons is by dental examination. In cases where no dental records are available, age estimation may be performed according to epiphyseal union, skeletal elements or diaphyseal lengths. Currently no data have been produced specifically for aging archaeological Danish sub-adults from the medieval period based on diaphyseal lengths. The problem with using data on Danish samples, which have been derived from a different population, is the possibility of skewing age estimates. In this study 58 Danish archaeological sub-adults were examined, aged from approximately six years to twenty-one years. The samples were aged according to two dental methods: Haavikko and Ubelaker. Regression formulae were constructed for aging according to their diaphyseal lengths both for individual long bones and combinations of upper and lower long bones. This study indicated that with the regression formulae developed, estimation of age can be done with reasonable results on Danish sub-adults. The Danish data were then compared to data from a different archaeological sample and a modern sample. It showed that the modern data indicated a consistently lower age compared to this sample which increased until reaching a maximum of nearly five years and six months. When comparing the archaeological data to this study, the growth profile crossed over at 12.5 years with a maximum age difference before the cross point of two years and three months lower for the archaeological data. After the cross point there was a maximum difference of three years and four months higher for the archaeological data. This study has shown the importance of using data for age estimation for archaeological material which has been developed specifically for that population. In addition it has presented a possible solution for Danish sub-adult material when dental material is not available. PMID:22928354

  7. Bone age assessment by content-based image retrieval and case-based reasoning

    NASA Astrophysics Data System (ADS)

    Fischer, Benedikt; Welter, Petra; Grouls, Christoph; Günther, Rolf W.; Deserno, Thomas M.

    2011-03-01

    Skeletal maturity is assessed visually by comparing hand radiographs to a standardized reference image atlas. Most common are the methods by Greulich & Pyle and Tanner & Whitehouse. For computer-aided diagnosis (CAD), local image regions of interest (ROI) such as the epiphysis or the carpal areas are extracted and evaluated. Heuristic approaches trying to automatically extract, measure and classify bones and distances between bones suffer from the high variability of biological material and the differences in bone development resulting from age, gender and ethnic origin. Content-based image retrieval (CBIR) provides a robust solution without delineating and measuring bones. In this work, epiphyseal ROIs (eROIS) of a hand radiograph are compared to previous cases with known age, mimicking a human observer. Leaving-one-out experiments are conducted on 1,102 left hand radiographs and 15,428 metacarpal and phalangeal eROIs from the publicly available USC hand atlas. The similarity of the eROIs is assessed by a combination of cross-correlation, image distortion model, and Tamura texture features, yielding a mean error rate of 0.97 years and a variance of below 0.63 years. Furthermore, we introduce a publicly available online-demonstration system, where queries on the USC dataset as well as on uploaded radiographs are performed for instant CAD. In future, we plan to evaluate physician with CBIR-CAD against physician without CBIR-CAD rather than physician vs. CBIR-CAD.

  8. Dietary Polyphenols, Berries, and Age-Related Bone Loss: A Review Based on Human, Animal, and Cell Studies

    PubMed Central

    Hubert, Patrice A.; Lee, Sang Gil; Lee, Sun-Kyeong; Chun, Ock K.

    2014-01-01

    Bone loss during aging has become an increasing public health concern as average life expectancy has increased. One of the most prevalent forms of age-related bone disease today is osteoporosis in which the body slows down bone formation and existing bone is increasingly being resorbed by the body to maintain the calcium balance. Some causes of this bone loss can be attributed to dysregulation of osteoblast and osteoclast activity mediated by increased oxidative stress through the aging process. Due to certain serious adverse effects of the currently available therapeutic agents that limit their efficacy, complementary and alternative medicine (CAM) has garnered interest as a natural means for the prevention of this debilitating disease. Natural antioxidant supplementation, a type of CAM, has been researched to aid in reducing bone loss caused by oxidative stress. Naturally occurring polyphenols, such as anthocyanins rich in berries, are known to have anti-oxidative properties. Several studies have been reviewed to determine the impact polyphenol intake—particularly that of berries—has on bone health. Studies reveal a positive association of high berry intake and higher bone mass, implicating berries as possible inexpensive alternatives in reducing the risk of age related bone loss. PMID:26784669

  9. Neuropathologic basis of white matter hyperintensity accumulation with advanced age

    PubMed Central

    Woltjer, Randall; Kaye, Jeffrey; Mattek, Nora; Dodge, Hiroko H.; Green, Sarah; Tran, Huong; Howieson, Diane B.; Wild, Katherine; Silbert, Lisa C.

    2013-01-01

    Objective: To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. Methods: Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p < 0.1. Results: Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). Conclusion: Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter. PMID:23935177

  10. Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

    NASA Technical Reports Server (NTRS)

    Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

    2016-01-01

    The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

  11. Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

    SciTech Connect

    McGlave, P.B.; Miller, W.J.; Hurd, D.D.; Arthur, D.C.; Kim, T.

    1981-11-01

    We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern or demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

  12. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    SciTech Connect

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-15

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  13. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    NASA Astrophysics Data System (ADS)

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-01

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  14. p47phox-Nox2-dependent ROS Signaling Inhibits Early Bone Development in Mice but Protects against Skeletal Aging*

    PubMed Central

    Chen, Jin-Ran; Lazarenko, Oxana P.; Blackburn, Michael L.; Mercer, Kelly E.; Badger, Thomas M.; Ronis, Martin J. J.

    2015-01-01

    Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Progressive accumulation of reactive oxygen species (ROS) has been suspected to be the leading cause of many inflammatory and degenerative diseases, as well as an important factor underlying many effects of aging. In contrast, how reduced ROS signaling regulates inflammation and remodeling in bone remains unknown. Here, we utilized a p47phox knock-out mouse model, in which an essential cytosolic co-activator of Nox2 is lost, to characterize bone metabolism at 6 weeks and 2 years of age. Compared with their age-matched wild type controls, loss of Nox2 function in p47phox−/− mice resulted in age-related switch of bone mass and strength. Differences in bone mass were associated with increased bone formation in 6-week-old p47phox−/− mice but decreased in 2-year-old p47phox−/− mice. Despite decreases in ROS generation in bone marrow cells and p47phox-Nox2 signaling in osteoblastic cells, 2-year-old p47phox−/− mice showed increased senescence-associated secretory phenotype in bone compared with their wild type controls. These in vivo findings were mechanistically recapitulated in ex vivo cell culture of primary fetal calvarial cells from p47phox−/− mice. These cells showed accelerated cell senescence pathway accompanied by increased inflammation. These data indicate that the observed age-related switch of bone mass in p47phox-deficient mice occurs through an increased inflammatory milieu in bone and that p47phox-Nox2-dependent physiological ROS signaling suppresses inflammation in aging. PMID:25922068

  15. Hemi body irradiation: An economical way of palliation of pain in bone metastasis in advanced cancer

    PubMed Central

    Pal, Santanu; Dutta, Samrat; Adhikary, Shyam Sundar; Bhattacharya, Biswamit; Ghosh, Balaram; Patra, Niladri B.

    2014-01-01

    Background: The primary aim of this prospective non-randomized study was to evaluate the effect of hemi-body irradiation (HBI) on pain and quality of life in cancer patients with extensive bone metastases. The secondary aim was to evaluate side-effects and cost-effectiveness of the treatment. Materials and Methods: Between March 2008 and December 2010, a total of 23 (male = 14, female = 9, median age = 60 years) diagnosed cases of metastatic cancer patients (prostate = 11, breast = 6, and lung = 6) received HBI, which was delivered as lower (n = 7) (dose = 8 Gy), upper (n = 8) (dose = 6 Gy), or sequential HBI (n = 8) with a Telecobalt unit (Theratron 780C). Among them, one lung cancer patient died at 2 months and one prostate cancer patient defaulted after the second follow-up. Thus, 21 patients (male = 13, female = 8, median age = 65 years) (prostatic cancer = 10, breast cancer = 6, and lung cancer = 5) were followed up for a minimum of 6 months. Evaluations were performed before and at 2, 4, 8, 16, and 24 weeks after treatment. Pain evaluation was done by Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), Percentage of Pain Relief (PRR), and Global Pain Score (GPS). Toxicity was assessed by CTC v-3 toxicity scores in the medical record. Assessment of oral morphine consumption was done before and after radiation using paired t-test, and correlation analysis was also done with decrease of morphine consumption and reduction of pain score using statistical analysis. Results: Response (control of pain) was partial (PR) in 67% and complete (CR) in 22% of patients. For most patients, the pain control lasted throughout the follow-up period (6 months). From 66.66% patients requiring 13 or more Morphine (10 mg) tablets per day prior to HBI, none of the patients required to consume 13 or more Morphine (10 mg) tablets per day following HBI, which was correlated with significant reduction in various pain scores (P < 0.05). One way ANOVA with Dunnett's Multiple Comparison

  16. The applicability of the Greulich & Pyle Atlas for bone age assessment in primary school-going children of Karachi, Pakistan

    PubMed Central

    Manzoor Mughal, Arsalan; Hassan, Nuzhat; Ahmed, Anwar

    2014-01-01

    Objective: To assess the degree of applicability of bone age calculated by Greulich & Pyle Atlas in estimation of chronological age for therapeutic and medico legal purposes. Methods: Two Hundred and Twenty children (139 males, 81 females) between ages of 56 and 113 months (4.5 to 9.5 years) were randomly selected from 4 primary schools of Shireen Jinnah & Clifton, Karachi. Digital images of hand and wrist radiographs were obtained by a computed radiography at Ziauddin Hospital Clifton. Bone ages were computed using Greulich & Pyle Atlas by radiologists at Ziauddin Hospital, North Nazimabad, Karachi. Results: On average, the Greulich & Pyle Atlas underestimates chronological age by 6.65 ± 13.47 months in females and 15.78 ± 12.83 months in males (p-values < 0.001). High correlation was found between chronological age and bone age in both genders (Females r=0.778; p-value< 0.001, Males r=0.816; p-value < 0.001). Conclusion: Bone age calculated by Greulich & Pyle Atlas should not be used for estimating chronological age in children of ages 56-113 months in situations where high accuracy is required (e.g. medicolegal cases). However, serial measurements of bone age by this atlas can be used in management of growth related endocrine disorders in these children. PMID:24772153

  17. Changes in bone tissue under conditions of hypokinesia and in connection with age

    NASA Technical Reports Server (NTRS)

    Podrushnyak, E. P.; Suslov, E. I.

    1980-01-01

    X-ray micrography was used to study the optical density of the blackening of X-ray photographs made of five bones in 9 young people (ages 24 to 29) before and after strict bed rest for 16 to 37 days. Photometric studies of the X-ray film determined the relative concentration of bone structure before and after hypokinesia. In addition, the bone tissues of 25 cadavers of practically healthy individuals (aged 18 to 70) who died from injuries were investigated using X-ray structural analysis. Results show that the reaction to the state of hypokinesia is not uniform in different individuals and is quite often directly reversed. It was established that pronounced osteoporosis can be found in a relatively short time after conditions of hypokinesia in healthy young individuals. Results show that the stabilization of the crystalline structure of hydroxyapatite, especially its crystal formation, is finished by the age of 20 to 25. From 25 to 60, the crystal lattice remains in stable condition but X-ray analysis shows a reduction in the hydroxyapatite density.

  18. Advanced maternal age and risk perception: A qualitative study

    PubMed Central

    2012-01-01

    Background Advanced maternal age (AMA) is associated with several adverse pregnancy outcomes, hence these pregnancies are considered to be “high risk.” A review of the empirical literature suggests that it is not clear how women of AMA evaluate their pregnancy risk. This study aimed to address this gap by exploring the risk perception of pregnant women of AMA. Methods A qualitative descriptive study was undertaken to obtain a rich and detailed source of explanatory data regarding perceived pregnancy risk of 15 women of AMA. The sample was recruited from a variety of settings in Winnipeg, Canada. In-depth interviews were conducted with nulliparous women aged 35 years or older, in their third trimester, and with singleton pregnancies. Interviews were recorded and transcribed verbatim, and content analysis was used to identify themes and categories. Results Four main themes emerged: definition of pregnancy risk, factors influencing risk perception, risk alleviation strategies, and risk communication with health professionals. Conclusions Several factors may influence women's perception of pregnancy risk including medical risk, psychological elements, characteristics of the risk, stage of pregnancy, and health care provider’s opinion. Understanding these influential factors may help health professionals who care for pregnant women of AMA to gain insight into their perspectives on pregnancy risk and improve the effectiveness of risk communication strategies with this group. PMID:22988825

  19. AGE-RELATED FACTORS AFFECTING THE POST-YIELD ENERGY DISSIPATION OF HUMAN CORTICAL BONE

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Tyler, Jerrod H.; Acuna, Rae L.; Gayle, Heather J.; Wang, Xiaodu

    2007-01-01

    The risk of bone fracture depends in part on the quality of the tissue, not just the size and mass. This study assessed the post-yield energy dissipation of cortical bone in tension as a function of age and composition. Tensile specimens were prepared from tibiae of human cadavers in which male and female donors were divided into two age groups: middle aged (51 to 56 years old, n = 9) and elderly (72 to 90 years old, n = 8). By loading, unloading, and reloading a specimen with rest period inserted in between, tensile properties at incremental strain levels were assessed. In addition, the post-yield toughness was estimated and partitioned as follows: plastic strain energy related to permanent deformation, released elastic strain energy related to stiffness loss, and hysteresis energy related to viscous behavior. Porosity, mineral and collagen content, and collagen crosslinks of each specimen were also measured to determine the micro and ultrastructural properties of the tissue. It was found that age affected all the energy terms plus strength but not elastic stiffness. The post-yield energy terms were correlated with porosity, pentosidine (a marker of non-enzymatic crosslinks), and collagen content, all of which significantly varied with age. General linear models with the highest possible R2 value suggested that the pentosidine concentration and collagen content provided the best explanation of the age-related decrease in the post-yield energy dissipation of bone. Among them, pentosidine concentration had the greatest contribution to plastic strain energy and was the best explanatory variable of damage accumulation. PMID:17266142

  20. Multipurpose contrast enhancement on epiphyseal plates and ossification centers for bone age assessment

    PubMed Central

    2013-01-01

    Background The high variations of background luminance, low contrast and excessively enhanced contrast of hand bone radiograph often impede the bone age assessment rating system in evaluating the degree of epiphyseal plates and ossification centers development. The Global Histogram equalization (GHE) has been the most frequently adopted image contrast enhancement technique but the performance is not satisfying. A brightness and detail preserving histogram equalization method with good contrast enhancement effect has been a goal of much recent research in histogram equalization. Nevertheless, producing a well-balanced histogram equalized radiograph in terms of its brightness preservation, detail preservation and contrast enhancement is deemed to be a daunting task. Method In this paper, we propose a novel framework of histogram equalization with the aim of taking several desirable properties into account, namely the Multipurpose Beta Optimized Bi-Histogram Equalization (MBOBHE). This method performs the histogram optimization separately in both sub-histograms after the segmentation of histogram using an optimized separating point determined based on the regularization function constituted by three components. The result is then assessed by the qualitative and quantitative analysis to evaluate the essential aspects of histogram equalized image using a total of 160 hand radiographs that are implemented in testing and analyses which are acquired from hand bone online database. Result From the qualitative analysis, we found that basic bi-histogram equalizations are not capable of displaying the small features in image due to incorrect selection of separating point by focusing on only certain metric without considering the contrast enhancement and detail preservation. From the quantitative analysis, we found that MBOBHE correlates well with human visual perception, and this improvement shortens the evaluation time taken by inspector in assessing the bone age. Conclusions

  1. Advances in the surface modification techniques of bone-related implants for last 10 years

    PubMed Central

    Qiu, Zhi-Ye; Chen, Cen; Wang, Xiu-Mei; Lee, In-Seop

    2014-01-01

    At the time of implanting bone-related implants into human body, a variety of biological responses to the material surface occur with respect to surface chemistry and physical state. The commonly used biomaterials (e.g. titanium and its alloy, Co–Cr alloy, stainless steel, polyetheretherketone, ultra-high molecular weight polyethylene and various calcium phosphates) have many drawbacks such as lack of biocompatibility and improper mechanical properties. As surface modification is very promising technology to overcome such problems, a variety of surface modification techniques have been being investigated. This review paper covers recent advances in surface modification techniques of bone-related materials including physicochemical coating, radiation grafting, plasma surface engineering, ion beam processing and surface patterning techniques. The contents are organized with different types of techniques to applicable materials, and typical examples are also described. PMID:26816626

  2. Correlating chemical changes in subchondral bone mineral due to aging or defective type II collagen by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Dehring, Karen A.; Roessler, Blake J.; Morris, Michael D.

    2007-02-01

    We show that early indicators of osteoarthritis are observed in Raman spectroscopy by probing femur surfaces excised from mouse models of early-onset osteoarthritis. Current clinical methods to examine arthritic joints include radiological examination of the joint, but may not be capable of detecting subtle chemical changes in the bone tissue, which may provide the earliest indications of osteoarthritis. Recent research has indicated that the subchondral bone may have a more significant role in the onset of osteoarthritis than previously realized. We will report the effect of age and defective type II collagen on Raman band area ratios used to describe bone structure and function. The carbonate-to-phosphate ratio is used to assess carbonate substitution into the bone mineral and the mineral-to-matrix ratio is used to measure bone mineralization. Mineral-to-matrix ratios indicate that subchondral bone becomes less mineralized as both the wild-type and Del1 (+/-) transgenic mice age. Moreover, the mineral-to-matrix ratios show that the subchondral bone of Del1 (+/-) transgenic mice is less mineralized than that of the wild-type mice. Carbonate-to-phosphate ratios from Del1 (+/-) transgenic mice follow the same longitudinal trend as wild-type mice. The ratio is slightly higher in the transgenic mice, indicating more carbonate content in the bone mineral. Raman characterization of bone mineralization provides an invaluable insight into the process of cartilage degeneration and the relationship with subchondral bone at the ultrastructural level.

  3. Bone-targeting endogenous secretory receptor for advanced glycation end products rescues rheumatoid arthritis.

    PubMed

    Takahashi, Tatsuo; Katsuta, Sayaka; Tamura, Yusuke; Nagase, Nozomi; Suzuki, Keita; Nomura, Masaaki; Tomatsu, Shunji; Miyamoto, Ken-Ichi; Kobayashi, Shinjiro

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory synovitis that leads to the destruction of bone and cartilage. The receptor for advanced glycation end products (RAGE) is a multiligand membrane-bound receptor for high-mobility group box-1 (HMGB1) associated with development of RA by inducing production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6. We developed a bone-targeting therapeutic agent by tagging acidic oligopeptide to a nonmembrane-bound form of RAGE (endogenous secretory RAGE [esRAGE]) functioning as a decoy receptor. We assessed its tissue distribution and therapeutic effectiveness in a murine model of collagen-induced arthritis (CIA). Acidic oligopeptide-tagged esRAGE (D6-esRAGE) was localized to mineralized region in bone, resulting in the prolonged retention of more than 1 wk. Weekly administration of D6-esRAGE with a dose of 1 mg/kg to RA model mice significantly ameliorated inflammatory arthritis, synovial hyperplasia, cartilage destruction and bone destruction, while untagged esRAGE showed little effectiveness. Moreover, D6-esRAGE reduced plasma levels of proinflammatory cytokines including TNF-α, IL-1 and IL-6, while esRAGE reduced the levels of IL-1 and IL-6 to a lesser extent, suggesting that production of IL-1 and IL-6 reduced along the blockade of HMGB1 receptor downstream signals by D6-esRAGE could be attributed to remission of CIA. These findings indicate that D6-esRAGE enhances drug delivery to bone, leading to rescue of clinical and pathological lesions in murine CIA. PMID:23821362

  4. Reference data for ultrasonic bone measurement: variation with age in 2087 Caucasian women aged 16-93 years.

    PubMed

    Truscott, J G

    1997-10-01

    Data from the measurement of broadband ultrasonic attenuation (BUA) and speed of sound (SOS), using the Lunar Achilles ultrasonic densitometer, were collected for Caucasian women from five centres in the United Kingdom (Leeds, London, Nottingham, Lincoln and Sheffield). After correcting for machine variability at each site, the data were combined into a central reference database comprising 2087 women aged 16-93 years. The data are presented in 5-year bands and show a mean fall of 0.36% per year for BUA and 0.08% per year for SOS in the 60 years following the attainment of peak bone mass. This fall in BUA compares with that observed using dual energy X-ray absorptiometry studies of the lumbar spine and femoral neck of 0.32% per year and 0.44% per year, respectively, for the age range 25-65 years. PMID:9404204

  5. Cortical Bone Water Concentration: Dependence of MR Imaging Measures on Age and Pore Volume Fraction

    PubMed Central

    Li, Cheng; Seifert, Alan C.; Rad, Hamidreza Saligheh; Bhagat, Yusuf A.; Rajapakse, Chamith S.; Sun, Wenli; Lam, Shing Chun Benny

    2014-01-01

    Purpose To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. Materials and Methods Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20–80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against micro-CT–derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. Results BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = −0.57; 95% CI: −0.76, −0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = −0.67, 95% CI: −0.82, −0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). Conclusion The MR imaging–derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated. © RSNA, 2014 PMID

  6. Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly men.

    PubMed

    Kahn, Arnold J; Halloran, Bernard; Wolkowitz, Owen; Brizendine, Louann

    2002-04-01

    In the present placebo-controlled, double-blind study, we assessed the effect of dehydroepiandrosterone (DHEA) supplementation (90 mg orally/d) on bone turnover in 43 healthy men, 56-80 yr old. Placebo or steroid was given for 6 months, followed by a 1-month washout period and then a further 6 months of the opposite agent. Serum samples were collected at baseline 3, 6, 7, and 13 months and assayed for procollagen peptide, bone-specific alkaline phosphatase, and osteocalcin, all markers of bone formation. Measurements were also made of serum cortisol, DHEA/DHEA-S, E2 and free and total T. First void, fasting urine was collected at baseline, 6, 7, and 13 months and assessed for deoxypyridinoline, a marker of bone resorption. Mean serum DHEA and DHEA-S levels in treated men were increased approximately 3-fold ( approximately 2.2 ng/ml to approximately 6 ng/ml) and 4.5-fold ( approximately 1000 ng/ml to approximately 4500 ng/ml), respectively, after 6 months and returned to baseline after washout. Similarly, circulating E2 concentrations were also increased 1.4-fold (from approximately 16-23 pg/ml; P < 0.001), a finding not observed with any other measured hormone. Bone marker levels remained remarkably constant at each sampling interval; procollagen peptide at approximately 8.0 ng/ml; bone-specific alkaline phosphatase at approximately 21.0 U/liter; deoxypyridinoline at approximately 4.5 nmol/mmol Cr. Osteocalcin showed a transient reduction from approximately 10.2- 6.2 ng/ml, P < 0.005 to P < 0.001, at 3 months, but this decline was observed in both treated and controls. Stratifying the marker levels by age or baseline DHEA/DHEA-S levels did not affect the findings. We conclude that oral DHEA does not affect bone turnover in middle-aged to elderly men when used for a 6-month period at doses targeted to restore circulating levels of the steroid to that seen in young adults. PMID:11932279

  7. Monitoring Bone Health after Spaceflight: Data Mining to Support an Epidemiological Analysis of Age-related Bone Loss in Astronauts

    NASA Technical Reports Server (NTRS)

    Baker, K. S,; Amin, S.; Sibonga, Jean D.

    2009-01-01

    Through the epidemiological analysis of bone data, HRP is seeking evidence as to whether the prolonged exposure to microgravity of low earth orbit predisposes crewmembers to an earlier onset of osteoporosis. While this collaborative Epidemiological Project may be currently limited by the number of ISS persons providing relevant spaceflight medical data, a positive note is that it compares medical data of astronauts to data of an age-matched (not elderly) population that is followed longitudinally with similar technologies. The inclusion of data from non-ISS and non-NASA crewmembers is also being pursued. The ultimate goal of this study is to provide critical information for NASA to understand the impact of low physical or minimal weight-bearing activity on the aging process as well as to direct its development of countermeasures and rehabilitation programs to influence skeletal recovery. However, in order to optimize these results NASA needs to better define the requirements for long term monitoring and encourage both active and retired astronauts to contribute to a legacy of data that will define human health risks in space.

  8. Contribution of dietary advanced glycation end products (AGE) to circulating AGE: role of dietary fat.

    PubMed

    Davis, Kathleen E; Prasad, Chandan; Vijayagopal, Parakat; Juma, Shanil; Adams-Huet, Beverley; Imrhan, Victorine

    2015-12-14

    The purpose of this pilot study was to determine whether macronutrient content (low-fat v. high-fat diet) influences an indicator of advanced glycation end products (AGE), N(ε) carboxymethyl-lysine (CML), in the context of a 1-d, high-AGE diet. The effect of the diets on inflammatory markers was also assessed. A total of nineteen overweight and obese adults (nine men and ten women) without known disease were recruited to participate in a crossover challenge of a high-fat, high-AGE (HFHA) and low-fat, high-AGE (LFHA) diet. In each phase patients had fasting blood drawn, followed by consumption of a high-fat or low-fat breakfast test meal, then three postprandial blood draws at 1, 2 and 3 h after consuming the test meal. After consuming high-AGE meals for the remainder of the day, participants returned the next day for a follow-up analysis. A different pattern in the 3-h post-meal CML and soluble receptor for AGE response to the two diets was observed (P=0·01 and 0·05, respectively). No change in serum CML was observed following consumption of a LFHA breakfast (535 (25th-75th percentile 451-790) to 495 (25th-75th percentile 391-682) ng/ml; P=0·36), whereas a rise in CML occurred after the HFHA breakfast (463 (25th-75th percentile 428-664) to 578 (25th-75th percentile 474-865) ng/ml; P=0·05). High sensitivity C-reactive protein and high molecular weight adiponectin were not affected by either diet. These findings suggest that dietary CML may not be as important in influencing serum CML as other dietary factors. In addition, acute exposure to dietary CML may not influence inflammation in adults without diabetes or kidney disease. This is contrary to previous findings. PMID:26392152

  9. Bone density of the arm and forearm as an age indicator in specimens of stranded striped dolphins (Stenella coeruleoalba).

    PubMed

    Guglielmini, Carlo; Zotti, Alessandro; Bernardini, Daniele; Pietra, Marco; Podestá, Michela; Cozzi, Bruno

    2002-07-01

    The age of odontocetes living in the wild is determined mainly by analysis of dentine layers in sections of the teeth. We examined a series of specimens from striped dolphins (Stenella coeruleoalba, Meyen, 1833) that had stranded along the Italian coast of the Mediterranean sea. The present study analyzes and describes bone density in the arm and forearm of the stranded specimens, and correlates the data with total body length of the animal and age as determined by the number of dentine layers in sections of the teeth. According to our model, age can be predicted on the basis of bone density and total body length of the stranded animal. This is the first study to use bone density as a biological parameter to understand the wear and tear of life in the sea. The results suggest that bone density is a new tool for recording age in wild odontocetes. PMID:12115272

  10. Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice.

    PubMed

    Alund, Alexander W; Mercer, Kelly E; Suva, Larry J; Pulliam, Casey F; Chen, Jin-Ran; Badger, Thomas M; Van Remmen, Holly; Ronis, Martin J J

    2016-07-01

    Chronic ethyl alcohol (EtOH) consumption results in reactive oxygen species (ROS) generation in bone and osteopenia due to increased bone resorption and reduced bone formation. In this study, transgenic C57Bl/6J mice overexpressing human catalase (TgCAT) were used to test whether limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. Micro-computed tomography analysis of the skeletons of 6-week-old female chow-fed TgCAT mice revealed a high bone mass phenotype with increased cortical bone area and thickness as well as significantly increased trabecular bone volume (P < 0.05). Six-week-old wild-type (WT) and TgCAT female mice were chow fed or pair fed (PF) liquid diets with or without EtOH, approximately 30% of calories, for 8 weeks. Pair feeding of WT had no demonstrable effect on the skeleton; however, EtOH feeding of WT mice significantly reduced cortical and trabecular bone parameters along with bone strength compared with PF controls (P < 0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared with PF controls. At 14 weeks of age, there was significantly less trabecular bone and cortical cross-sectional area in TgCAT mice than WT mice (P < 0.05), suggesting impaired normal bone accrual with age. TgCAT mice expressed less collagen1α and higher sclerostin mRNA (P < 0.05), suggesting decreased bone formation in TgCAT mice. In conclusion, catalase overexpression resulted in greater bone mass than in WT mice at 6 weeks and lower bone mass at 14 weeks. EtOH feeding induced significant reductions in bone architecture and strength in WT mice, but TgCAT mice were partially protected. These data implicate ROS signaling in the regulation of bone turnover in an age-dependent manner, and indicate that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia. PMID:27189961

  11. Sclerostin Immunoreactivity Increases in Cortical Bone Osteocytes and Decreases in Articular Cartilage Chondrocytes in Aging Mice.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W

    2016-03-01

    Sclerostin is a 24-kDa secreted glycoprotein that has been identified as a negative modulator of new bone formation and may play a major role in age-related decline in skeletal function. Although serum levels of sclerostin markedly increase with age, relatively little is known about whether cells in the skeleton change their expression of sclerostin with aging. Using immunohistochemistry and confocal microscopy, we explored sclerostin immunoreactivity (sclerostin-IR) in the femurs of 4-, 9-, and 24-month-old adult C3H/HeJ male mice. In the femur, the only two cell types that expressed detectable levels of sclerostin-IR were bone osteocytes and articular cartilage chondrocytes. At three different sites along the diaphysis of the femur, only a subset of osteocytes expressed sclerostin-IR and the percentage of osteocytes that expressed sclerostin-IR increased from approximately 36% to 48% in 4- vs. 24-month-old mice. In marked contrast, in the same femurs, there were ~40% fewer hypertrophic chondrocytes of articular cartilage that expressed sclerostin-IR when comparing 24- vs. 4-month-old mice. Understanding the mechanism(s) that drive these divergent changes in sclerostin-IR may provide insight into understanding and treating the age-related decline of the skeleton. PMID:26701970

  12. A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength.

    PubMed

    Arounleut, Phonepasong; Bialek, Peter; Liang, Li-Fang; Upadhyay, Sunil; Fulzele, Sadanand; Johnson, Maribeth; Elsalanty, Mohammed; Isales, Carlos M; Hamrick, Mark W

    2013-09-01

    Loss of muscle and bone mass with age are significant contributors to falls and fractures among the elderly. Myostatin deficiency is associated with increased muscle mass in mice, dogs, cows, sheep and humans, and mice lacking myostatin have been observed to show increased bone density in the limb, spine, and jaw. Transgenic overexpression of myostatin propeptide, which binds to and inhibits the active myostatin ligand, also increases muscle mass and bone density in mice. We therefore sought to test the hypothesis that in vivo inhibition of myostatin using an injectable myostatin propeptide (GDF8 propeptide-Fc) would increase both muscle mass and bone density in aged (24 mo) mice. Male mice were injected weekly (20 mg/kg body weight) with recombinant myostatin propeptide-Fc (PRO) or vehicle (VEH; saline) for four weeks. There was no difference in body weight between the two groups at the end of the treatment period, but PRO treatment significantly increased mass of the tibialis anterior muscle (+ 7%) and increased muscle fiber diameter of the extensor digitorum longus (+ 16%) and soleus (+ 6%) muscles compared to VEH treatment. Bone volume relative to total volume (BV/TV) of the femur calculated by microCT did not differ significantly between PRO- and VEH-treated mice, and ultimate force (Fu), stiffness (S), toughness (U) measured from three-point bending tests also did not differ significantly between groups. Histomorphometric assays also revealed no differences in bone formation or resorption in response to PRO treatment. These data suggest that while developmental perturbation of myostatin signaling through either gene knockout or transgenic inhibition may alter both muscle and bone mass in mice, pharmacological inhibition of myostatin in aged mice has a more pronounced effect on skeletal muscle than on bone. PMID:23832079

  13. Primary bone osteosarcoma in the pediatric age: state of the art.

    PubMed

    Longhi, Alessandra; Errani, Costantino; De Paolis, Massimiliano; Mercuri, Mario; Bacci, Gaetano

    2006-10-01

    The current combination treatment, chemotherapy and surgery, has significantly improved the cure rate and the survival rate of primary bone osteosarcoma. The 5-year survival rate has increased in the last 30 years from 10% to 70%. Even in patients with poor prognosis, such as those with metastases at diagnosis, the 5-year survival rate has reached 20-30% due to chemotherapy and the surgical removal of metastases and primary tumor. However, the most effective drugs are still the same as those employed over the last 20 years as front line neoadjuvant or adjuvant chemotherapy: Doxorubicin, Cisplatin, Methotrexate, Ifosfamide. No standard, second line therapy exists for those who relapse. At relapse, due to the lack of new non-cross-resistant drugs, surgery is still the main option when feasible. Other drugs have been employed in relapsed patients with poor results. This article reviews the state of the art of treatment for bone osteosarcoma in the pediatric age. PMID:16860938

  14. Premature aging in bone of fish from a highly polluted marine area.

    PubMed

    Scopelliti, Giovanna; Di Leonardo, Rossella; Tramati, Cecilia D; Mazzola, Antonio; Vizzini, Salvatrice

    2015-08-15

    Fish species have attracted considerable interest in studies assessing biological responses to environmental contaminants. In this study, the attention has been focussed on fishbone of selected fish species from a highly polluted marine area, Augusta Bay (Italy, Central Mediterranean) to evaluate if toxicant elements had an effect on the mineralogical structure of bones, although macroscopic deformations were not evident. In particular, an attempt was made to evaluate if bone mineral features, such as crystallinity, mineral maturity and carbonate/phosphate mineral content, determined by XR-Diffraction and FT-IR Spectroscopy, suffered negative effects due to trace element levels in fishbone, detected by ICP-OES. Results confirmed the reliability of the use of diffractometric and spectroscopic techniques to assess the degree of crystallinity and the mineral maturity in fishbone. In addition, in highly polluted areas, Hg and Cr contamination induced a process of premature aging of fishbone, altering its biochemical and mineral contents. PMID:26073800

  15. Occupational Determinants of Cumulative Lead Exposure: Analysis of Bone Lead Among Men in the VA Normative Aging Study

    PubMed Central

    Ji, John S.; Schwartz, Joel; Sparrow, David; Hu, Howard; Weisskopf, Marc G.

    2014-01-01

    Objectives To examine the relation between occupation and cumulative lead exposure—assessed by measuring bone lead—in a community-dwelling population Method We measured bone lead concentration with K-shell X-Ray Fluorescence in 1,320 men in the Normative Aging Study. We categorized job titles into 14 broad US Census Bureau categories. We used ordinary least squares regression to estimate bone lead by job categories adjusted for other predictors. Results Service Workers, Construction and Extractive Craft Workers, and Installation, Maintenance and Repair Craft Workers had the highest bone lead concentrations. Including occupations significantly improved the overall model (p<0.001) and reduced by −15% to −81% the association between bone lead and education categories. Conclusion Occupation significantly predicts cumulative lead exposure in a community-dwelling population, and accounts for a large proportion of the association between education and bone lead. PMID:24709766

  16. Effect of age on bone mineral density and micro architecture in the radius and tibia of horses: An Xtreme computed tomographic study

    PubMed Central

    Fürst, A; Meier, D; Michel, S; Schmidlin, A; Held, L; Laib, A

    2008-01-01

    Background The effect of age on the bone mineral density and microarchitecture of the equine radius and tibia was investigated. Fifty-six bones from 15 horses aged four to 21 years were used. There were nine geldings and six mares, and none of the horses had any disease influencing bone properties. Xtreme computed tomography was used to evaluate a 9-mm segment of the diaphysis and metaphysis of each bone. The following variables were determined: length of the bone, circumference and diameter in the frontal and sagittal planes in the middle of the bone. Diaphysis: total volume, bone volume, bone volume ratio, slice area, bone area, marrow area, cortical and marrow thickness, bone mineral density, polar moment of inertia of the cortex. Metaphysis: total area, bone area, cortical bone area, cortical thickness, bone mineral density, bone mineral density in the cortex, bone mineral density in the trabecular region, trabecular number, trabecular thickness, trabecular separation, polar moment of inertia of the metaphysis, polar moment of inertia of the cortex of the metaphysis. Results Bone density and microarchitecture were not affected by breed or gender. However, the microarchitecture varied with the age of the horse; the number of trabeculae decreased significantly and the distance between trabeculae increased significantly with increasing age. There were no significant differences between bones of the left and right limbs or between the radius and tibia. Conclusion The variables investigated did not differ between geldings and mares. However, there were age-related changes in the microstructure of the bones. Further experimental studies are necessary to determine whether these changes reduce bone strength. Age-related changes in the bones were seen and may explain the higher incidence of fractures and fissures in older horses. PMID:18221526

  17. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  18. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  19. EFFECT OF AGE ON MECHANICAL PROPERTIES OF THE COLLAGEN PHASE IN DIFFERENT ORIENTATIONS OF HUMAN CORTICAL BONE

    PubMed Central

    Leng, Huijie; Reyes, Michael J; Dong, Neil X; Wang, Xiaodu

    2013-01-01

    The collagen phase plays an important role in mechanical behaviors of cortical bone. However, aging effects on the mechanical behavior of the collagen phase is still poorly understood. In this study, micro-tensile tests were performed on demineralized human cortical bone samples from young, middle-aged, and elderly donors and aging effects on the mechanical properties of the collagen phase in different orientations (i.e. longitudinal and transverse directions of bone) were examined. The results of this study indicated that the elastic modulus and ultimate strength of the demineralized bone specimens decreased with aging in both the longitudinal and transverse orientations. However, the failure strain exhibited no significant changes in both orientations regardless of aging. These results suggest that the stiffness and strength of the collagen phase in bone are deteriorated with aging in both longitudinal and transverse directions. However, the aging effect is not reflected in the failure strain of the collagen phase in both longitudinal and transverse orientations, implying that the maximum sustainable deformation of the collagen phase is independent of aging and orientation. PMID:23598045

  20. Effects of age, sex, and ethnicity on bone health status of the elderly in Kuala Lumpur, Malaysia

    PubMed Central

    Chin, Kok-Yong; Kamaruddin, Alia Annessa Ain; Low, Nie Yen; Ima-Nirwana, Soelaiman

    2016-01-01

    Background Osteoporosis is a significant health problem in the developing countries and its prevalence data are important for the estimation of health care burden and policy making. This study aimed to determine the age-related changes in bone health and the prevalence of osteoporosis in males and females aged 50 years or above living in Kuala Lumpur, Malaysia. Methods A cross-sectional study was conducted between December 2014 and December 2015. Subjects answered a demographic questionnaire and underwent body anthropometric and bone health measurement. Assessment of bone health was performed using a quantitative ultrasound device that generated speed of sound, broadband ultrasound attenuation, stiffness index, and T-score based on stiffness index value as bone health indices. Results The prevalence of osteoporosis was 10.6% in males and 8.0% in females. Significant age-related decline of bone health indices (speed of sound, broadband ultrasound attenuation, stiffness index, and T-score) and a concurrent increase in the prevalence of osteoporosis and osteopenia were observed in females (P<0.05) but not in males (P>0.05). Ethnic differences in bone health indices and prevalence of osteoporosis/osteopenia were not observed (P>0.05). Conclusion A significant proportion of males and females age 50 years or above have suboptimal bone health. Preventive measures such as early screening should be implemented to retard the progression of osteoporosis. PMID:27358558

  1. Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism.

    PubMed

    Friedl, Gerald; Turner, Russell T; Evans, Glenda L; Dobnig, Harald

    2007-11-01

    In recent years, intermittent PTH treatment has been investigated extensively for its efficacy in preventing osteoporotic fractures and to improve fracture healing and implant fixation. Although these tasks concern patients of all ages, very little is known about whether aging impacts the bone anabolic response to PTH. Female Sprague-Dawley rats of 1, 3, and 13 months of age were either treated by hPTH-(1-34) or by vehicle solution (CTR) for 1 week. As main outcome measures, we determined the effects on static and dynamic histomorphometry of cancellous bone. In addition, we measured gene expression in femur and serum parameters reflecting bone turnover and mineral metabolism. There was a profound decrease in bone formation rate (BFR) with aging in CTR rats, whereas PTH treatment resulted in a significant relative 1.5-, 3-, and 4.7-fold increase in BFR, without altering indices of bone resorption. Aging decreased and PTH increased mRNA levels for bone matrix proteins and growth factors in a gene-specific manner. In younger animals, PTH-induced a marked stimulation in the mineral apposition rate with no effect on osteoblast number, whereas the latter was increased in older animals (1.0-, 1.7-, and 3.1-fold). Treatment with PTH in young rats led to a significant increase in trabecular number (1.6-2.6/mm, p < 0.05), whereas older rats demonstrated increases in trabecular thickness only (52.8-77.8 microm, p < 0.001). Although PTH increased bone formation at all ages, we found significant age-related differences in the cellular and molecular mechanisms involved in the bone anabolic response to the hormone. PMID:17557320

  2. Age-Related Modulation of the Effects of Obesity on Gene Expression Profiles of Mouse Bone Marrow and Epididymal Adipocytes

    PubMed Central

    Liu, Li-Fen; Shen, Wen-Jun; Ueno, Masami; Patel, Shailja; Azhar, Salman; Kraemer, Fredric B.

    2013-01-01

    This study aimed to characterize and compare the effects of obesity on gene expression profiles in two distinct adipose depots, epididymal and bone marrow, at two different ages in mice. Alterations in gene expression were analyzed in adipocytes isolated from diet-induced obese (DIO) C57BL/6J male mice at 6 and 14 months of age and from leptin deficient mice (ob/ob) at 6 months of age using microarrays. DIO affected gene expression in both depots at 6 and 14 months, but more genes were altered in epididymal than bone marrow adipocytes at each age and younger mice displayed more changes than older animals. In epididymal adipocytes a total of 2789 (9.6%) genes were differentially expressed at 6-months with DIO, whereas 952 (3.3%) were affected at 14-months. In bone marrow adipocytes, 347 (1.2%) genes were differentially expressed at 6-months with DIO, whereas only 189 (0.66%) were changed at 14-months. 133 genes were altered by DIO in both fat depots at 6-months, and 37 genes at 14-months. Only four genes were altered in both depots at both ages with DIO. Bone marrow adipocytes are less responsive to DIO than epididymal adipocytes and the response of both depots to DIO declines with age. This loss of responsiveness with age is likely due to age-associated changes in expression of genes related to adipogenesis, inflammation and mitochondrial function that are similar to and obscure the changes commonly associated with DIO. Patterns of gene expression were generally similar in epididymal adipocytes from ob/ob and DIO mice; however, several genes were differentially expressed in bone marrow adipocytes from ob/ob and DIO mice, perhaps reflecting the importance of leptin signaling for bone metabolism. In conclusion, obesity affects age-associated alterations in gene expression in both epididymal and bone marrow adipocytes regardless of diet or genetic background. PMID:23967297

  3. Age-related modulation of the effects of obesity on gene expression profiles of mouse bone marrow and epididymal adipocytes.

    PubMed

    Liu, Li-Fen; Shen, Wen-Jun; Ueno, Masami; Patel, Shailja; Azhar, Salman; Kraemer, Fredric B

    2013-01-01

    This study aimed to characterize and compare the effects of obesity on gene expression profiles in two distinct adipose depots, epididymal and bone marrow, at two different ages in mice. Alterations in gene expression were analyzed in adipocytes isolated from diet-induced obese (DIO) C57BL/6J male mice at 6 and 14 months of age and from leptin deficient mice (ob/ob) at 6 months of age using microarrays. DIO affected gene expression in both depots at 6 and 14 months, but more genes were altered in epididymal than bone marrow adipocytes at each age and younger mice displayed more changes than older animals. In epididymal adipocytes a total of 2789 (9.6%) genes were differentially expressed at 6-months with DIO, whereas 952 (3.3%) were affected at 14-months. In bone marrow adipocytes, 347 (1.2%) genes were differentially expressed at 6-months with DIO, whereas only 189 (0.66%) were changed at 14-months. 133 genes were altered by DIO in both fat depots at 6-months, and 37 genes at 14-months. Only four genes were altered in both depots at both ages with DIO. Bone marrow adipocytes are less responsive to DIO than epididymal adipocytes and the response of both depots to DIO declines with age. This loss of responsiveness with age is likely due to age-associated changes in expression of genes related to adipogenesis, inflammation and mitochondrial function that are similar to and obscure the changes commonly associated with DIO. Patterns of gene expression were generally similar in epididymal adipocytes from ob/ob and DIO mice; however, several genes were differentially expressed in bone marrow adipocytes from ob/ob and DIO mice, perhaps reflecting the importance of leptin signaling for bone metabolism. In conclusion, obesity affects age-associated alterations in gene expression in both epididymal and bone marrow adipocytes regardless of diet or genetic background. PMID:23967297

  4. High-resolution 3D imaging of osteocytes and computational modelling in mechanobiology: insights on bone development, ageing, health and disease.

    PubMed

    Goggin, P M; Zygalakis, K C; Oreffo, R O; Schneider, P

    2016-01-01

    Osteocytes are involved in mechanosensation and mechanotransduction in bone and hence, are key to bone adaptation in response to development, ageing and disease. Thus, detailed knowledge of the three-dimensional (3D) structure of the osteocyte network (ON) and the surrounding lacuno-canalicular network (LCN) is essential. Enhanced understanding of the ON&LCN will contribute to a better understanding of bone mechanics on cellular and sub-cellular scales, for instance through improved computational models of bone mechanotransduction. Until now, the location of the ON within the hard bone matrix and the sub-µm dimensions of the ON&LCN have posed significant challenges for 3D imaging. This review identifies relevant microstructural phenotypes of the ON&LCN in health and disease and summarises how light microscopy, electron microscopy and X-ray imaging techniques have been used in studies of osteocyte anatomy, pathology and mechanobiology to date. In this review, we assess the requirements for ON&LCN imaging and examine the state of the art in the fields of imaging and computational modelling as well as recent advances in high-resolution 3D imaging. Suggestions for future investigations using volume electron microscopy are indicated and we present new data on the ON&LCN using serial block-face scanning electron microscopy. A correlative approach using these high-resolution 3D imaging techniques in conjunction with in silico modelling in bone mechanobiology will increase understanding of osteocyte function and, ultimately, lead to improved pathways for diagnosis and treatment of bone diseases such as osteoporosis. PMID:27209400

  5. Peripharyngeal tissue deformation, stress distributions, and hyoid bone movement in response to mandibular advancement.

    PubMed

    Amatoury, Jason; Kairaitis, Kristina; Wheatley, John R; Bilston, Lynne E; Amis, Terence C

    2015-02-01

    Mandibular advancement (MA) increases upper airway (UA) patency and decreases collapsibility. Furthermore, MA displaces the hyoid bone in a cranial-anterior direction, which may contribute to MA-associated UA improvements via redistribution of peripharyngeal tissue stresses (extraluminal tissue pressure, ETP). In the present study, we examined effects of MA on ETP distributions, deformation of the peripharyngeal tissue surface (UA geometry), and hyoid bone position. We studied 13 supine, anesthetized, tracheostomized, spontaneously breathing adult male New Zealand White rabbits. Graded MA was applied from 0 to ∼4.5 mm. ETP was measured at six locations distributed throughout three UA regions: tongue, hyoid, and epiglottis. Axial computed tomography images of the UA (nasal choanae to glottis) were acquired and used to measure lumen geometry (UA length; regional cross-sectional area) and hyoid displacement. MA resulted in nonuniform decreases in ETP (greatest at tongue region), ranging from -0.11 (-0.15 to -0.06) to -0.82 (-1.09 to -0.54) cmH2O/mm MA [linear mixed-effects model slope (95% confidence interval)], across all sites. UA length decreased by -0.5 (-0.8 to -0.2) %/mm accompanied by nonuniform increases in cross-sectional area (greatest at hyoid region) ranging from 7.5 (3.6-11.4) to 18.7 (14.9-22.5) %/mm. The hyoid bone was displaced in a cranial-anterior direction by 0.42 (0.36-0.44) mm/mm MA. In summary, MA results in nonuniform changes in peripharyngeal tissue pressure distributions and lumen geometry. Displacement of the hyoid bone with MA may play a pivotal role in redistributing applied MA loads, thus modifying tissue stress/deformation distributions and determining resultant UA geometry outcomes. PMID:25505028

  6. A method for estimating gestational age of fetal remains based on long bone lengths.

    PubMed

    Carneiro, Cristiana; Curate, Francisco; Cunha, Eugénia

    2016-09-01

    The estimation of gestational age (GA) in fetal human remains is important in forensic settings, particularly to assess fetal viability, in addition to often being the only biological profile parameter that can be assessed with some accuracy for non-adults. The length of long bone diaphysis is one of the most frequently used methods for fetal age estimation. The main objective of this study was to present a simple and objective method for estimating GA based on the measurements of the diaphysis of the femur, tibia, fibula, humerus, ulna, and radius. Conventional least squares regression equations (classical and inverse calibration approaches) and quick reference tables were generated. A supplementary objective was to compare the performance of the new formulae against previously published models. The sample comprised 257 fetuses (136 females and 121 males) with known GA (between 12 and 40 weeks) and was selected based on clinical and pathological information. All measurements were performed on radiographic images acquired in anonymous clinical autopsy records from spontaneous and therapeutic abortions in two Portuguese hospitals. The proposed technique is straightforward and reproducible. The models for the GA estimation are exceedingly accurate and unbiased. Comparisons between inverse and classical calibration show that both perform exceptionally well, with high accuracy and low bias. Also, the newly developed equations generally outperform earlier methods of GA estimation in forensic contexts. Quick reference tables for each long bone are now available. The obtained models for the estimation of gestational age are of great applicability in forensic contexts. PMID:27251047

  7. A CAD system and quality assurance protocol for bone age assessment utilizing digital hand atlas

    NASA Astrophysics Data System (ADS)

    Gertych, Arakadiusz; Zhang, Aifeng; Ferrara, Benjamin; Liu, Brent J.

    2007-03-01

    Determination of bone age assessment (BAA) in pediatric radiology is a task based on detailed analysis of patient's left hand X-ray. The current standard utilized in clinical practice relies on a subjective comparison of the hand with patterns in the book atlas. The computerized approach to BAA (CBAA) utilizes automatic analysis of the regions of interest in the hand image. This procedure is followed by extraction of quantitative features sensitive to skeletal development that are further converted to a bone age value utilizing knowledge from the digital hand atlas (DHA). This also allows providing BAA results resembling current clinical approach. All developed methodologies have been combined into one CAD module with a graphical user interface (GUI). CBAA can also improve the statistical and analytical accuracy based on a clinical work-flow analysis. For this purpose a quality assurance protocol (QAP) has been developed. Implementation of the QAP helped to make the CAD more robust and find images that cannot meet conditions required by DHA standards. Moreover, the entire CAD-DHA system may gain further benefits if clinical acquisition protocol is modified. The goal of this study is to present the performance improvement of the overall CAD-DHA system with QAP and the comparison of the CAD results with chronological age of 1390 normal subjects from the DHA. The CAD workstation can process images from local image database or from a PACS server.

  8. Pore network microarchitecture influences human cortical bone elasticity during growth and aging.

    PubMed

    Bala, Yohann; Lefèvre, Emmanuelle; Roux, Jean-Paul; Baron, Cécile; Lasaygues, Philippe; Pithioux, Martine; Kaftandjian, Valérie; Follet, Hélène

    2016-10-01

    Cortical porosity is a major determinant of bone strength. Haversian and Volkmann׳s canals are׳seen' as pores in 2D cross-section but fashion a dynamic network of interconnected channels in 3D, a quantifiable footprint of intracortical remodeling. Given the changes in bone remodeling across life, we hypothesized that the 3D microarchitecture of the cortical pore network influences its stiffness during growth and ageing. Cubes of cortical bone of 2 mm side-length were harvested in the distal 1/3 of the fibula in 13 growing children (mean age±SD: 13±4 yrs) and 16 adults (age: 75±13 yrs). The cubes were imaged using desktop micro-CT (8.14µm isotropic voxel size). Pores were segmented as a solid to assess pore volume fraction, number, diameter, separation, connectivity and structure model index. Elastic coefficients were derived from measurements of ultrasonic bulk compression and shear wave velocities and apparent mass density. The pore volume fraction did not significantly differ between children and adults but originates from different microarchitectural patterns. Compared to children, adults had 42% (p=0.033) higher pore number that were more connected (Connective Density: +205%, p=0.001) with a 18% (p=0.007) lower pore separation. After accounting for the contribution of pore volume fraction, axial elasticity in traction-compression mode was significantly correlated with better connectivity in growing children and with pore separation among adults. The changes in intracortical remodeling across life alter the distribution, size and connectedness of the channels from which cortical void fraction originates. These alterations in pore network microarchitecture participate in changes in compressive and shear mechanical behavior, partly in a porosity-independent manner. The assessment of pore volume fraction (i.e., porosity) provides only a limited understanding of the role of cortical void volume fraction in its mechanical properties. PMID:27389322

  9. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  10. Age and Skeletal Sites Affect BMP-2 Responsiveness of Human Bone Marrow Stromal Cells

    PubMed Central

    Osyczka, Anna M.; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O.

    2010-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be partly due to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  11. Higher Doses of Bisphosphonates Further Improve Bone Mass, Architecture, and Strength but Not the Tissue Material Properties in Aged Rats

    PubMed Central

    Shahnazari, Mohammad; Yao, Wei; Dai, WeiWei; Wang, Bob; Ionova-Martin, Sophi S.; Ritchie, Robert O.; Heeren, Daniel; Burghardt, Andrew J.; Nicolella, Daniel P.; Kimiecik, Michael G.; Lane, Nancy E.

    2010-01-01

    We report the results of a series of experiments designed to determine the effects of ibandronate (Ibn) and risedronate (Ris) on a number of bone quality parameters in aged osteopenic rats to explain how bone material and bone mass may be affected by the dose of bisphosphonates (BP) and contribute to their anti-fracture efficacy. Eighteen-month old female rats underwent either ovariectomy or sham surgery. The ovariectomized (OVX) groups were left untreated for 2 months to develop osteopenia. Treatments started at 20 months of age as follows: sham and OVX control (treated with saline), OVX+risedronate 30 and 90 (30 or 90 μg/kg/dose), and OVX+ibandronate 30 and 90 (30 or 90 μg/kg/dose). The treatments were given monthly for four months by subcutaneous injection. At sacrifice at 24 months of age the 4th lumbar vertebra was used for μCT scans (bone mass, architecture, and degree of mineralization of bone, DMB) and histomorphometry, and the 6th lumbar vertebra, tibia, and femur were collected for biomechanical testing to determine bone structural and material strength, cortical fracture toughness, and tissue elastic modulus. The compression testing of the vertebral bodies (LVB6) was simulated using finite-element analysis (FEA) to also estimate the bone structural stiffness. Both Ibn and Ris dose-dependently increased bone mass and improved vertebral bone microarchitecture and mechanical properties compared to OVX control. Estimates of vertebral maximum stress from FEA were correlated with vertebral maximum load (r=0.5, p<0.001) and maximum stress (r=0.4, p<0.005) measured experimentally. Tibial bone bending modulus and cortical strength increased compared to OVX with both BP but no dose-dependent effect was observed. DMB and elastic modulus of trabecular bone were improved with Ibn30 compared to OVX but were not affected in other BP-treated groups. DMB of tibial cortical bone showed no change with BP treatments. The fracture toughness examined in midshaft femurs did

  12. Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells

    PubMed Central

    Kretlow, James D; Jin, Yu-Qing; Liu, Wei; Zhang, Wen Jie; Hong, Tan-Hui; Zhou, Guangdong; Baggett, L Scott; Mikos, Antonios G; Cao, Yilin

    2008-01-01

    Background Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another. Results Differences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors. Conclusion Both increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use. PMID:18957087

  13. Soft tissue aneurysmal bone cyst: a rare case in a middle aged patient

    PubMed Central

    Baker, Kevin S; Gould, Elaine S; Patel, Hiten B; Hwang, Sonya J

    2015-01-01

    Soft tissue aneurysmal bone cyst is a rare entity, with about 20 cases reported in literature, only 3 of which are in patients over 40 years of age. We present a case of a 41 year old Latin American female who presented for evaluation of atraumatic chest pain with radiation to the left shoulder. Her initial workup was negative, including radiographic imaging of the chest and left shoulder. 4 months later, she presented to her orthopedic surgeon with a palpable mass and mild left shoulder pain. Radiographs acquired at that time demonstrated a 7.0 × 5.5 × 6.7 cm mass with rim calcification in the region of the upper triceps muscle. Subsequent CT imaging showed central areas of hypodensity and thin septations, a few of which were calcified. MR evaluation showed hemorrhagic cystic spaces with multiple fluid-fluid levels and enhancing septations. Surgical biopsy was performed and pathology was preliminarily interpreted as cystic myositis ossificans, however on final review the diagnosis of soft tissue aneurysmal bone cyst was made. The lesion was then surgically excised and no evidence of recurrence was seen on a 3 year post-op radiograph. Following description of our case, we conduct a literature review of the imaging characteristics, diagnosis, and treatment of soft tissue aneurysmal bone cyst. PMID:25926918

  14. Anti-Aging Effects of the Hanwoo Leg Bone, Foot and Tail Infusions (HLI, HFI and HTI) on Skin Fibroblast.

    PubMed

    Seol, Ja Young; Yoon, Ji Young; Jeong, Hee Sun; Joo, Nami; Choi, Soon Young

    2016-01-01

    Many researchers revealed that collagen contribute to maintaining the skin's elasticity and inhibit wrinkling of skin. Korean native cattle (Hanwoo) bone (leg bone, foot and tail) infusion contains the various inorganic materials, collagen and chondroitin sulfate. All of this, a large quantity of collagen is included in Hanwoo infusion. Therefore, this study emphasized on the effects of collagen in the Hanwoo bone infusion. For the first time, Hanwoo bone infusions were directly added to the media of Human Dermal Fibroblast (NHDF-c) to test anti-aging effects. First, it was identified that growth rate of skin fibroblast was increased. Furthermore, the Hanwoo bone infusion increased a 50% of fibroblast collagen synthesis. Also, suppression of skin fibroblast aging was confirmed by treatment Hanwoo bone infusion. In conclusion, this study demonstrates the effects of infusion made from Hanwoo leg bone, foot and tail on anti-aging, wrinkle inhibiting and skin fibroblast elasticity maintaining. Therefore, this study identified that traditional infusion has effects that are good for skin elasticity. PMID:27194933

  15. Anti-Aging Effects of the Hanwoo Leg Bone, Foot and Tail Infusions (HLI, HFI and HTI) on Skin Fibroblast

    PubMed Central

    Yoon, Ji Young; Jeong, Hee Sun; Joo, Nami

    2016-01-01

    Many researchers revealed that collagen contribute to maintaining the skin’s elasticity and inhibit wrinkling of skin. Korean native cattle (Hanwoo) bone (leg bone, foot and tail) infusion contains the various inorganic materials, collagen and chondroitin sulfate. All of this, a large quantity of collagen is included in Hanwoo infusion. Therefore, this study emphasized on the effects of collagen in the Hanwoo bone infusion. For the first time, Hanwoo bone infusions were directly added to the media of Human Dermal Fibroblast (NHDF-c) to test anti-aging effects. First, it was identified that growth rate of skin fibroblast was increased. Furthermore, the Hanwoo bone infusion increased a 50% of fibroblast collagen synthesis. Also, suppression of skin fibroblast aging was confirmed by treatment Hanwoo bone infusion. In conclusion, this study demonstrates the effects of infusion made from Hanwoo leg bone, foot and tail on anti-aging, wrinkle inhibiting and skin fibroblast elasticity maintaining. Therefore, this study identified that traditional infusion has effects that are good for skin elasticity. PMID:27194933

  16. Association between Homocysteine and Bone Mineral Density according to Age and Sex in Healthy Adults

    PubMed Central

    Kim, Joo Il; Moon, Ji Hyun; Chung, Hye Won; Kong, Mi Hee

    2016-01-01

    Background There are several studies about the relationship between serum homocysteine levels and bone mineral density (BMD), but the results are varied, and the studies are limited in Korea. In our study, the relationship between serum homocysteine levels and BMD by part according to age and sex is investigated. Methods From March 2012 to July 2015, the 3,337 healthy adults who took a medical examination were recruited. Subjects filled in the self-recording type questionnaire and physical examination, blood test, BMD of lumbar spine and femur were measured. After sorting by aging (≤49 year old, 50-59 year old, ≥60 year old) and sex, the results were adjusted with age and body mass index (BMI) and the relationship between serum homocysteine levels and BMD by lumbar spine and femur was analyzed by multiple regression analysis. Results As results of analysis, with the adjustment with age and BMI, all age groups of men had no significant relationship between log-converted serum homocysteine levels and BMD. In women aged under 50, there were significantly negative relationships at lumbar spine (β=-0.028, P=0.038), femur neck (β=-0.062, P=0.001), and total hip (β=-0.076, P<0.001), but there was no significant relationship in other age groups (50-59 year old and ≥60 year old). Conclusions As the serum homocysteine levels increased in women aged under 50, BMD of the lumbar spine and femur decreased, and correlations between homocysteine and BMD were different by sex and age. PMID:27622176

  17. Growth and aging of proximal femoral bone: a study with women spanning three generations.

    PubMed

    Wang, Qin; Chen, Decai; Cheng, Shu Mei; Nicholson, Patrick; Alen, Markku; Cheng, Sulin

    2015-03-01

    Osteoporotic hip fracture is a serious clinical event associated with high morbidity and mortality. Understanding femoral growth patterns is important for promoting bone health in the young and preventing fractures in later life. In this study, growth patterns of areal bone mineral density (aBMD) and geometric properties of the proximal femur were measured by dual-energy X-ray absorptiometry. They were studied in 251 girls from premenarche (11.2 ± 0.7 years) to late adolescence (18.3 ± 1.1 years) and compared with their premenopausal mothers (n = 128, aged 44.9 ± 4.1 years) and postmenopausal grandmothers (n = 128, aged 70.0 ± 6.3 years). Hip axis length (HAL) was the first to reach peak growth velocity (-10.5 months before menarche), followed by neck diameter (ND) and neck cross-sectional area (CSA), (-7.1 and -4.1 months before menarche, respectively). Both neck-shaft angle (NSA) and aBMD of neck and total hip peaked at menarche. At 18 years (7-year follow-up), girls already had higher femoral neck aBMD but similar HAL and NSA compared with their mothers. Grandmothers had the longest HAL, narrowest NSA, widest ND but lowest aBMD and CSA. Hip strength index (HSI), an index of femoral neck strength during a fall, dropped rapidly after menarche in girls but thereafter remained relatively constant. Grandmothers had lower HSI than either mothers or girls. In conclusion, differences in proximal femoral bone mass and structure in adulthood are largely established before menarche, indicating that heritable factors are responsible for most of the individual variance. The development of geometric properties precedes aBMD in puberty, resulting in relatively constant hip strength after menarche. This asynchronous growth leads to adaptation of bone strength to the imposed loads, avoiding fractures in a biologically efficient manner. Both deterioration of aBMD and inadequate compensatory change in bone geometry after menopause contribute to the

  18. Bone marrow declines as a site of B-cell precursor differentiation with age: relationship to thymus involution.

    PubMed Central

    Ben-Yehuda, A; Szabo, P; Dyall, R; Weksler, M E

    1994-01-01

    The rearrangement of immunoglobulin genes in B-lymphocyte precursors requires the expression of the recombination activating genes (Rag), which leads to the generation of a highly diverse B-cell repertoire. We can use the level of Rag-1 mRNA in the bone marrow as an index of its capacity to support the maturation of B lymphocytes as all detectable bone marrow Rag-1 mRNA is expressed by B-cell precursors. In mouse bone marrow, Rag-1 mRNA increases during the first 2 months of life to reach its maximal level at 2 months of age. This level is maintained until 5 months of age and thereafter declines to a minimum level by 10 months of age. Thus, bone marrow Rag-1 mRNA is highest at the time when thymic function is maximal in euthymic mice. An association between thymic activity and bone marrow Rag-1 gene expression was supported by showing a low level of bone marrow Rag-1 mRNA in athymic nude mice at an age when this gene is maximally expressed in euthymic mice. Another characteristic of B cells in nude mice is their preferential rearrangement of diversity region (D)-proximal heavy-chain variable region (VH) genes. We demonstrated that injection of syngeneic splenic T cells into nude mice not only stimulates an increase in Rag-1 mRNA in their bone marrow B-cell precursors but also restores their random use of VH genes. Most interestingly, injection of supernatant medium from phytohemagglutinin-activated splenic T-cell cultures from young euthymic mice also induces both Rag-1 mRNA in bone marrow B-cell precursors and random use of VH genes. These findings suggest that thymic function can regulate both Rag-1 gene expression and VH gene use by bone marrow B-cell precursors. Images PMID:7991570

  19. Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

    PubMed

    Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

    2015-12-01

    Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. PMID:26142929

  20. The effects of strength training and raloxifene on bone health in aging ovariectomized rats.

    PubMed

    Stringhetta-Garcia, Camila Tami; Singulani, Monique Patrício; Santos, Leandro Figueiredo; Louzada, Mário Jefferson Quirino; Nakamune, Ana Cláudia Stevanato; Chaves-Neto, Antonio Hernandes; Rossi, Ana Cláudia; Ervolino, Edilson; Dornelles, Rita Cássia Menegati

    2016-04-01

    The aim of this study was to investigate the effects of strength training (ST) and raloxifene (Ral), alone or in combination, on the prevention of bone loss in an aging estrogen-deficient rat model. Aging Wistar female rats were ovariectomized at 14months and allocated to four groups: (1) non-trained and treated with vehicle, NT-Veh; (2) strength training and treated with vehicle, ST-Veh; (3) non-trained and treated with raloxifene, NT-Ral; and (4) strength training and treated with raloxifene, ST-Ral. ST was performed on a ladder three times per week and Ral was administered daily by gavage (1mg/kg/day), both for 120days. Areal bone mineral density (aBMD), strength, microarchitecture, and biomarkers (osteocalcin, OCN; osteoprotegerin, OPG; and tartrate-resistant acid phosphatase, TRAP) were assessed. Immunohistochemistry was performed for runt-related transcription factor 2 (RUNX2), osterix (OSX), OCN, OPG, TRAP, and receptor activator of nuclear factor kappa-B ligand (RANKL). The rats that performed ST (ST-Veh) or were treated with Ral (NT-Ral) showed significant improvements in aBMD (p=0.001 and 0.004), bone strength (p=0.001), and bone microarchitecture, such as BV/TV (%) (p=0.001), BS/TV (mm(2)/mm(3)) (p=0.023 and 0.002), Conn.Dn (1/mm(3)) (p=0.001), Tb.N (1/mm) (p=0.012 and 0.011), Tb.Th (1/mm) (p=0.001), SMI (p=0.001 and 0.002), Tb.Sp (p=0.001), and DA (p=0.002 and 0.007); there was also a significant decrease in plasma levels of OCN (p=0.001 and 0.002) and OPG (p=0.003 and 0.014), compared with animals in the NT-Veh group. Ral, with or without ST, promoted an increased immunolabeling pattern for RUNX2 (p=0.0105 and p=0.0006) and OSX (p=0.0105), but a reduced immunolabeling pattern for TRAP (p=0.0056) and RANKL (p=0.033 and 0.004). ST increased the immunolabeling pattern for RUNX2 (p=0.0105), and association with Ral resulted in an increased immunolabeling pattern for OPG (p=0.0034) and OCN (p=0.0024). In summary, ST and Ral administration in aged, estrogen

  1. γ-Secretase inhibitor reverts the Notch signaling attenuation of osteogenic differentiation in aged bone marrow mesenchymal stem cells.

    PubMed

    Tang, Zhaolong; Wei, Junjun; Yu, Yunbo; Zhang, Jiankang; Liu, Lei; Tang, Wei; Long, Jie; Zheng, Xiaohui; Jing, Wei

    2016-04-01

    The age-related changes in cell viability and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) play pivotal roles in the fracture healing process, especially in geriatric individuals. This study was designed to explore the age-related changes in murine BMSCs and the regulation of osteogenic differentiation in aged BMSCs in vitro. Notch signaling pathway took part in the regulation of osteogensis, while the relationship between Notch and the osteogenic differentiation in aged BMSCs has not been reported yet. BMSCs harvested from the bone marrow of young, adult, and aged C57BL/6 mice were cultured in osteogenic and adipogenic differentiation media. Histochemical staining results indicated that the osteogenic ability of BMSCs gradually decreased with aging, whereas the adipogenic ability increased. Cell activity assays showed that the proliferative and migrated capacity did not decline with aging significantly. According to real-time PCR and Western blotting results, the aged cells exhibited higher Notch signaling expression level than the younger ones did. After the aged BMSCs being treated with γ-secretase inhibitor, however, Notch activity was changed and the aging-imparied osteogenic ability reverted to a normal level. This study demonstrated that the decreased bone formation capacity in aged BMSCs had relationship with the transdifferentiation between osteogenesis and adipogenesis, which would be regulated by Notch signaling pathway and the attenuated osteogenesis in aged BMSCs could be promoted when the inhibition of Notch pathway. PMID:26801333

  2. Normative Data for Bone Mass in Healthy Term Infants from Birth to 1 Year of Age

    PubMed Central

    Gallo, Sina; Vanstone, Catherine A.; Weiler, Hope A.

    2012-01-01

    For over 2 decades, dual-energy X-ray absorptiometry (DXA) has been the gold standard for estimating bone mineral density (BMD) and facture risk in adults. More recently DXA has been used to evaluate BMD in pediatrics. However, BMD is usually assessed against reference data for which none currently exists in infancy. A prospective study was conducted to assess bone mass of term infants (37 to 42 weeks of gestation), weight appropriate for gestational age, and born to healthy mothers. The group consisted of 33 boys and 26 girls recruited from the Winnipeg Health Sciences Center (Manitoba, Canada). Whole body (WB) as well as regional sites of the lumbar spine (LS 1–4) and femur was measured using DXA (QDR 4500A, Hologic Inc.) providing bone mineral content (BMC) for all sites and BMD for spine. During the year, WB BMC increased by 200% (76.0 ± 14.2 versus 227.0 ± 29.7 g), spine BMC by 130% (2.35 ± 0.42 versus 5.37 ± 1.02 g), and femur BMC by 190% (2.94 ± 0.54 versus 8.50 ± 1.84 g). Spine BMD increased by 14% (0.266 ± 0.044 versus 0.304 ± 0.044 g/cm2) during the year. This data, representing the accretion of bone mass during the first year of life, is based on a representative sample of infants and will aid in the interpretation of diagnostic DXA scans by researchers and health professionals. PMID:23091773

  3. FTIR-I Compositional Mapping of the Cartilage-to-Bone Interface as a Function of Tissue Region and Age

    PubMed Central

    Khanarian, Nora T; Boushell, Margaret K; Spalazzi, Jeffrey P; Pleshko, Nancy; Boskey, Adele L; Lu, Helen H

    2016-01-01

    Soft tissue-to-bone transitions, such as the osteochondral interface, are complex junctions that connect multiple tissue types and are critical for musculoskeletal function. The osteochondral interface enables pressurization of articular cartilage, facilitates load transfer between cartilage and bone, and serves as a barrier between these two distinct tissues. Presently, there is a lack of quantitative understanding of the matrix and mineral distribution across this multitissue transition. Moreover, age-related changes at the interface with the onset of skeletal maturity are also not well understood. Therefore, the objective of this study is to characterize the cartilage-to-bone transition as a function of age, using Fourier transform infrared spectroscopic imaging (FTIR-I) analysis to map region-dependent changes in collagen, proteoglycan, and mineral distribution, as well as collagen organization. Both tissue-dependent and age-related changes were observed, underscoring the role of postnatal physiological loading in matrix remodeling. It was observed that the relative collagen content increased continuously from cartilage to bone, whereas proteoglycan peaked within the deep zone of cartilage. With age, collagen content across the interface increased, accompanied by a higher degree of collagen alignment in both the surface and deep zone cartilage. Interestingly, regardless of age, mineral content increased exponentially across the calcified cartilage interface. These observations reveal new insights into both region- and age-dependent changes across the cartilage-to-bone junction and will serve as critical benchmark parameters for current efforts in integrative cartilage repair. PMID:24839262

  4. Apocynin suppression of NADPH oxidase reverses the aging process in mesenchymal stem cells to promote osteogenesis and increase bone mass

    PubMed Central

    Sun, Jinlong; Ming, Leiguo; Shang, Fengqing; Shen, Lijuan; Chen, Jihua; Jin, Yan

    2015-01-01

    Because of the reduced potential for osteogenesis in aging bone marrow stromal cells, the balance of bone metabolism becomes disrupted, leading to various bone diseases. An increase in reactive oxygen species has been determined to be one of the key factors that accelerates the aging process in BMSCs. In these cells, increased expression of NADPH oxidases is the major source of ROS. In the current study, we suppressed the expression of NOX using apocynin, an effective antioxidant and free radical scavenger, and the results showed that aging BMSCs exhibited an enhanced potential for osteogenesis. The expression of potential key targets influencing this reversal was evaluated using qRT-PCR, and the expression of p53 was shown to be reduced with the suppression of NOX. We speculate that this may be one of the major reasons for the reversal of the aging process. We also examined the effect of apocynin in vivo, and the results showed that in SAMP6 mice, bone mineral density and total bone volume were increased after 3 months of apocynin treatment. In conclusion, our results demonstrate that in aging BMSCs, suppression of NADPH oxidase by apocynin partially reverses the aging process and enhances osteogenic potential. PMID:26686764

  5. Biopsy Needle Advancement during Bone Marrow Aspiration Increases Mesenchymal Stem Cell Concentration

    PubMed Central

    Peters, Anne E.; Watts, Ashlee E.

    2016-01-01

    Point-of-care kits to concentrate bone marrow (BM)-derived mesenchymal stem cells (MSCs) are used clinically in horses. A maximal number of MSCs per milliliter of marrow aspirated might be desired prior to use of a point-of-care system to concentrate MSCs. Our objective was to test a method to increase the number of MSCs per milliliter of marrow collected. We collected two BM aspirates using two different collection techniques from 12 horses. The first collection technique was to aspirate BM from a single site without advancement of the biopsy needle. The second collection technique was to aspirate marrow from multiple sites within the same sternal puncture by advancing the needle 5 mm three times for BM aspiration from four sites. Numbers of MSCs in collected BM were assessed by total nucleated cell count of BM after aspiration, total colony-forming unit-fibroblast (CFU-F) assay, and total MSC number at each culture passage. The BM aspiration technique of four needle advancements during BM aspiration resulted in higher initial nucleated cell counts, more CFU-Fs, and more MSCs at the first passage. There were no differences in the number of MSCs at later passages. Multiple advancements of the BM needle during BM aspiration resulted in increased MSC concentration at the time of BM collection. If a point-of-care kit is used to concentrate MSCs, multiple advancements may result in higher MSC numbers in the BM concentrate after preparation by the point-of-care kit. For culture expanded MSCs beyond the first cell passage, the difference is of questionable clinical relevance. PMID:27014705

  6. Biopsy Needle Advancement during Bone Marrow Aspiration Increases Mesenchymal Stem Cell Concentration.

    PubMed

    Peters, Anne E; Watts, Ashlee E

    2016-01-01

    Point-of-care kits to concentrate bone marrow (BM)-derived mesenchymal stem cells (MSCs) are used clinically in horses. A maximal number of MSCs per milliliter of marrow aspirated might be desired prior to use of a point-of-care system to concentrate MSCs. Our objective was to test a method to increase the number of MSCs per milliliter of marrow collected. We collected two BM aspirates using two different collection techniques from 12 horses. The first collection technique was to aspirate BM from a single site without advancement of the biopsy needle. The second collection technique was to aspirate marrow from multiple sites within the same sternal puncture by advancing the needle 5 mm three times for BM aspiration from four sites. Numbers of MSCs in collected BM were assessed by total nucleated cell count of BM after aspiration, total colony-forming unit-fibroblast (CFU-F) assay, and total MSC number at each culture passage. The BM aspiration technique of four needle advancements during BM aspiration resulted in higher initial nucleated cell counts, more CFU-Fs, and more MSCs at the first passage. There were no differences in the number of MSCs at later passages. Multiple advancements of the BM needle during BM aspiration resulted in increased MSC concentration at the time of BM collection. If a point-of-care kit is used to concentrate MSCs, multiple advancements may result in higher MSC numbers in the BM concentrate after preparation by the point-of-care kit. For culture expanded MSCs beyond the first cell passage, the difference is of questionable clinical relevance. PMID:27014705

  7. The Relationship between Greater Pre-Pubertal Adiposity, Subsequent Age of Maturation and Bone Strength during Adolescence†

    PubMed Central

    Glass, Natalie A.; Torner, James C.; Letuchy, Elena M.; Burns, Trudy L.; Janz, Kathleen F.; Gilmore, Julie M. Eichenberger; Schlechte, Janet A.; Levy, Steven M.

    2016-01-01

    This longitudinal study investigated whether greater pre-pubertal adiposity was associated with subsequent timing of maturation and bone strength during adolescence in 135 girls and 123 boys participating in the Iowa Bone Development Study. Greater adiposity was defined using BMI data at age 8 years to classify participants as overweight (OW, ≥85th percentile for age and sex) or healthy-weight, HW). Maturation was defined as the estimated age of peak height velocity (PHV) based on a series of cross-sectional estimates. Measurements were taken at ages 11, 13, 15 and 17 years for estimates of body composition by DXA, bone compression (bone strength index) and torsion strength (polar strength-strain index) at the radius and tibia by pQCT, and femoral neck bending strength (section modulus) by hip structural analysis. Bone strength in OW versus HW were evaluated by fitting sex-specific linear mixed models that included centered age (visit age – grand mean age of cohort) as the time variable and adjusted for change in fat mass, and limb length in Model 1. Analyses were repeated using biological age (visit ageage PHV) as the time variable for Model 1 with additional adjustment for lean mass in Model 2. BMI was negatively associated with age of maturation (p<0.05). OW versus HW girls had significantly greater bone strength (p<0.001) in Model 1, while OW versus HW boys had significantly greater bone strength (p<0.001) at the tibia and femoral neck, but not radius (p>0.05). Analyses were repeated using biological age, which yielded reduced parameter estimates for girls but similar results for boys (Model 1.) Differences were no longer present following adjustment for lean mass (Model 2) in girls (p>0.05) while differences at the tibia were sustained in boys (p<0.05). These findings demonstrate sex- and site-specific differences in the associations between adiposity, maturation and bone strength. PMID:26861036

  8. [EFFECT OF MELATONIN ON AGE-RELATED DYNAMICS OF THE REACTIVE PROPERTIES OF BONE TISSUE].

    PubMed

    Levashov, M I; Chaka, E G; Yanko, R V; Zamorska, T M

    2015-10-01

    The effect of melatonin (MT) on the bone tissue (BT) reactive properties was investigated among 80 male Wistar rats at the age of 3, 9, 12 and 16 months. The reactive properties of BT were judged by its ability to polarization under the influence of the alternating electric current. The value of reactance at the frequency of maximum polarization was used as the indicator of BT reactivity. Experimental animals received daily melatonin (Unipharm Inc., USA) at the rate of 1 mg/kg of body mass for 28 days. Freshly isolated femurs of rats served as a material for investigation. Introduction of MT to rats resulted in a significant increase in bone mass and polarization properties of BT. However, the clear tendency to increase the reactance not more than 2.2 % (p < 0.1) compared with the control group among the 3-month old rats were observed, and the increasing the reactance among 9 and 12-month old rats were 6.3% and 12.1% (p < 0.1), respectively. Most significantly, the reactance increased by 21.8% (p < 0.05) among 15-month old animals. Thus the introduction of MT increased the reactivity of BT. This effect had a clear dependence on the age and appeared more among older animals. PMID:26827497

  9. Predictors of Bone Mineral Density in African-American and Caucasian College-Aged Women

    PubMed Central

    Johnson, Andrea K.; Ford, M. Allison; Jones, Tamekia L.; Nahar, Vinayak K.; Hallam, Jeffrey S.

    2015-01-01

    Background: Research regarding risk factors and prevalence of low bone mineral density (BMD) among African-American and Caucasian college-aged women are limited. The objective of this cross-sectional study was to determine if selected predictors of BMD in African-American and Caucasian college-aged women differ by race. Methods: A total of 101 local African-American (n=50) and Caucasian (n=51) females, ages 18 to 30 years, were in this study. All data were collected in the Bone Density and Body Composition Laboratory. BMD was measured using DXA technology. Race, family history of osteoporosis, BMI, current physical activity, osteoporosis knowledge, length of time on oral contraceptives, age at menarche and calcium intake were included in the multiple regression analyses with spinal and femoral BMD as dependent variables. Results: Overall, 38.6% had low spinal BMD and 7.9% had low femoral BMD. BMI (β=0.073, R2 = .148, P = .001, 95% CI [0.030, 0.116]) and current physical activity (β=0.071, R2 = .148, P = .017, 95% CI [0.013, 0.129]) were the only variables that were statistically significant in predicting spinal BMD. BMI (β=0.056, R2 = .13, P = .010, 95% CI [0.014, 0.098]) and current physical activ-ity (β=0.078, R2 = .13, P = .007, 95% CI [0.022, 0.134]) were also the only varia-bles that were statistically significant in predicting femoral BMD. Race was not a significant predictor of spinal or femoral BMD. Conclusion: It is imperative for both African-American and Caucasian women to engage in osteoporosis-preventive behaviors. PMID:26000242

  10. Evaluation of the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing.

    PubMed

    Gnudi, S; Mongiorgi, R; Figus, E; Bertocchi, G

    1990-12-01

    To evaluate the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing, three groups of women were studied by computerized bone densitometry at the radius mid-point and at the distal point, modified according to the Abwrey technique. All women were in apparent good health and never had estrogen therapy. In the first group there were 64 women aged between 30 and 50 who were ovariectomized between 25 and 35 years of age. The second group was made up of 309 women between 50 and 55 years. In the third group there were 136 women aged 30-50 with normal ovaric function. The ordinary functions of linear polynomial regression were used to describe the variations in density with age. The percentage of postmenopausal bone loss was determined by calculating the BMC value at the start of the menopause and again twenty years later, according to the linear regression equation of postmenopausal period of each group of women in the study. The women who had natural menopause showed an average bone loss per year of 1.63% at the mid radius and 1.0% at the distal point. The ovariectomized women had an average loss of 0.85% at the mid point and 0.66% at the distal point. No significant decrease of bone mass was found before menopause. From a comparison between the two groups of women with analogous periods of menopause, it comes out that, during the first 20 years of natural menopause, estrogen deficiency is responsible for 52.5%-66.4% of the bone mineral loss, the remaining amount being attributable to other causes, connected with ageing. Estrogen deficiency is therefore, the principal factor causing bone mineral loss in natural menopause. PMID:2100526

  11. Evaluation of an injectable bone substitute (betaTCP/hydroxyapatite/hydroxy-propyl-methyl-cellulose) in severely osteopenic and aged rats.

    PubMed

    Blouin, S; Moreau, M F; Weiss, P; Daculsi, G; Baslé, M F; Chappard, D

    2006-09-01

    The use of injectable biomaterials is of interest in osteoporotic patients to locally restore bone mass in sites at risk of fracture. An injectable bone substitute (IBS1 made of betaTCP/hydroxyapatite as a calcium phosphate substitute and hydroxy-propyl-methyl-cellulose as a polymer carrier) was used in a severely osteopenic rat model obtained by combining orchidectomy (ORX) and disuse (paralysis induced by botulinum toxin - BTX). Fifty-six aged male rats were randomized into three groups: 18 were SHAM operated; 38 were ORX and BTX injected in the right hindlimb; they constituted the OP (osteoporotic) group. One month after ORX-BTX surgery, 20 of these OP rats received a IBS1 injection in the right femur (OP-IBS1 rats). Animals were studied at the time of IBS1 injection 1 month post ORX-BTX (M1), 1 month (M2) and 2 months (M3) after IBS1 injection. Bone mass (BV/TV) and microarchitectural parameters were measured by microCT. BV/TV was decreased after ORX-BTX; ORX and BTX had cumulative effects on bone loss (differences maximized on the right femur). BV/TV (combining the volume of both bone and material in OP-IBS1 rats) was elevated at M1 but decreased at M2. Marked bone formation was found onto the biomaterial granules but bone had a woven texture. A marked increase in the number of nonosteoclastic TRAcP+ cells was found in the implanted area. IBS1 induced new bone formation shortly after implantation but both IBS1 and woven bone were resorbed without inducing lamellar bone. Biomaterial trials must be conducted with long-term implantation periods, in aged osteoporotic animals. PMID:16739169

  12. Age estimation in the Mediterranean bottlenose dolphin Tursiops truncatus(Montagu 1821) by bone density of the thoracic limb

    PubMed Central

    Butti, Camilla; Corain, Livio; Cozzi, Bruno; Podestà, Michela; Pirone, Andrea; Affronte, Marco; Zotti, Alessandro

    2007-01-01

    The determination of age is an important step in defining the life history traits of individuals and populations. Age determination of odontocetes is mainly based on counting annual growth layer groups in the teeth. However, this useful method is always invasive, requiring the cutting of at least one tooth, and sometimes the results are difficult to interpret. Based on the concept that bone matrix is constantly deposited throughout life, we analysed the bone mineral density of the arm and forearm of a series of bottlenose dolphins (Tursiops truncatus, Montagu 1821) stranded along the Italian coast of the Adriatic Sea or maintained in confined waters. The bone mineral density values we obtained were evaluated as possible age predictors of the Mediterranean population of this species, considering age as determined by counting growth layer groups in sections of the teeth and the total body length of the animal as references. Comparisons between left and right flipper showed no difference. Our results show that bone mineral density values of the thoracic limb are indeed reliable age predictors in Tursiops truncatus. Further investigations in additional odontocete species are necessary to provide strong evidence of the reliability of bone mineral density as an indicator of growth and chronological wear and tear in toothed-whales. PMID:17850286

  13. Lifecourse study of bone health at age 49–51 years: the Newcastle thousand families cohort study

    PubMed Central

    Pearce, M.; Birrell, F.; Francis, R.; Rawlings, D.; Tuck, S.; Parker, L.

    2005-01-01

    Objective: To quantify the direct and indirect effects of fetal (position in family, weight, and social class at birth), childhood (breast feeding, growth, infections, and social class in childhood, age at menarche), and adult life (social class, alcohol consumption, smoking, diet, reproductive history, exercise, hormone replacement therapy use), and adult size (height, weight) on bone health at age 49–51 years, as measured by bone mineral density, total scanned bone area of the hip and lumbar spine, and femoral neck shaft angle. Design: Follow up study of the Newcastle thousand families birth cohort established in 1947. Participants: 171 men and 218 women who attended for dual energy x ray absorptiometry scanning. Main results: Fetal life explained around 6% of variation in adult bone mineral density for men, but accounted for less than 1% for women. Adult lifestyle, including effects mediated through adult weight accounted for over 10% of variation in density for men and around 6% for women. Almost half of variation in bone area for men was explained by early life. However, most of this was mediated through achieved adult height and weight. In women, less than 5% of variation in bone area was accounted for by early life, after adjusting for adult size. Most of the variation in each of the indicators for both sexes was contributed either directly or indirectly by adult lifestyle and achieved adult height and weight. Conclusions: The effect of fetal life on bone health in adulthood seems to be mediated through achieved adult height. PMID:15911643

  14. Changes in the mineral density distribution in human bone with age: image analysis using backscattered electrons in the SEM.

    PubMed

    Reid, S A; Boyde, A

    1987-02-01

    We report a study to test the feasibility of studying mineral density distributions in bone using the backscattered electron signal in scanning electron microscopy. Samples were human sixth ribs ranging in age from 8 weeks to 59 years, embedded in polymethylmethacrylate (PMMA), cut, polished, and carbon coated. The proportions of pixels falling in a uniform set of gray level slices of the BSE signal were determined using a microcomputer-based image analysis system interfaced directly to the SEM. The amount of high-density bone gradually increased with age at the expense of low-density bone, and there was an associated compression of the range of the mineral density distribution. Age-related differences were noted between the density distributions in the outer and inner rib cortices. The distribution in the inner cortex in neonates was influenced by the inclusion of densely mineralized endochondral bone and cartilage trabeculae formed at the growth cartilage zone. In adults it appeared that greater bone turnover occurred in the outer cortex, perhaps reflecting a differential mechanical loading across the rib. The technique enabled rapid, unbiased discrimination between the bone of neonates, children, and adults. PMID:3455153

  15. The impact of age at death on the lag time of radiocarbon values in human bone.

    PubMed

    Ubelaker, Douglas H; Thomas, Christian; Olson, Jacqueline E

    2015-06-01

    Analysis of modern bomb-pulse radiocarbon in human bone offers data needed to interpret the post-mortem interval in skeletonized human remains recovered from forensic contexts. Radiocarbon analysis of different tissues with distinct rates of remodeling allows proper placement of the values on the modern bomb-curve. However, the lag time between the date of intercept on the curve and the actual death date is largely affected by the age at death. Published data on radiocarbon analysis of individuals of known age at death and death dates indicate that this lag time increases with age until about 60 years. The lag time documented for each decade of life can be used to compensate for this age-related factor and increase the accuracy of interpretation of the death date. While this method could be greatly improved by original research with a larger sample size, this study provides an adequate point from which to launch further investigations into the subject. PMID:25863698

  16. Lifelong physical activity in maintaining bone strength in older men and women of the Age, Gene/Environment Susceptibility–Reykjavik Study

    PubMed Central

    Lang, T.F.; Sigurdsson, G.; Eiriksdottir, G.; Sigurdsson, S.; Garcia, M.; Pajala, S.; Koster, A.; Yu, B.; Selwyn, B.J.; Taylor, W.C.; Kapadia, A.S.; Gudnason, V.; Launer, L.J.; Harris, T.B.

    2016-01-01

    Summary We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Associations of quantitative computerized tomography-acquired bone measures (vertebral and femoral) and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES– Reykjavik Study. Results conclude lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health later in life. Introduction Skeletal loading is thought to modulate the loss of bone in later life, and physical activity is a chief means of affecting bone strength by skeletal loading. Despite much discussion regarding lifelong versus early adulthood physical activity for preventing bone loss later in life, inconsistency still exists regarding how to maintain bone mass later in life (≥65 years). Methods We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Results The associations of quantitative computerized tomography-acquired vertebral and femoral bone measures and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES–Reykjavik Study. Conclusion Our findings conclude that lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health in the elderly. PMID:22234811

  17. Content of stromal precursor cells in heterotopic transplants of bone marrow in CBA mice of various ages.

    PubMed

    Gorskaya, Yu F; Kuralesova, A I; Shuklina, E Yu; Nesterenko, V G

    2002-02-01

    Efficiency of colony formation of stromal precursor cells in cultured bone marrow transplants from old (24 month) CBA mice implanted to young (2-month-old) mice almost 3-fold surpassed that in cultured transplants implanted to old recipients. The content of nucleated cells in bone marrow transplants from senescence accelerated mice SAMP increased more than 2-fold, if SAMR mice with normal aging rate were used as the recipients instead of SAMP mice. Bone marrow taken from old and young CBA mice endured the same number of transplantations if the recipient mice were of the same age (5 month). It was concluded that stromal tissue considerably changes with age and is under strict control of the body. PMID:12432868

  18. Revised Reference Curves for Bone Mineral Content and Areal Bone Mineral Density According to Age and Sex for Black and Non-Black Children: Results of the Bone Mineral Density in Childhood Study

    PubMed Central

    Kalkwarf, Heidi J.; Gilsanz, Vicente; Lappe, Joan M.; Oberfield, Sharon; Shepherd, John A.; Frederick, Margaret M.; Huang, Xiangke; Lu, Ming; Mahboubi, Soroosh; Hangartner, Thomas; Winer, Karen K.

    2011-01-01

    Context: Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ancestry to identify bone deficits. Objective: The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children. Design: The Bone Mineral Density in Childhood Study was a multicenter longitudinal study with annual assessments for up to 7 yr. Setting: The study was conducted at five clinical centers in the United States. Participants: Two thousand fourteen healthy children (992 males, 22% African-Americans) aged 5–23 yr participated in the study. Intervention: There were no interventions. Main Outcome Measures: Reference percentiles for BMC and aBMD of the total body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry for Black and non-Black children. Adjustment factors for height status were also calculated. Results: Extended reference curves for BMC and aBMD of the total body, total body less head, lumbar spine, total hip, femoral neck, and forearm for ages 5–20 yr were constructed relative to sex and age for Black and non-Black children. Curves are similar to those previously published for 7–17 year olds. BMC and aBMD values were greater for Black vs. non-Black children at all measurement sites. Conclusions: We provide here dual-energy x-ray absorptiometry reference data on a well-characterized cohort of 2012 children and adolescents. These reference curves provide the most robust reference values for the assessment and monitoring of bone health in children and adolescents in the literature to date. PMID:21917867

  19. Bone age assessment by dual-energy X-ray absorptiometry in children: an alternative for X-ray?

    PubMed Central

    Heppe, D H M; Taal, H R; Ernst, G D S; Van Den Akker, E L T; Lequin, M M H; Hokken-Koelega, A C S; Geelhoed, J J M; Jaddoe, V W V

    2012-01-01

    Objective The aim of the study was to validate dual-energy X-ray absorptiometry (DXA) as a method to assess bone age in children. Methods Paired dual-energy X-ray absorptiometry (DXA) scans and X-rays of the left hand were performed in 95 children who attended the paediatric endocrinology outpatient clinic of University Hospital Rotterdam, the Netherlands. We compared bone age assessments by DXA scan with those performed by X-ray. Bone age assessment was performed by two blinded observers according to the reference method of Greulich and Pyle. Intra-observer and interobserver reproducibility were investigated using the intraclass correlation coefficient (ICC), and agreement was tested using Bland and Altman plots. Results The intra-observer ICCs for both observers were 0.997 and 0.991 for X-ray and 0.993 and 0.987 for DXA assessments. The interobserver ICC was 0.993 and 0.991 for X-ray and DXA assessments, respectively. The mean difference between bone age assessed by X-ray and DXA was 0.11 years. The limits of agreement ranged from −0.82 to 1.05 years, which means that 95% of all differences between the methods were covered by this range. Conclusions Results of bone age assessment by DXA scan are similar to those obtained by X-ray. The DXA method seems to be an alternative for assessing bone age in a paediatric hospital-based population. PMID:21586503

  20. [A study on observation of bone metabolism in middle-aged and senile female Graves' disease].

    PubMed

    Zhu, L Q; Liu, Y H; Zhou, Y B

    1996-08-01

    Sixty-nine cases of middle aged and senile female Graves' desease (GD) patients suffered from abnormal bone metabolism have been studied. They were divided randomly into group A and B, treated separately with antithyroid drugs (Tapazol and inderal, etc.) in group A, and added with Chinese herbal medicine for tonifying Kidney and promoting blood circulation in group B. Before treatment, patients of both groups showed obvious higher blood calcium (Ca) 24-hour urinary Ca, phosphorus (P) and serum clcitonin (CT) levels than that in normal subjects. These patients' serum Ca, moreover, had a parallel relationship with serum T3 levels (r = 0.6142, P < 0.01) and the serum Ca also a paralleled with serum CT levels (r = 0.5714, P < 0.05). After six months of treatment, the serum Ca, 24-hour urinary Ca, P and blood CT values were all reduced in various degree. The decrease of these bone metabolic parameters were more significant in group B than that in group A. PMID:9387746

  1. Mitochondrial dynamics: Orchestrating the journey to advanced age.

    PubMed

    Biala, Agnieszka K; Dhingra, Rimpy; Kirshenbaum, Lorrie A

    2015-06-01

    Aging is a degenerative process that unfortunately is an inevitable part of life and risk factor for cardiovascular disease including heart failure. Among the several theories purported to explain the effects of age on cardiac dysfunction, the mitochondrion has emerged a central regulator of this process. Hence, it is not surprising that abnormalities in mitochondrial quality control including biogenesis and turnover have such detrimental effects on cardiac function. In fact mitochondria serve as a conduit for biological signals for apoptosis, necrosis and autophagy respectively. The removal of damaged mitochondria by autophagy/mitophagy is essential for mitochondrial quality control and cardiac homeostasis. Defects in mitochondrial dynamism fission/fusion events have been linked to cardiac senescence and heart failure. In this review we discuss the impact of aging on mitochondrial dynamics and senescence on cardiovascular health. This article is part of a Special Issue entitled: CV Aging. PMID:25918048

  2. Quantification of Age-Related Tissue-Level Failure Strains of Rat Femoral Cortical Bones Using an Approach Combining Macrocompressive Test and Microfinite Element Analysis.

    PubMed

    Fan, Ruoxun; Gong, He; Zhang, Rui; Gao, Jiazi; Jia, Zhengbin; Hu, Yanjuan

    2016-04-01

    Bone mechanical properties vary with age; meanwhile, a close relationship exists among bone mechanical properties at different levels. Therefore, conducting multilevel analyses for bone structures with different ages are necessary to elucidate the effects of aging on bone mechanical properties at different levels. In this study, an approach that combined microfinite element (micro-FE) analysis and macrocompressive test was established to simulate the failure of male rat femoral cortical bone. Micro-FE analyses were primarily performed for rat cortical bones with different ages to simulate their failure processes under compressive load. Tissue-level failure strains in tension and compression of these cortical bones were then back-calculated by fitting the experimental stress-strain curves. Thus, tissue-level failure strains of rat femoral cortical bones with different ages were quantified. The tissue-level failure strain exhibited a biphasic behavior with age: in the period of skeletal maturity (1-7 months of age), the failure strain gradually increased; when the rat exceeded 7 months of age, the failure strain sharply decreased. In the period of skeletal maturity, both the macro- and tissue-levels mechanical properties showed a large promotion. In the period of skeletal aging (9-15 months of age), the tissue-level mechanical properties sharply deteriorated; however, the macromechanical properties only slightly deteriorated. The age-related changes in tissue-level failure strain were revealed through the analysis of male rat femoral cortical bones with different ages, which provided a theoretical basis to understand the relationship between rat cortical bone mechanical properties at macro- and tissue-levels and decrease of bone strength with age. PMID:26902102

  3. Inhibition and breaking of advanced glycation end-products (AGEs) with bis-2-aminoimidazole derivatives

    PubMed Central

    Richardson, Mike A.; Furlani, Robert E.; Podell, Brendan K.; Ackart, David F.; Haugen, Jessica D.; Melander, Roberta J.; Melander, Christian; Basaraba, Randall J.

    2015-01-01

    Advanced glycation end-products (AGEs), unregulated modifications to host macromolecules that occur as a result of metabolic dysregulation, play a role in many diabetes related complications, inflammation and aging, and may lead to increased cardiovascular risk. Small molecules that have the ability to inhibit AGE formation, and even break preformed AGEs have enormous therapeutic potential in the treatment of these disease states. We report the screening of a series of 2-aminoimidazloles for anti-AGE activity, and the identification of a bis-2-aminoimidazole lead compound that possesses superior AGE inhibition and breaking activity compared to the known AGE inhibitor aminoguanidine. PMID:26146419

  4. Influence of age on rat bone-marrow mesenchymal stem cells potential

    PubMed Central

    Fafián-Labora, J.; Fernández-Pernas, P.; Fuentes, I.; De Toro, J.; Oreiro, N.; Sangiao-Alvarellos, S.; Mateos, J.; Arufe, M.C.

    2015-01-01

    Mesenchymal stem cells promising role in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age. Six age groups from bone marrow mesenchymal stem cells of Wistar rats were studied (newborn, infant, young, pre-pubertal, pubertal and adult). Quantitative proteomic assay was performance by iTRAQ using an 8-plex iTRAQ labeling and the proteins differentially expressed were grouped in pluripotency, proliferative and metabolism processes. Proliferation makers, CD117 and Ki67 were measure by flow cytometry assay. Real time polymerase chain reaction analysis of pluripotency markers Rex1, Oct4, Sox2 and Nanog were done. Biological differentiation was realized using specific mediums for 14 days to induce osteogenesis, adipogenesis or chondrogenesis and immunostain analysis of differentiated cell resulting were done. Enzimoimmunoassay analysis of several enzymes as L-lactate dehydrogenase and glucose-6-phosphate isomerase were also done to validate iTRAQ data. Taking together these results indicate for the first time that mesenchymal stem cells have significant differences in their proliferative, pluripotency and metabolism profiles and those differences are age depending. PMID:26581954

  5. Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide.

    PubMed

    Fei, Fan; Lee, Keith M; McCarry, Brian E; Bowdish, Dawn M E

    2016-01-01

    Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6-8 wk) and old (18-22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age. PMID:26940652

  6. Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide

    NASA Astrophysics Data System (ADS)

    Fei, Fan; Lee, Keith M.; McCarry, Brian E.; Bowdish, Dawn M. E.

    2016-03-01

    Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6–8 wk) and old (18–22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age.

  7. Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide

    PubMed Central

    Fei, Fan; Lee, Keith M.; McCarry, Brian E.; Bowdish, Dawn M. E.

    2016-01-01

    Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6–8 wk) and old (18–22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age. PMID:26940652

  8. IN VIVO PERFORMANCE OF THE EXPERIMENTAL CHITOSAN BASED BONE SUBSTITUTE--ADVANCED THERAPY MEDICINAL PRODUCT. A STUDY IN SHEEP.

    PubMed

    Bojar, Witold; Kucharska, Martyna; Ciach, Tomasz; Paśnik, Iwona; Korobowicz, Elzbieta; Patkowski, Krzysztof; Gruszecki, Tomasz; Szymanowski, Marek; Rzodkiewicz, Przemysław

    2016-01-01

    When evaluating a novel bone substitute material, advanced in vivo testing is an important step in development and safety affirmation. Sheep seems to be a valuable model for human bone turnover and remodeling activity. The experimental material composed with the stem cells is an advanced therapy medicinal product (acc. to EC Regulation 1394/2007). Our research focuses on histological differences in bone formation (guided bone regeneration--GBR) in sheep maxillas after implantation of the new chitosan/tricalcium phosphate/alginate (CH/TCP/Alg) biomaterial in comparison to the commercially available xenogenic bone graft and a/m enhanced with the stem cells isolated from the adipose tissue. Twelve adult female sheep of BCP synthetic line, weighing 60-70 kg were used for the study. The 11 mm diameter defects in maxilla bone were prepared with a trephine bur under general anesthesia and then filled with the bone substitute materials: CH/TCP/Alg, BioOss Collagen, Geistlich AG (BO), CH/TCP/Alg composed with the stem cells (CH/S) or left just with the blood clot (BC). Inbreeding cycle of the animals terminated at 4 months after surgery. Dissected specimens of the maxilla were evaluated histologically and preliminary under microtomography. Histological evaluation showed early new bone formation observed around the experimental biomaterial and commercially available BO. There were no features of purulent inflammation and necrosis, or granulomatous inflammation. Microscopic examination after 4 months following the surgery revealed trabecular bone formation around chitosan based bone graft and xenogenic material with no significant inflammatory response. Different results--no bone recreation were observed for the negative control (BC). In conclusion, the tested materials (CH/TCP/Alg and BO) showed a high degree of biocompatibility and some osteoconductivity in comparison with the control group. Although the handiness, granules size and setting time of CHffCP/Alg may be refined

  9. Advanced Paternal Age at Birth: Phenotypic and Etiologic Associations with Eating Pathology in Offspring

    PubMed Central

    Racine, Sarah E.; Culbert, Kristen M.; Burt, S. Alexandra; Klump, Kelly L.

    2013-01-01

    Background Advanced paternal age at birth has been linked to several psychiatric disorders in offspring (e.g., schizophrenia), and genetic mechanisms are thought to underlie these associations. This study is the first to investigate whether advanced paternal age at birth is associated with eating disorder risk using a twin study design capable of examining both phenotypic and genetic associations. Methods In a large, population-based sample of female twins ages 8–17 years in mid-puberty or beyond (N = 1,722), we investigated whether advanced paternal age was positively associated with disordered eating symptoms and an eating disorder history (i.e., anorexia nervosa, bulimia nervosa, or binge eating disorder) in offspring. Biometric twin models examined whether genetic and/or environmental factors underlie paternal age effects for disordered eating symptoms. Results Advanced paternal age was positively associated with disordered eating symptoms and an eating disorder history, where the highest level of pathology was observed in offspring born to fathers ≥ 40 years old. Results were not accounted for by maternal age at birth, body mass index, socioeconomic status, fertility treatment, or parental psychiatric history. Twin models indicated decreased genetic, and increased environmental, effects on disordered eating with advanced paternal age. Conclusions Advanced paternal age increased risk for the full spectrum of eating pathology, independent of several important covariates. However, contrary to leading hypotheses, environmental rather than genetic factors accounted for paternal age-disordered eating associations. These data highlight the need to explore novel (potentially environmental) mechanisms underlying the effects of advanced paternal age on offspring eating disorder risk. PMID:23795717

  10. Morphological study of the human hyoid bone with three-dimensional CT images -Gender difference and age-related changes.

    PubMed

    Ito, Kyoichi; Ando, Satoshi; Akiba, Norihiko; Watanabe, Yuichi; Okuyama, Yasuo; Moriguchi, Hisamoto; Yoshikawa, Kohki; Takahashi, Tsuneo; Shimada, Morio

    2012-01-01

    The human hyoid bone supports the base of the tongue and is involved in breathing, chewing, and swallowing as well as in the muscle movements associated with articulation. Accordingly it plays an important bone for a human to live. It is a very interesting organ also in multiple special area, including anatomy, mastication, swallowing, articulation, and also forensic medicine. In the morphological study of the human hyoid bone, there is a comparative anthropological research early in 1900, whereas the metrological research has been little reported later. We first used MDCT, and recorded each organic hyoid locus with a three-dimensional image for three-dimensional morphometry of gender differences, age-related changes, and the morphologic characters of the hyoid bone, and compared them with the results of our predecessors. By measuring the volume of the human hyoid bone, we identified gender difference at high rates, and estimated a certain level of ages based on the ossification at the junction area of the hyoid body and greater horns observed. Our results can be applied in the forensic medicine. By examining 600 cases, atypical horseshoes-shapes were found and the existence of the hyoid bone protrusion was demonstrated at high rates. PMID:23429053

  11. Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-β expression and secretion.

    PubMed

    Notsu, Masakazu; Yamaguchi, Toru; Okazaki, Kyoko; Tanaka, Ken-ichiro; Ogawa, Noriko; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2014-07-01

    In diabetic patients, advanced glycation end products (AGEs) cause bone fragility because of deterioration of bone quality. We previously showed that AGEs suppressed the mineralization of mouse stromal ST2 cells. TGF-β is abundant in bone, and enhancement of its signal causes bone quality deterioration. However, whether TGF-β signaling is involved in the AGE-induced suppression of mineralization during the osteoblast lineage remains unknown. We therefore examined the roles of TGF-β in the AGE-induced suppression of mineralization of ST2 cells and human mesenchymal stem cells. AGE3 significantly (P < .001) inhibited mineralization in both cell types, whereas transfection with small interfering RNA for the receptor for AGEs (RAGEs) significantly (P < .05) recovered this process in ST2 cells. AGE3 increased (P < .001) the expression of TGF-β mRNA and protein, which was partially antagonized by transfection with RAGE small interfering RNA. Treatment with a TGF-β type I receptor kinase inhibitor, SD208, recovered AGE3-induced decreases in osterix (P < .001) and osteocalcin (P < .05) and antagonized the AGE3-induced increase in Runx2 mRNA expression in ST2 cells (P < .001). Moreover, SD208 completely and dose dependently rescued AGE3-induced suppression of mineralization in both cell types. In contrast, SD208 intensified AGE3-induced suppression of cell proliferation as well as AGE3-induced apoptosis in proliferating ST2 cells. These findings indicate that, after cells become confluent, AGE3 partially inhibits the differentiation and mineralization of osteoblastic cells by binding to RAGE and increasing TGF-β expression and secretion. They also suggest that TGF-β adversely affects bone quality not only in primary osteoporosis but also in diabetes-related bone disorder. PMID:24758301

  12. Recent female mouse models displaying advanced reproductive aging.

    PubMed

    Danilovich, Natalia; Ram Sairam, M

    2006-02-01

    Reproductive senescence occurs in all female mammals with resultant changes in numerous body functional systems and several important features may be species-specific. Those features that appear to parallel human menopause and aging include general similarity of hormone profiles across the menopausal transition, progression to cycle termination through irregular cycles, declining fertility with age, disturbances in thermogenesis, age-related gains in body weight, fat distribution and disposition towards metabolic syndrome. Structural and hormonal changes in the brain and ovary play a critical role in determining the onset of reproductive senescence. The short life span of rodents such as mice (compared to humans) and the ability to generate specific and timed gene deletions, provide powerful experimental paradigms to understand the molecular and functional changes that precede and follow the loss of reproductive capacity. In theory, any manipulation that compromises ovarian function either partly or totally would impact reproductive events at various levels followed by other dysfunctions. In this article, we provide an overview of three mouse models for the study of female reproductive aging. They are derived from different strategies and their age related phenotypes have been characterized to varying degrees. The follitropin receptor knockout (FORKO) mouse, in its null and haploinsufficient state as well as the dioxin/aryl hydrocarbon receptor (AhR) knockout mouse, serve as two examples of single gene deletions. A third model, using administration of a chemical toxicant such as 4-vinylcyclohexene diepoxide (VCD) in the adult state, produces ovarian deficiencies accompanied by aging changes. These will serve as useful alternatives to previously used radical ovariectomy in young adults. It is anticipated that these new models and more that will be forthcoming will extend opportunities to understand reproductive aging and resolve controversies that abound on issues

  13. Bone Quality in Diabetes

    PubMed Central

    Saito, Mitsuru; Marumo, Keishi

    2013-01-01

    Diabetes is associated with increased risk of fracture, although type 2 diabetes is characterized by normal bone mineral density (BMD). The fracture risk of type 1 diabetes increases beyond an explained by a decrease of BMD. Thus, diabetes may be associated with a reduction of bone strength that is not reflected in the measurement of BMD. Based on the present definition, both bone density and quality, which encompass the structural and material properties of bone, are important factors in the determination of bone strength. Diabetes reduces bone quality rather than BMD. Collagen cross-linking plays an important role in bone strength. Collagen cross-links can be divided into lysyl hydroxylase and lysyl oxidase-mediated enzymatic immature divalent cross-links, mature trivalent cross-links, and glycation- or oxidation-induced non-enzymatic cross-links (Advanced Glycation End-products: AGEs) such as pentosidine. These types of cross-links differ in the mechanism of formation and in function. Not only hyperglycemia, but also oxidative stress induces the reduction in enzymatic beneficial cross-links and the accumulation of disadvantageous AGEs in bone. In this review, we describe the mechanism of low bone quality in diabetes. PMID:23785354

  14. Effects of age and dietary soybean oil level on eggshell quality, bone strength and blood biochemistry in laying hens.

    PubMed

    Jiang, S; Cui, L Y; Hou, J F; Shi, C; Ke, X; Yang, L C; Ma, X P

    2014-01-01

    The objective of the study was to investigate the differences in eggshell quality, bone quality and serum bone biochemistry markers associated with changes in age and dietary soybean oil levels in laying hens. A total of 54, 19-week-old Hy-Line Brown laying hens were housed in 18 battery cages (3 birds/cage) and randomly divided into three diet treatments for 90 d: control-fat (CF, 1.9% soybean oil), moderate-fat (MF, 7% soybean oil) and high-fat (HF, 10% soybean oil). The hens' body weights (BW), egg production, egg weights, eggshell thickness and femoral diameter were higher at d 90 than at d 60 or d 30. Meanwhile, feed intake, relative bone weights, all bone strength parameters and serum Ca were lower at d 90 or 60 than at d 30. Compared to the CF hens, the feed intake, BW, abdominal fat pad weights and serum alkaline phosphatase activity were elevated in MF or HF hens. The eggshell thickness, relative femoral and tibial weight, femoral stiffness, femoral modulus, tibial mixed force and serum calcium and phosphorus levels were lower in MF or HF hens than CF hens. These findings suggest that bone loss in caged hens starts from an early stage of the laying period, and dietary oil (particularly with diets over 10% soybean oil) has harmful effects on eggshell quality, bone strength and bone mineralisation from an early stage of the laying period. PMID:25109942

  15. Study of Different Involutive Changes in Bone Mineral Density Measured in Ward's Triangle and Trabecular Volume Measured in Iliac Crest in Relation to Age

    PubMed Central

    Castillo, RF; Gallegos, RF

    2015-01-01

    ABSTRACT Background: The ageing process causes changes in the bone structure, in bone mineral density, and musculoskeletal disorders. Aims: The purpose of this study is to evaluate and compare involutive changes in bone structure that occur in relation to age in men and women through the study of bone mineral density at the Ward's triangle and trabecular volume. Subjects and Methods: In this study, we analysed bone mineral density at Ward's triangle in 70 people (38 men and 32 women) and did a histomorphometric study of trabecular volume at the right iliac crest in 66 samples (42 males and 24 females) obtained from autopsies of court cases, aged between 13 and 83 years. Results: The results show significant correlations between measurements of bone mineral density, trabecular volume values and anthropometric measures of age, gender and body mass index. Conclusions: This study shows involutional changes that occur in the bone mineral density and Ward's triangle in the bone structure during the process of ageing. In addition, both weight and height have a great influence on bone mineral density and changes in bone that occur; and body mass index is a very important determinant of bone mineral density. PMID:26360671

  16. The effect of age, sex hormones, and bone turnover markers on calcaneal quantitative ultrasonometry in healthy German men.

    PubMed

    Kyvernitakis, Ioannis; Saeger, Ulf; Ziller, Volker; Bauer, Thomas; Seker-Pektas, Berna; Hadji, Peyman

    2013-01-01

    The aim of this cross-sectional study was to determine the age-dependent variations of calcaneal quantitative ultrasonometry (QUS) and the association with sex hormones and biochemical bone turnover markers in a large sample of unselected healthy German men. Bone measurements are expected to behave differently among men and women. The speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcaneus were measured in 506 German men aged 20-79 yr (mean age: 45.7 yr). Additionally, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) as well as N-terminal propeptide of human procollagen type I (PINP), C-terminal telopeptide of type I collagen (ICTP), osteocalcin, bone-specific alkaline phosphatase, and CrossLaps were measured with standardized essays and correlated with the QUS results. The QUS results comprised an overall change of 12.4%, 3.2%, and 23.2% for BUA, SOS, and SI, respectively, between the 20-29 and 70-79 yr age groups (p ≤ 0.001). The annual rate of the age-related differences was 0.33% (standard deviation [SD]: 0.31), 0.06% (SD: 0.08), and 0.53% (SD: 0.56) for BUA, SOS, and SI, respectively. Testosterone and DHEA-S were significantly associated with QUS parameters and increasing age, whereas SHBG showed an age-related increase and was inversely related with QUS values (p < 0.05). Bone turnover markers present lower values gradually, and we found a significant correlation between carboxy-terminal collagen crosslinks (CTX), osteocalcin (OC), bone alkaline phosphatase (BAP), and QUS variables (p < 0.05). PMID:23582469

  17. Age estimation of immature human skeletal remains from the diaphyseal length of the long bones in the postnatal period.

    PubMed

    Cardoso, Hugo F V; Abrantes, Joana; Humphrey, Louise T

    2014-09-01

    Age at death in immature human skeletal remains has been estimated from the diaphyseal length of the long bones, but few studies have actually been designed specifically for the purpose of age estimation and those which have, show important caveats. This study uses regression and classical calibration to model the relationship between age and diaphyseal length of the six long bones, in a sample of 184 known sex and age individuals (72 females and 112 males), younger than 13 years of age, selected from Portuguese and English skeletal collections. Age estimation models based on classical calibration were obtained for each of the six long bones, and separately for each sex and for the sexes combined, and also for the entire sample and when it is subdivided into two subsamples at the age of 2 years. Comparisons between inverse and classical calibration show there is a systematic bias in age estimations obtained from inverse calibration. In the classical calibration models, the length of the femur provides the most accurate estimates of age. Age estimates are more accurate for the male subsample and for individuals under the age of 2 years. These results and a test of previously published methods caution against inverse calibration as a technique for developing age estimation methods even from the immature skeleton. Age estimation methods developed using cemetery collections of identified human skeletons should not be uncritically applied to present-day populations from the same region since many populations have experienced dramatic secular trends in growth and adult height over the last century. PMID:24126574

  18. Human mortality at very advanced age might be constant.

    PubMed

    Klemera, P; Doubal, S

    1997-11-01

    An attempt was made to identify the course of the mortality rate at the upper tail of human age. The only known data suitable for this purpose were published by Riggs and Millecchia (J.E. Riggs, R.J. Millecchia, Mech. Ageing Dev. 62 (1992) 191-199) and our analysis follows up their results. By means of mathematical elaboration it was proved that these data imply a constant mortality rate (approx. 25% per year) at ages above 113 years for men and above 116 years for women. Indirect arguments supporting the validity of the source data are discussed. Nevertheless, even if the source data are mistaken, we proved they cannot be the product of purely random errors and our results may contribute to the elucidation of the origin of those systematic errors. PMID:9379712

  19. Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

    PubMed Central

    Miyahara, Koji; Nouso, Kazuhiro; Yamamoto, Kazuhide

    2014-01-01

    The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conventional characteristics of patients, there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of sorafenib. Risk and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet exists. In addition, effectiveness of the expanded application of sorafenib is still controversial, although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage HCC. Recently, over 50 relevant drugs have been developed and are currently under investigation. The efficacy of some of these drugs has been extensively examined, but none have demonstrated any superiority over sorafenib, so far. However, there are several drugs that have shown efficacy for treatment after sorafenib failure, and these are proceeding to further studies. To address these issues and questions, we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib. PMID:24764653

  20. Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype?

    PubMed Central

    Nicklett, Emily J.; Ferrucci, Luigi

    2010-01-01

    Background. Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. Methods. We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids. Results. Humans are exposed to AGEs produced in the body, especially in individuals with abnormal glucose metabolism, and AGEs ingested in foods. AGEs cause widespread damage to tissues through upregulation of inflammation and cross-linking of collagen and other proteins. AGEs have been shown to adversely affect virtually all cells, tissues, and organ systems. Recent epidemiological studies demonstrate that elevated circulating AGEs are associated with increased risk of developing many chronic diseases that disproportionally affect older individuals. Conclusions. Based on these data, we propose that accumulation of AGEs accelerate the multisystem functional decline that occurs with aging, and therefore contribute to the aging phenotype. Exposure to AGEs can be reduced by restriction of dietary intake of AGEs and drug treatment with AGE inhibitors and AGE breakers. Modification of intake and circulating levels of AGEs may be a possible strategy to promote health in old age, especially because most Western foods are processed at high temperature and are rich in AGEs. PMID:20478906

  1. The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain

    PubMed Central

    Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2010-01-01

    As humans age there is a decline in most sensory systems including vision, hearing, taste, smell, and tactile acuity. In contrast, the frequency and severity of musculoskeletal pain generally increases with age. To determine whether the density of sensory nerve fibers that transduce skeletal pain changes with age, calcitonin gene related peptide (CGRP) and neurofilament 200 kDa (NF200) sensory nerve fibers that innervate the femur were examined in the femurs of young (4 month old), middle-aged (13 month) and old (36 month) male F344/BNF1 rats. Whereas the bone quality showed a significant age-related decline, the density of CGRP+ and NF200+ nerve fibers that innervate the bone remained remarkably unchanged as well as the severity of acute skeletal fracture pain. Thus, while bone mass, quality and strength undergo a significant decline with age, the density of sensory nerve fibers that transduce noxious stimuli remain largely intact. These data may in part explain why musculoskeletal pain increases with age. PMID:20947214

  2. Recommendations for managing cutaneous disorders associated with advancing age

    PubMed Central

    Humbert, Philippe; Dréno, Brigitte; Krutmann, Jean; Luger, Thomas Anton; Triller, Raoul; Meaume, Sylvie; Seité, Sophie

    2016-01-01

    The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach. PMID:26929610

  3. Recommendations for managing cutaneous disorders associated with advancing age.

    PubMed

    Humbert, Philippe; Dréno, Brigitte; Krutmann, Jean; Luger, Thomas Anton; Triller, Raoul; Meaume, Sylvie; Seité, Sophie

    2016-01-01

    The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach. PMID:26929610

  4. Transportation and Aging: A Research Agenda for Advancing Safe Mobility

    ERIC Educational Resources Information Center

    Dickerson, Anne E.; Molnar, Lisa J.; Eby, David W.; Adler, Geri; Bedard, Michel; Berg-Weger, Marla; Classen, Sherrilene; Foley, Daniel; Horowitz, Amy; Kerschner, Helen; Page, Oliver; Silverstein, Nina M.; Staplin, Loren; Trujillo, Leonard

    2007-01-01

    Purpose: We review what we currently know about older driver safety and mobility, and we highlight important research needs in a number of key areas that hold promise for achieving the safety and mobility goals for the aging baby boomers and future generations of older drivers. Design and Methods: Through the use of a framework for transportation…

  5. Tracing the pathway of compositional changes in bone mineral with age: Preliminary study of bioapatite aging in hypermineralized dolphin’s bulla

    PubMed Central

    Li, Zhen; Pasteris, Jill D.

    2014-01-01

    Background Studies of mineral compositional effects during bone aging are complicated by the presence of collagen. Methods Hypermineralized bullae of Atlantic bottlenose dolphins of < 3 months, 2.5 years, and 20 years underwent micrometer-scale point analysis by Raman spectroscopy and electron microprobe in addition to bulk analysis for carbon. Results Bulla central areas have a mineral content of ~96 wt.% and 9–10 wt.% carbonate in their bioapatite, which is ~2 wt.% more than edge areas. Ca/P atomic ratios (~1.8) and concentrations of Mg, S, and other minor/trace elements are almost constant in central areas over time. Maturity brings greater over-all homogeneity in mineral content, stoichiometry, and morphology throughout central and edge areas of the bullae. During aging, edge areas become less porous, whereas the concentration of organics in the edge is reduced. Enhancement of coupled substitutions of CO32− for PO43− and Na for Ca during aging increases carbonate content up to ~10 wt.% in the adult bulla. Conclusions 1) Changes in physical properties during aging did not occur simultaneously with changes in chemical properties of the bone mineral. 2) Compositional changes in bone mineral were minor during the neonatal to sub-adult stage, but significant during later maturity. 3) Na and CO3 concentrations covary in a 1:1 molar proportion during aging. 4) The mineral’s crystallinity did not decrease as CO3 concentration increased during aging. General Significance Hypermineralized dolphin’s bulla, due to extreme depletion in collagen, is an ideal material for investigating mineralogical changes in bioapatite during bone aging. PMID:24650888

  6. Bone Health and Osteoporosis: A Guide for Asian Women Aged 50 and Older

    MedlinePlus

    ... Bone Health for Lupus Patients Bone Health and Anorexia Nervosa Partner Resources Health Problems in Asian American/ ... medications such as corticosteroids and anticonvulsants history of anorexia nervosa. What Is Osteoporosis? Osteoporosis is a disease ...

  7. Perceptual restoration of degraded speech is preserved with advancing age.

    PubMed

    Saija, Jefta D; Akyürek, Elkan G; Andringa, Tjeerd C; Başkent, Deniz

    2014-02-01

    Cognitive skills, such as processing speed, memory functioning, and the ability to divide attention, are known to diminish with aging. The present study shows that, despite these changes, older adults can successfully compensate for degradations in speech perception. Critically, the older participants of this study were not pre-selected for high performance on cognitive tasks, but only screened for normal hearing. We measured the compensation for speech degradation using phonemic restoration, where intelligibility of degraded speech is enhanced using top-down repair mechanisms. Linguistic knowledge, Gestalt principles of perception, and expectations based on situational and linguistic context are used to effectively fill in the inaudible masked speech portions. A positive compensation effect was previously observed only with young normal hearing people, but not with older hearing-impaired populations, leaving the question whether the lack of compensation was due to aging or due to age-related hearing problems. Older participants in the present study showed poorer intelligibility of degraded speech than the younger group, as expected from previous reports of aging effects. However, in conditions that induce top-down restoration, a robust compensation was observed. Speech perception by the older group was enhanced, and the enhancement effect was similar to that observed with the younger group. This effect was even stronger with slowed-down speech, which gives more time for cognitive processing. Based on previous research, the likely explanations for these observations are that older adults can overcome age-related cognitive deterioration by relying on linguistic skills and vocabulary that they have accumulated over their lifetime. Alternatively, or simultaneously, they may use different cerebral activation patterns or exert more mental effort. This positive finding on top-down restoration skills by the older individuals suggests that new cognitive training methods

  8. Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing

    PubMed Central

    Javaheri, B.; Carriero, A.; Staines, K.A.; Chang, Y.-M.; Houston, D.A.; Oldknow, K.J.; Millan, J.L.; Kazeruni, Bassir N.; Salmon, P.; Shefelbine, S.; Farquharson, C.; Pitsillides, A.A.

    2015-01-01

    PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay

  9. Relationship of lead in drinking water to bone lead levels twenty years later in Boston men: the Normative Aging Study.

    PubMed

    Potula, V; Serrano, J; Sparrow, D; Hu, H

    1999-05-01

    Tap water in a city like Boston, which has old houses containing lead plumbing, is known to be a significant source of potential lead exposure. Bone lead levels integrate exposure over many years, and in vivo bone lead measurements have recently become possible with the advent of K x-ray fluorescence instruments. Thus we examined the relationship between first morning tap-water lead levels measured in homes in the 1970s and levels of lead in bone measured in the 1990s among middle-aged to elderly men who lived in those homes. We studied 129 participants in the Normative Aging Study who had lead measured in their homes' tap water in 1976 and 1977 by graphite furnace-atomic absorption spectrophotometry. From 1991 to 1995, the same subjects had blood lead levels measured by graphite furnace-atomic absorption spectroscopy and tibia and patella bone lead levels measured by K x-ray fluorescence. We ran multivariate linear regression models predicting bone lead levels that adjusted for factors which had previously been linked with this outcome in the Normative Aging Study (age, pack-years of smoking, and educational level). Among subjects who lived in houses with > or = 50 micrograms lead/liter of first morning tap water representing water that had been standing overnight in the plumbing in 1976 and 1977, those who reported medium or high levels of tap-water ingestion (> or = 1 glass/day) had progressively higher patella lead levels than did those with low levels of ingestion (< 1 glass/day). No such relationship was found among subjects who lived in houses with < 50 micrograms lead/liter of first morning tap water in 1976 and 1977. We conclude that ingestion of lead-contaminated tap water is an important predictor of elevated bone lead levels later in life. PMID:10337604

  10. Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales.

    PubMed

    Zimmermann, Elizabeth A; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D; Tang, Simon Y; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager, Joel W; Ritchie, Robert O

    2011-08-30

    The structure of human cortical bone evolves over multiple length scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at near-millimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone's toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural scales typically below a micrometer and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple length scales. Using in situ small-angle X-ray scattering and wide-angle X-ray diffraction to characterize submicrometer structural changes and synchrotron X-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micrometer scales, we show how these age-related structural changes at differing size scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased nonenzymatic collagen cross-linking, which suppresses plasticity at nanoscale dimensions, and to an increased osteonal density, which limits the potency of crack-bridging mechanisms at micrometer scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by "plastic" deformation at higher structural levels, which occurs by the process of microcracking. PMID:21873221

  11. Association of Renal Function and Menopausal Status with Bone Mineral Density in Middle-aged Women

    PubMed Central

    Sheng, Yueh-Hsuan; Chen, Jen-Hau; Chiou, Jeng-Min; Tsai, Keh-Sung; Lee, Yue-Yuan; Tsao, Chwen-Keng; Chen, Yen-Ching

    2015-01-01

    The association between mild renal dysfunction and bone mineral density (BMD) has not been fully explored. It is also unclear how menopausal status and the use of Chinese herb affect this association. This is a cross-sectional study that included a total of 1,419 women aged 40 to 55 years old who were recruited from the MJ Health Management Institution in Taiwan between 2009 and 2010. Spinal BMD was assessed by dual-energy X-ray absorptiometry. Renal function was assessed using estimated glomerular filtration rate (eGFR) and creatinine clearance rate (CCr). The multivariable logistic regression and general linear models were employed to assess the association between renal function and BMD. Stratification analyses were performed by menopausal status and use of Chinese herbs. Low CCr levels were significantly associated with low BMD [adjusted odds ratio (AOR) = 1.48, 95% confidence interval (CI) = 1.15–1.90]. This association was observed in premenopausal women (AOR = 1.43, 95% CI = 1.07–1.92) and in women not taking Chinese herbs (AOR = 1.48, 95% CI = 1.14–1.94). CCr is a better predictor for low BMD in middle-aged women. Menopausal status and the use of Chinese herbs also affected this association. PMID:26459876

  12. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice.

    PubMed

    Ohshima, T; Schiffmann, R; Murray, G J; Kopp, J; Quirk, J M; Stahl, S; Chan, C C; Zerfas, P; Tao-Cheng, J H; Ward, J M; Brady, R O; Kulkarni, A B

    1999-05-25

    Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha-galactosidase A (alpha-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated alpha-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of alpha-Gal A -/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of alpha-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease. PMID:10339603

  13. Middle-Aged Independent-Living African Americans' Selections for Advance Directives: A Case Study

    ERIC Educational Resources Information Center

    McDaniel, Brenda J.

    2013-01-01

    The purpose of this collective embedded qualitative case study was to examine the perspectives of three middle-aged independent-living African Americans who had participated in the process of advance care planning (ACP) and completed at least two advance directives (ADs), a Durable Power of Attorney for Health Care (DPAHC) and a Living Will (LW).…

  14. Electrophysiological Advances on Multiple Object Processing in Aging

    PubMed Central

    Mazza, Veronica; Brignani, Debora

    2016-01-01

    EEG research conducted in the past 5 years on multiple object processing has begun to define how the aging brain tracks the numerosity of the objects presented in the visual field for different goals. We review the recent EEG findings in healthy older individuals (age range: 65–75 years approximately) on perceptual, attentional and memory mechanisms-reflected in the N1, N2pc and contralateral delayed activity (CDA) components of the EEG, respectively-during the execution of a variety of cognitive tasks requiring simultaneous processing of multiple elements. The findings point to multiple loci of neural changes in multi-object analysis, and suggest the involvement of early perceptual mechanisms, attentive individuation and working memory (WM) operations in the neural and cognitive modification due to aging. However, the findings do not simply reflect early impairments with a cascade effect over subsequent stages of stimulus processing, but in fact highlight interesting dissociations between the effects occurring at the various stages of stimulus processing. Finally, the results on older adults indicate the occurrence of neural overactivation in association to good levels of performance in easy perceptual contexts, thus providing some hints on the existence of compensatory phenomena that are associated with the functioning of early perceptual mechanisms. PMID:26973520

  15. Side effects of bone-targeted therapies in advanced breast cancer.

    PubMed

    Domschke, Christoph; Schuetz, Florian

    2014-10-01

    In up to 75% of cases, advanced breast cancer patients eventually develop bone metastases with often debilitating skeletal-related events (SREs). Osteoclast inhibitors are commonly used as therapeutic mainstay with clinical studies showing superiority of denosumab over bisphosphonates (e.g., zoledronate) for the prevention of SREs. The present review discusses the adverse event profile of these agents, and addresses the prevention and management of untoward side effects. Adverse events associated with osteoclast inhibitors comprise osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab, particularly in severe renal dysfunction. During therapy, the appropriate prevention of these adverse events includes close attention to dental health, avoidance of invasive dental procedures, supplementation with calcium and vitamin D unless patients are hypercalcemic, and regular monitoring of relevant serum values. Relating to the risk of nephrotoxicity, bisphosphonates but not denosumab have been incriminated. Therefore, serum creatinine levels should be checked prior to each dose of zoledronate, and in severe renal dysfunction (creatinine clearance < 30 ml/min) zoledronate is contraindicated anyway. Acute-phase reactions are particularly linked to bisphosphonates. Consequently, if these adverse events predominate, switching to denosumab is recommended. PMID:25759613

  16. Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men

    PubMed Central

    Beukhof, Carolien M.; Medici, Marco; van den Beld, Annewieke W.; Hollenbach, Birgit; Hoeg, Antonia; Visser, W. Edward; de Herder, Wouter W.; Visser, Theo J.; Schomburg, Lutz; Peeters, Robin P.

    2016-01-01

    Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75–80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population. PMID:27055238

  17. Effects of boric acid supplementation on bone histomorphometry, metabolism, and biomechanical properties in aged female F-344 rats.

    PubMed

    Gallardo-Williams, Maria T; Maronpot, Robert R; Turner, Charles H; Johnson, Christopher S; Harris, Martha W; Jayo, Manuel J; Chapin, Robert E

    2003-01-01

    Postmenopausal women may benefit from dietary interventions in order to increase bone strength and prevent fractures. Dietary boron (B) may be beneficial for optimal calcium metabolism and, as a consequence, optimal bone metabolism. The present study evaluated the effects of boron, in the form of boric acid, with or without 17beta-estradiol (E2) supplementation (via subcutaneous implant), in ovariectomized (OVX) aged 13- mo-old F-344 rats. Boric acid was administered by gavage at a subtoxic dose (8.7 mg B/kg/d) for 40 d. Results indicate that serum level of minerals as well as osteocalcin (a marker of bone resorption) are dependent to a greater extent on the hormonal status of the animals than on boron supplementation. Boron treatment increased the E2-induced elevation of urinary calcium and magnesium. Bone mineral density (BMD) of the L5 vertebra and proximal femur was highest in the E2-treated groups; no increase in BMD was conferred by boron treatment. By histomorphometry of the proximal tibial metaphysis, osteoblastic, osteoid, and eroded surfaces were significantly suppressed by E2 treatment, but not by boron treatment. In biomechanical testing of femur and vertebra, neither E2 nor boron treatment significantly increased bone strength. At the levels given, boron alone provided no protection against OVX-induced osteopenia. In addition, combination therapy (B + E2) provided no additional benefits over those of 17beta-estradiol treatment alone in this aged rat model. PMID:12835499

  18. Age-Related Macular Degeneration: Advances in Management and Diagnosis.

    PubMed

    Yonekawa, Yoshihiro; Miller, Joan W; Kim, Ivana K

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  19. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  20. Weight regulation and bone mass: a comparison between professional jockeys, elite amateur boxers, and age, gender and BMI matched controls.

    PubMed

    Dolan, Eimear; Crabtree, Nicola; McGoldrick, Adrian; Ashley, David T; McCaffrey, Noel; Warrington, Giles D

    2012-03-01

    The aim of this study was to compare bone mass between two groups of jockeys (flat: n = 14; national hunt: n = 16); boxers (n = 14) and age, gender and BMI matched controls (n = 14). All subjects underwent dual energy X-ray absorptiometry (DXA) scanning for assessment of bone mass, with measurements made of the total body, vertebra L2-4 and femoral neck. Body composition and the relative contribution of fat and lean mass were extrapolated from the results. Data were analysed in accordance with differences in body composition, in particular, height, lean mass, fat mass and age. Both jockey groups were shown to display lower bone mass than either the boxers or control group at a number of sites including total body bone mineral density (BMD) (1.019 ± 0.06 and 1.17 ± 1.05 vs. 1.26 ± 0.01 and 1.26 ± 0.06 g cm(-2) for flat, national hunt, boxer and control, respectively), total body bone mineral content (BMC) less head, L2-4 BMD and femoral neck BMD and BMC (p < 0.05). Regression analysis revealed that lean mass and height were the primary predictors of total body BMC, although additional group-specific influences were present which reduced bone mass in the flat jockey group and enhanced it in the boxers (R (2) = 0.814). Reduced bone mass in jockeys may be a consequence of reduced energy availability in response to chronic weight restriction and could have particular implications for these athletes in light of the high risk nature of the sport. In contrast, the high intensity, high impact training associated with boxing may have conveyed an osteogenic stimulus on these athletes. PMID:21773703

  1. Characteristics of first-time fathers of advanced age: a Norwegian population-based study

    PubMed Central

    2013-01-01

    Background The modern phenomenon of delayed parenthood applies not only to women but also to men, but less is known about what characterises men who are expecting their first child at an advanced age. This study investigates the sociodemographic characteristics, health behaviour, health problems, social relationships and timing of pregnancy in older first-time fathers. Methods A cross-sectional study was conducted of 14 832 men who were expecting their first child, based on data from the Norwegian Mother and Child Cohort Study (MoBa) carried out by the Norwegian Institute of Public Health. Data were collected in 2005–2008 by means of a questionnaire in gestational week 17–18 of their partner’s pregnancy, and from the Norwegian Medical Birth Register. The distribution of background variables was investigated across the age span of 25 years and above. Men of advanced age (35–39 years) and very advanced age (40 years or more) were compared with men aged 25–34 years by means of bivariate and multivariate logistic regression analyses. Results The following factors were found to be associated with having the first child at an advanced or very advanced age: being unmarried or non-cohabitant, negative health behaviour (overweight, obesity, smoking, frequent alcohol intake), physical and mental health problems (lower back pain, cardiovascular diseases, high blood pressure, sleeping problems, previous depressive symptoms), few social contacts and dissatisfaction with partner relationship. There were mixed associations for socioeconomic status: several proxy measures of high socioeconomic status (e.g. income >65 000 €, self-employment) were associated with having the first child at an advanced or very advanced age, as were several other proxy measures of low socioeconomic status (e.g. unemployment, low level of education, immigrant background).The odds of the child being conceived after in vitro fertilisation were threefold in men aged 34–39 and fourfold from 40

  2. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease.

    PubMed

    Claassen, Daniel O; Dobolyi, David G; Isaacs, David A; Roman, Olivia C; Herb, Joshua; Wylie, Scott A; Neimat, Joseph S; Donahue, Manus J; Hedera, Peter; Zald, David H; Landman, Bennett A; Bowman, Aaron B; Dawant, Benoit M; Rane, Swati

    2016-05-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  3. Advanced glycation end-products: a common pathway in diabetes and age-related erectile dysfunction.

    PubMed

    Neves, D

    2013-08-01

    Reactive derivatives of non-enzymatic glucose-protein condensation reactions integrate a heterogeneous group of irreversible adducts called advanced glycation end-products (AGEs). Numerous studies have investigated the role of the AGEs in cardiovascular system; however, its contribution to erectile dysfunction (ED) that is an early manifestation of cardiovascular disease has been less intensively investigated. This review summarizes the most recent advances concerning AGEs effects in the cavernous tissue of the penis and in ED onset, particularly on diabetes and aging, conditions that not only favor AGEs formation, but also increase risk of developing ED. The specific contribution of AGE on intra- and extracellular deposition of insoluble complexes, interference in activity of endothelial nitric oxide (NO) synthase, NO bioavailability, endothelial-dependent vasodilatation, as well as molecular pathways activated by receptor of AGEs are presented. Finally, the interventional actions that prevent AGEs formation, accumulation or activity in the cavernous tissue and that include nutritional pattern modulation, nutraceuticals, exercise, therapeutic strategies (statins, anti-diabetics, inhibitors of phosphodiesterase-5, anti-hypertensive drugs) and inhibitors of AGEs formation and crosslink breakers, are discussed. From this review, we conclude that despite the experiments conducted in animal models pointing to the AGE/RAGE axis as a potential interventional target with respect to ED associated with diabetes and aging, the clinical data have been very disappointing and, until now, did not provide evidence of benefits of treatments directed to AGE inactivation. PMID:23822116

  4. Comparison of DXA Scans and Conventional X-rays for Spine Morphometry and Bone Age Determination in Children.

    PubMed

    Hoyer-Kuhn, Heike; Knoop, Kai; Semler, Oliver; Kuhr, Kathrin; Hellmich, Martin; Schoenau, Eckhard; Koerber, Friederike

    2016-01-01

    Conventional lateral spine and hand radiographs are the standard tools to evaluate vertebral morphometry and bone age in children. Beside bone mineral density analyses, dual-energy X-ray absorptiometry (DXA) measurements with lower radiation exposure provide high-resolution scans which are not approved for diagnostic purposes. Data about the comparability of conventional radiographs and DXA in children are missing yet. The purpose of the trial was to evaluate whether conventional hand and spine radiographs can be replaced by DXA scans to diminish radiation exposure. Thirty-eight children with osteogenesis imperfecta or secondary osteoporosis or short stature (male, n=20; age, 5.0-17.0 yr) were included and assessed once by additional DXA (GE iDXA) of the spine or the left hand. Intraclass correlation coefficients (ICCs) were used to express agreement between X-ray and iDXA assessment. Evaluation of the spine morphometry showed reasonable agreement between iDXA and radiography (ICC for fish-shape, 0.75; for wedge-shape, 0.65; and for compression fractures, 0.70). Bone age determination showed excellent agreement between iDXA and radiography (ICC, 0.97). IDXA-scans of the spine in a pediatric population should be used not only to assess bone mineral density but also to evaluate anatomic structures and vertebral morphometry. Therefore, iDXA can replace some radiographs in children with skeletal diseases. PMID:26059565

  5. Bone tumors in a population of 400 000 insured Swedish dogs up to 10 y of age: incidence and survival

    PubMed Central

    Egenvall, Agneta; Nødtvedt, Ane; von Euler, Henrik

    2007-01-01

    The objectives of this study were to describe the incidence of, survival until, and survival after the diagnosis of canine bone tumors by breed, sex, age, and geographic location of residence. Dogs under 10 y old and insured by a Swedish insurance company between 1995 and 2002 were studied. In total, 764 dogs had claims for bone tumors, and the incidence rate was 5.5 cases per 10 000 dog-years at risk (DYAR). At ages 6, 8, and 10 y, the proportions of dogs with bone tumors were 0.13%, 0.30%, and 0.64%. The top 3 breeds at risk were Irish wolfhound, St. Bernard, and leonberger (incidence rates 99, 78, and 53 cases per 10 000 DYAR, respectively). Median survival time after diagnosis was 56 d in the 419 dogs that survived ≥ 1 d. With a Cox regression model controlling for breed and age, females were shown to be at decreased risk of bone tumors, with a hazard ratio of 0.71 (99% confidence interval 0.58 to 0.87). PMID:17955904

  6. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    SciTech Connect

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  7. Severity and pattern of bone mineral loss in endocrine causes of osteoporosis as compared to age-related bone mineral loss

    PubMed Central

    Dutta, D; Dharmshaktu, P; Aggarwal, A; Gaurav, K; Bansal, R; Devru, N; Garga, UC; Kulshreshtha, B

    2016-01-01

    Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD) loss in endocrinopathies [Graves’ disease (GD), type 1 diabetes mellitus (T1DM), hypogonadotrophic hypogonadism (HypoH), hypergonadotropic hypogonadism (HyperH), hypopituitarism, primary hyperparathyroidism (PHPT)] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO), andropause]. Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done. Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126) were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%), HyperH (85%), and HypoH (79.59%) compared to age-related BMD loss (60.02%; P < 0.001). The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%), HyperH (85%), and HypoH (59.26%) compared to PMO (49.34%; P < 0.001). Z score at LS, TF, NOF, and greater trochanter (GT) was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67%) and HypoH (54.55%) compared to andropause (45.45%; P = 0.001). Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI) and vitamin D. Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting. PMID:27241810

  8. Web-based computer-aided-diagnosis (CAD) system for bone age assessment (BAA) of children

    NASA Astrophysics Data System (ADS)

    Zhang, Aifeng; Uyeda, Joshua; Tsao, Sinchai; Ma, Kevin; Vachon, Linda A.; Liu, Brent J.; Huang, H. K.

    2008-03-01

    Bone age assessment (BAA) of children is a clinical procedure frequently performed in pediatric radiology to evaluate the stage of skeletal maturation based on a left hand and wrist radiograph. The most commonly used standard: Greulich and Pyle (G&P) Hand Atlas was developed 50 years ago and exclusively based on Caucasian population. Moreover, inter- & intra-observer discrepancies using this method create a need of an objective and automatic BAA method. A digital hand atlas (DHA) has been collected with 1,400 hand images of normal children from Asian, African American, Caucasian and Hispanic descends. Based on DHA, a fully automatic, objective computer-aided-diagnosis (CAD) method was developed and it was adapted to specific population. To bring DHA and CAD method to the clinical environment as a useful tool in assisting radiologist to achieve higher accuracy in BAA, a web-based system with direct connection to a clinical site is designed as a novel clinical implementation approach for online and real time BAA. The core of the system, a CAD server receives the image from clinical site, processes it by the CAD method and finally, generates report. A web service publishes the results and radiologists at the clinical site can review it online within minutes. This prototype can be easily extended to multiple clinical sites and will provide the foundation for broader use of the CAD system for BAA.

  9. Functional microimaging: an integrated approach for advanced bone biomechanics and failure analysis

    NASA Astrophysics Data System (ADS)

    Voide, Romain; van Lenthe, G. H.; Schneider, Philipp; Thurner, Philipp J.; Wyss, Peter; Sennhauser, Urs; Stampanoni, Marco; Stauber, Martin; Snedeker, Jess G.; Müller, Ralph

    2006-03-01

    Biomechanical testing is the gold standard to determine bone competence, and has been used extensively. Direct mechanical testing provides detailed information on overall bone mechanical and material properties, but fails in revealing local properties such as local deformations and strains or quantification of fracture progression. Therefore, we incorporated several imaging methods in our mechanical setups in order to get a better insight into bone deformation and failure characteristics. Our aim was to develop an integrative approach for hierarchical investigation of bone, working at different scales of resolution ranging from the whole bone to its ultrastructure. At a macroscopic level, we used high-resolution and high-speed cameras which drastically increased the amount of information obtained from a biomechanical bone test. The new image data proved especially important when dealing with very small bones such as the murine femur. Here the feedback of the camera in the process of aligning and positioning the samples is indispensable for reproducibility. In addition, global failure behavior and fracture initiation can now be visualized with high temporal resolution. At a microscopic level, bone microstructure, i.e. trabecular architecture and cortical porosity, are known to influence bone strength and failure mechanisms significantly. For this reason, we developed an image-guided failure assessment technique, also referred to as functional microimaging, allowing direct time-lapsed 3D visualization and computation of local displacements and strains for better quantification of fracture initiation and progression at the microscopic level. While the resolution of typical desktop micro-computed tomography is around a few micrometers, highly brilliant X-rays from synchrotron radiation permit to explore the nanometer world. This allowed, for the first time, to uncover fully nondestructively the 3D ultrastructure of bone including vascular and cellular structures and to

  10. Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats.

    PubMed Central

    Stitt, A. W.; Li, Y. M.; Gardiner, T. A.; Bucala, R.; Archer, D. B.; Vlassara, H.

    1997-01-01

    Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of proteins and lipids with reducing sugars, have been implicated in many diabetic complications; however, their role in diabetic retinopathy remains largely unknown. Recent studies suggest that the cellular actions of AGEs may be mediated by AGE-specific receptors (AGE-R). We have examined the immunolocalization of AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8 months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2, immunoreactivity (IR) was examined in the complete retinal vascular tree after isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth muscle cells, and endothelial cells of the retinal vessels showed dense intracellular AGE IR. AGE epitopes stained most intensely within pericytes and smooth muscle cells but less in basement membrane of AGE-infused rats compared with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs of vascular endothelial cells, pericytes, and smooth muscle cells of either normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary with each condition. The data indicate that AGEs accumulate as a function of diabetes duration first within the basement membrane and then intracellularly, co-localizing with cellular AGE-Rs. Significant AGE deposits appear within the pericytes after long-term diabetes or acute challenge with AGE infusion conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in retinal cells points to possible interactions of pathogenic significance. Images Figure 1 Figure 2 Figure 3 PMID

  11. Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.

    PubMed

    Lennox, Alanda R; Goodship, Allen E

    2008-02-01

    Some hibernating animals are known to reduce muscle and bone loss associated with mechanical unloading during prolonged immobilisation,compared to humans. However, here we show that wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid significant bone loss altogether, despite six months of continuous hibernation. Using serum biochemical markers of bone turnover, we showed that concentrations for bone resorption are not significantly increased as a consequence of hibernation in wild polar bears. This is in sharp contrast to previous studies on other hibernating species, where for example, black bears (Ursus americanus), show a 3-4 fold increase in serum bone resorption concentrations posthibernation,and must compensate for this loss through rapid bone recovery on remobilisation, to avoid the risk of fracture. In further contrast to black bears, serum concentrations of bone formation markers were highly significantly increased in pregnant female polar bears compared to non-pregnant,thus non-hibernating females both prior to and after hibernation. However, bone formation concentrations in new mothers were significantly reduced compared to pre-hibernation concentrations. The de-coupling of bone turnover in favour of bone formation prior to hibernation, suggests that wild polar bears may posses a unique physiological mechanism for building bone in protective preparation against expected osteopenia associated with disuse,starvation, and hormonal drives to mobilise calcium for reproduction, during hibernation. Understanding this physiological mechanism could have profound implications for a natural solution for the prevention of osteoporosis in animals subjected to captivity with inadequate space for exercise,humans subjected to prolonged bed rest while recovering from illness, or astronauts exposed to antigravity during spaceflight.© 2008 Elsevier Inc. All rights reserved. PMID:18249018

  12. Menopause and Bone Loss

    MedlinePlus

    ... You reach your highest bone mass (size and density) at about age 30. Then, sometime between age ... your bones, your doctor may do a bone density test (DEXA scan). This test gives exact measurements ...

  13. The role of microRNAs in cellular senescence and age-related conditions of cartilage and bone

    PubMed Central

    Weilner, Sylvia; Grillari-Voglauer, Regina; Redl, Heinz; Grillari, Johannes; Nau, Thomas

    2015-01-01

    Background and purpose We reviewed the current state of research on microRNAs in age-related diseases in cartilage and bone. Methods PubMed searches were conducted using separate terms to retrieve articles on (1) the role of microRNAs on aging and tissue degeneration, (2) specific microRNAs that influence cellular and organism senescence, (3) microRNAs in age-related musculoskeletal conditions, and (4) the diagnostic and therapeutic potential of microRNAs in age-related musculoskeletal conditions. Results An increasing number of studies have identified microRNAs associated with cellular aging and tissue degeneration. Specifically in regard to frailty, microRNAs have been found to influence the onset and course of age-related musculoskeletal conditions such as osteoporosis, osteoarthritis, and posttraumatic arthritis. Both intracellular and extracellular microRNAs may be suitable to function as diagnostic biomarkers. In particular Interpretation The research data currently available suggest that microRNAs play an important role in orchestrating age-related processes and conditions of the musculoskeletal system. Further research may help to improve our understanding of the complexity of these processes at the cellular and extracellular level. The option to develop microRNA biomarkers and novel therapeutic agents for the degenerating diseases of bone and cartilage appears to be promising. PMID:25175665

  14. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... section, and (2) Without the presence of any brain, trigeminal ganglia, spinal cord, or dorsal root... brain or trigeminal ganglia tissue, if the vertebral column bones entering the AMR system contain any... bones entering the AMR system for brain, trigeminal ganglia, and spinal cord; the testing of the...

  15. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... section, and (2) Without the presence of any brain, trigeminal ganglia, spinal cord, or dorsal root... brain or trigeminal ganglia tissue, if the vertebral column bones entering the AMR system contain any... bones entering the AMR system for brain, trigeminal ganglia, and spinal cord; the testing of the...

  16. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... section, and (2) Without the presence of any brain, trigeminal ganglia, spinal cord, or dorsal root... brain or trigeminal ganglia tissue, if the vertebral column bones entering the AMR system contain any... bones entering the AMR system for brain, trigeminal ganglia, and spinal cord; the testing of the...

  17. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... section, and (2) Without the presence of any brain, trigeminal ganglia, spinal cord, or dorsal root... brain or trigeminal ganglia tissue, if the vertebral column bones entering the AMR system contain any... bones entering the AMR system for brain, trigeminal ganglia, and spinal cord; the testing of the...

  18. State of Health and Quality of Life of Women at Advanced Age.

    PubMed

    Pinkas, Jarosław; Gujski, Mariusz; Humeniuk, Ewa; Raczkiewicz, Dorota; Bejga, Przemysław; Owoc, Alfred; Bojar, Iwona

    2016-01-01

    BACKGROUND Evaluation of the state of health, quality of life, and relationship between the level of the quality of life and health status in a group of women at advanced age (90 and more years) in Poland. MATERIAL AND METHODS The study was conducted in 2014 in an all-Polish sample of 870 women aged 90 and over. The research instruments were: the author's questionnaire, and standardized tests: Katz index of independence in Activities of Daily Living (ADL), Abbreviated Mental Test Score (AMTS), The World Health Organization Quality of Life (WHOQOL) - BREF. The results of the study were statistically analyzed using significant t test for mean and regression analysis. RESULTS The majority of women at advanced age suffered from chronic pain (76%) and such major geriatric problems as hypoacusis (81%), visual disturbances (69%) and urinary incontinence (60%), the minority - fall and fainting (39%) as well as stool incontinence (17%), severe functional and cognitive impairment (24% and 10% respectively). Women at advanced age assessed positively for overall quality of life (mean 3.3 on 1-5 scale), social relationships (3.5) and environment (3.2), but negatively - general, physical and psychological health (2.7, 2.7 and 2.8 respectively). The presence of chronic pain and major geriatric problems: urinary and stool incontinences, falls and fainting, visual disturbances and hypoacusis significantly decreases overall quality of life, general, physical and psychological health, social relationships and environment of women at advanced age. Overall quality of life, general, physical and psychological health, social relationships and environment correlate to functional and cognitive impairments of women at advanced age. CONCLUSIONS Quality of life of women at advanced age decreased if chronic pain, major geriatric problems as well as functional and cognitive impairments occur. PMID:27580565

  19. Age-related changes in the tooth-bone interface area of acrodont dentition in the chameleon.

    PubMed

    Dosedělová, Hana; Štěpánková, Kateřina; Zikmund, Tomáš; Lesot, Herve; Kaiser, Jozef; Novotný, Karel; Štembírek, Jan; Knotek, Zdeněk; Zahradníček, Oldřich; Buchtová, Marcela

    2016-09-01

    Chameleon teeth develop as individual structures at a distance from the developing jaw bone during the pre-hatching period and also partially during the post-hatching period. However, in the adult, all teeth are fused together and tightly attached to the jaw bone by mineralized attachment tissue to form one functional unit. Tooth to bone as well as tooth to tooth attachments are so firm that if injury to the oral cavity occurs, several neighbouring teeth and pieces of jaw can be broken off. We analysed age-related changes in chameleon acrodont dentition, where ankylosis represents a physiological condition, whereas in mammals, ankylosis only occurs in a pathological context. The changes in hard-tissue morphology and mineral composition leading to this fusion were analysed. For this purpose, the lower jaws of chameleons were investigated using X-ray micro-computed tomography, laser-induced breakdown spectroscopy and microprobe analysis. For a long time, the dental pulp cavity remained connected with neighbouring teeth and also to the underlying bone marrow cavity. Then, a progressive filling of the dental pulp cavity by a mineralized matrix occurred, and a complex network of non-mineralized channels remained. The size of these unmineralized channels progressively decreased until they completely disappeared, and the dental pulp cavity was filled by a mineralized matrix over time. Moreover, the distribution of calcium, phosphorus and magnesium showed distinct patterns in the different regions of the tooth-bone interface, with a significant progression of mineralization in dentin as well as in the supporting bone. In conclusion, tooth-bone fusion in chameleons results from an enhanced production of mineralized tissue during post-hatching development. Uncovering the developmental processes underlying these outcomes and performing comparative studies is necessary to better understand physiological ankylosis; for that purpose, the chameleon can serve as a useful model

  20. A review of recent advances in the assessment of bone porosity, permeability, and interstitial fluid flow

    PubMed Central

    Cardoso, Luis; Fritton, Susannah P.; Gailani, Gaffar; Benalla, Mohammed; Cowin, Stephen C.

    2012-01-01

    This contribution reviews recent research performed to assess the porosity and permeability of bone tissue with the objective of understanding interstitial fluid movement. Bone tissue mechanotransduction is considered to occur due to the passage of interstitial pore fluid adjacent to dendritic cell structures in the lacunar-canalicular porosity. The movement of interstitial fluid is also necessary for the nutrition of osteocytes. This review will focus on four topics related to improved assessment of bone interstitial fluid flow. First, the advantages and limitations of imaging technologies to visualize bone porosities and architecture at several length scales are summarized. Second, recent efforts to measure the vascular porosity and lacunar-canalicular microarchitecture are discussed. Third, studies associated with the measurement and estimation of the fluid pressure and permeability in the vascular and lacunar-canalicular domains are summarized. Fourth, the development of recent models to represent the interchange of fluids between the bone porosities is described. PMID:23174418

  1. Combined Effect of Fetal Sex and Advanced Maternal Age on Pregnancy Outcomes

    PubMed Central

    Weissmann-Brenner, Alina; Simchen, Michal J.; Zilberberg, Eran; Kalter, Anat; Dulitzky, Mordechai

    2015-01-01

    Background Fetal sex and maternal age are each known to affect outcomes of pregnancies. The objective of the present study was to investigate the influence of the combination of maternal age and fetal sex on pregnancy outcomes in term and post-term singleton pregnancies. Material/Methods This was a retrospective study on term singleton pregnancies delivered between 2004 and 2008 at the Chaim Sheba Medical Center. Data collected included maternal age, fetal sex, and maternal and neonatal complications. The combined effect of fetal sex and maternal age on complications of pregnancy was assessed by multivariable logistic regression models. Results The study population comprised 37,327 pregnancies. The risk of operative deliveries increased with maternal age ≥40 and in pregnancies with male fetuses. The risk of maternal diabetes and of longer hospitalization increased as maternal age increased, and in women <40 carrying male fetuses. The risk of hypertensive disorders increased in pregnancies with males as maternal age advanced. The risk of shoulder dystocia and neonatal respiratory complications increased in male neonates born to women<40. The risk of neonatal hypoglycemia increased in males for all maternal ages. Conclusions Risk assessment for fetal sex and advanced maternal age were given for different pregnancy complications. Knowledge of fetal sex adds value to the risk assessment of pregnancies as maternal age increases. PMID:25892459

  2. An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mutual interplay between energy homeostasis and bone metabolism is an important emerging concept. Ghrelin and leptin antagonize each other in regulating energy balance, but the role of this interaction in bone metabolism is unknown. Using ghrelin receptor and leptin-deficient mice, we show that ...

  3. Patients Presenting with Advanced Human Immunodeficiency Virus Disease: Epidemiological Features by Age Group

    PubMed Central

    2016-01-01

    We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross-sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged ≥ 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000-2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease. PMID:26839469

  4. Bone Analyzer

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The danger of disuse osteoporosis under weightless condition in space led to extensive research into measurements of bone stiffness and mass by the Biomedical Research Division of Ames and Stanford University. Through its Technology Utilization Program, NASA funded an advanced SOBSA, a microprocessor-controlled bone probe system. SOBSA determines bone stiffness by measuring responses to an electromagnetic shaker. With this information, a physician can identify bone disease, measure deterioration and prescribe necessary therapy. The system is now undergoing further testing.

  5. Cortical and Trabecular Bone, Bone Mineral Density, and Resistance to ex Vivo Fracture Are Not Altered in Response to Life-Long Vitamin A Supplementation in Aging Rats123

    PubMed Central

    Wray, Amanda E.; Okita, Nori; Ross, A. Catharine

    2011-01-01

    High vitamin A (VA) intakes have been correlated with increased risk of bone fracture. Over 50% of the U.S. adult population reports use of dietary supplements, which can result in VA intakes > 200% of the RDA. In this study, 2 experiments were designed to determine the effect of dietary VA on cortical and trabecular bone properties and resistance to ex vivo fracture. In Expt. 1, we investigated whether orally administered VA accumulates in bone. Seven-week-old rats were treated daily with VA (6 mg/d for 14 d). Total retinol increased in both the tibia and femur (P < 0.01). In Expt. 2, we conducted a longitudinal study in which rats were fed 1 of 3 levels of dietary VA (marginal, adequate, and supplemented, equal to 0.35, 4, and 50 μg retinol/g diet, respectively) from weaning until the ages of 2–3 mo (young), 8–10 mo (middle-age), and 18–20 mo (old). Tibial trabecular and cortical bone structure, bone mineral density, and resistance to fracture were measured using micro-computed tomography and material testing system analysis, respectively. The VA-marginal diet affected measures of cortical bone dimension, suggesting bone remodeling was altered. VA supplementation increased medullary area and decreased cortical thickness in young rats (P < 0.05), but these changes were not present during aging. VA supplementation did not affect resistance to fracture or bone mineral content in old rats. From these results, we conclude that VA-marginal status affects trabecular bone more than cortical bone, and VA supplementation at a moderate level over the lifetime is unlikely to increase the risk of age-related bone fracture in rats. PMID:21310867

  6. Development and evaluation of an aged care specific Advance Care Plan

    PubMed Central

    Silvester, William; Parslow, Ruth A; Lewis, Virginia J; Fullam, Rachael S; Sjanta, Rebekah; Jackson, Lynne; White, Vanessa; Hudson, Rosalie

    2013-01-01

    Objectives To report on the quality of advance care planning (ACP) documents in use in residential aged care facilities (RACF) in areas of Victoria Australia prior to a systematic intervention; to report on the development and performance of an aged care specific Advance Care Plan template used during the intervention. Design An audit of the quality of pre-existing documentation used to record resident treatment preferences and end-of-life wishes at participating RACFs; development and pilot of an aged care specific Advance Care Plan template; an audit of the completeness and quality of Advance Care Plans completed on the new template during a systematic ACP intervention. Participants and setting 19 selected RACFs (managed by 12 aged care organisations) in metropolitan and regional areas of Victoria. Results Documentation in use at facilities prior to the ACP intervention most commonly recorded preferences regarding hospital transfer, life prolonging treatment and personal/cultural/religious wishes. However, 7 of 12 document sets failed to adequately and clearly specify the resident's preferences as regards life prolonging medical treatment. The newly developed aged care specific Advance Care Plan template was met with approval by participating RACFs. Of 203 Advance Care Plans completed on the template throughout the project period, 49% included the appointment of a Medical Enduring Power of Attorney. Requests concerning medical treatment were specified in almost all completed documents (97%), with 73% nominating the option of refusal of life-prolonging treatment. Over 90% of plans included information concerning residents’ values and beliefs, and future health situations that the resident would find to be unacceptable were specified in 78% of completed plans. Conclusions Standardised procedures and documentation are needed to improve the quality of processes, documents and outcomes of ACP in the residential aged care sector. PMID:23626906

  7. Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study.

    PubMed

    Stathopoulos, K D; Zoubos, A B; Papaioannou, N A; Mastrokalos, D; Galanos, A; Papagelopoulos, P J; Skarantavos, G

    2016-01-01

    Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20-79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI) . Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID:27282455

  8. Advancing Age, Advantaged Youth: Parental Age and the Transmission of Resources to Children

    ERIC Educational Resources Information Center

    Powell, Brian; Steelman, Lala Carr; Carini, Robert M.

    2006-01-01

    Using data from the National Education Longitudinal Study of 1988, we identify parental age as influential in the parental provision of economic resources, social capital and cultural capital to adolescents, as well as in parental educational expectations for their children. At the bivariate level, the relationship is curvilinear, suggesting that…

  9. REPLICATION OF LONG BONE LENGTH QTL IN THE F9 - F10 LG,SM ADVANCED INTERCROSS

    PubMed Central

    Norgard, Elizabeth A.; Jarvis, Joseph P.; Roseman, Charles C.; Maxwell, Taylor J.; Kenney-Hunt, Jane P.; Samocha, Kaitlin E.; Pletscher, L. Susan; Wang, Bing; Fawcett, Gloria L.; Leatherwood, Christopher J.; Wolf, Jason B.; Cheverud, James M.

    2009-01-01

    Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F2 intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here, we use the increased resolution of the combined F9 and F10 generations (n=1,455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long bone lengths. Of these, 49 were previously identified in the combined F2-F3 population of this intercross while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect 3-4 long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving 3 F2-F3 QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long bone length. PMID:19306044

  10. Transcutaneous Raman Spectroscopy of Bone

    NASA Astrophysics Data System (ADS)

    Maher, Jason R.

    Clinical diagnoses of bone health and fracture risk typically rely upon measurements of bone density or structure, but the strength of a bone is also dependent upon its chemical composition. One technology that has been used extensively in ex vivo, exposed-bone studies to measure the chemical composition of bone is Raman spectroscopy. This spectroscopic technique provides chemical information about a sample by probing its molecular vibrations. In the case of bone tissue, Raman spectra provide chemical information about both the inorganic mineral and organic matrix components, which each contribute to bone strength. To explore the relationship between bone strength and chemical composition, our laboratory has contributed to ex vivo, exposed-bone animal studies of rheumatoid arthritis, glucocorticoid-induced osteoporosis, and prolonged lead exposure. All of these studies suggest that Raman-based predictions of biomechanical strength may be more accurate than those produced by the clinically-used parameter of bone mineral density. The utility of Raman spectroscopy in ex vivo, exposed-bone studies has inspired attempts to perform bone spectroscopy transcutaneously. Although the results are promising, further advancements are necessary to make non-invasive, in vivo measurements of bone that are of sufficient quality to generate accurate predictions of fracture risk. In order to separate the signals from bone and soft tissue that contribute to a transcutaneous measurement, we developed an overconstrained extraction algorithm that is based upon fitting with spectral libraries derived from separately-acquired measurements of the underlying tissue components. This approach allows for accurate spectral unmixing despite the fact that similar chemical components (e.g., type I collagen) are present in both soft tissue and bone and was applied to experimental data in order to transcutaneously detect, to our knowledge for the first time, age- and disease-related spectral

  11. Dating and context of three middle stone age sites with bone points in the Upper Semliki Valley, Zaire.

    PubMed

    Brooks, A S; Helgren, D M; Cramer, J S; Franklin, A; Hornyak, W; Keating, J M; Klein, R G; Rink, W J; Schwarcz, H; Smith, J N

    1995-04-28

    The extent to which the earliest anatomically modern humans in Africa exhibited behavioral and cognitive traits typical of Homo sapiens sapiens is controversial. In eastern Zaire, archaeological sites with bone points have yielded dates older than 89(-15)+22 thousand years ago by several techniques. These include electron spin resonance, thermoluminescence, optically stimulated luminescence, uranium series, and amino acid racemization. Faunal and stratigraphic data are consistent with this age. PMID:7725099

  12. Ethnic differences in the impact of advanced maternal age on birth prevalence of Down syndrome.

    PubMed Central

    Khoshnood, B; Pryde, P; Wall, S; Singh, J; Mittendorf, R; Lee, K S

    2000-01-01

    OBJECTIVES: This study explored whether ethnic differences in the impact of advanced maternal age on the risk of Down syndrome might reflect differences in use of prenatal diagnostic technologies. METHODS: Maternal age-specific odds of Down syndrome and amniocentesis use were compared among African Americans, Mexican Americans, and non-Hispanic Whites via birth data for the years 1989 to 1991. RESULTS: The odds ratio and population attributable risk of Down syndrome due to maternal age of 35 years or older were highest for Mexican Americans, intermediate for African Americans, and lowest for non-Hispanic Whites. CONCLUSIONS: Advanced maternal age has a greater impact on the risk of Down syndrome for African American and, particularly, Mexican American women than for non-Hispanic White women. This difference in impact might reflect lower availability or use of prenatal diagnostic technologies. PMID:11076250

  13. Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age

    PubMed Central

    Nilsson, Håkan; Bülow, Pia H.; Kazemi, Ali

    2015-01-01

    The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article. PMID:27247673

  14. Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age.

    PubMed

    Nilsson, Håkan; Bülow, Pia H; Kazemi, Ali

    2015-08-01

    The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article. PMID:27247673

  15. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Cancer.gov

    The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

  16. Age estimation based on bone length using 12 regression models of left hand X-ray images for Asian children below 19 years old.

    PubMed

    Darmawan, M F; Yusuf, Suhaila M; Abdul Kadir, M R; Haron, H

    2015-03-01

    Age estimation was used in forensic anthropology to help in the identification of individual remains and living person. However, the estimation methods tend to be unique and applicable only to a certain population. This paper analyzed age estimation using twelve regression models carried out on X-ray images of the left hand taken from an Asian data set for subjects under the age of 19. All the nineteen bones of the left hand were measured using free image software and the statistical analysis were performed using SPSS. There are two methods to determine age in this study which are single bone method and all bones method. For single bone method, S-curve regression model was found to have the highest R-square value using second metacarpal for males, and third proximal phalanx for females. For age estimation using single bone, fifth metacarpal from males and fifth proximal phalanx from females can be used due to the lowest mean square error (MSE) value. To conclude, multiple linear regressions is the best techniques for age estimation in cases where all bones are available, but if not, S-curve regression can be used using single bone method. PMID:25456051

  17. Multi-level characterization of human femoral cortices and their underlying osteocyte network reveal trends in quality of young, aged, osteoporotic and antiresorptive-treated bone.

    PubMed

    Milovanovic, Petar; Zimmermann, Elizabeth A; Riedel, Christoph; vom Scheidt, Annika; Herzog, Lydia; Krause, Matthias; Djonic, Danijela; Djuric, Marija; Püschel, Klaus; Amling, Michael; Ritchie, Robert O; Busse, Björn

    2015-03-01

    Characterization of bone's hierarchical structure in aging, disease and treatment conditions is imperative to understand the architectural and compositional modifications to the material and its mechanical integrity. Here, cortical bone sections from 30 female proximal femurs - a frequent fracture site - were rigorously assessed to characterize the osteocyte lacunar network, osteon density and patterns of bone matrix mineralization by backscatter-electron imaging and Fourier-transform infrared spectroscopy in relation to mechanical properties obtained by reference-point indentation. We show that young, healthy bone revealed the highest resistance to mechanical loading (indentation) along with higher mineralization and preserved osteocyte-lacunar characteristics. In contrast, aging and osteoporosis significantly alter bone material properties, where impairment of the osteocyte-lacunar network was evident through accumulation of hypermineralized osteocyte lacunae with aging and even more in osteoporosis, highlighting increased osteocyte apoptosis and reduced mechanical competence. But antiresorptive treatment led to fewer mineralized lacunae and fewer but larger osteons signifying rejuvenated bone. In summary, multiple structural and compositional changes to the bone material were identified leading to decay or maintenance of bone quality in disease, health and treatment conditions. Clearly, antiresorptive treatment reflected favorable effects on the multifunctional osteocytic cells that are a prerequisite for bone's structural, metabolic and mechanosensory integrity. PMID:25662494

  18. Rethinking end-points for bone-targeted therapy in advanced cancer.

    PubMed

    Gómez García, Susana; Clemons, Mark; Amir, Eitan

    2016-08-01

    The principal objective for any medical therapy is to improve either the duration of life and/or its quality. Metastases in bone can lead to clinically defined events termed skeletal-related events (SREs) which are a quantifiable measure of skeletal morbidity. Avoidance and/or delay of SREs have become the principal objective in trials exploring the efficacy of bone-targeted therapy in patients with skeletal metastases. Despite reductions in the frequency or rate of SRE occurrence, trials of bone-targeted therapy have failed to show any effect on either progression-free or overall survival when compared with placebo or other bone-targeting agents. Similarly, trials of bone-targeted therapy have not shown consistent effects on quality of life. The validity of SRE-based primary outcome measures in cancer clinical trials is therefore, questionable. More novel end-point selection for trials of bone-targeted therapy seems warranted. Composite measures comprising occurrence of symptomatic skeletal events and patient reported outcomes may be an effective solution and warrants further investigation. PMID:27299662

  19. Cosmogenic 10Be constraints on Little Ice Age glacial advances in the eastern Tian Shan, China

    NASA Astrophysics Data System (ADS)

    Li, Yanan; Li, Yingkui; Harbor, Jon; Liu, Gengnian; Yi, Chaolu; Caffee, Marc W.

    2016-04-01

    Presumed Little Ice Age (LIA) glacial advances, represented by a set of fresh, sharp-crested, boulder covered and compact moraines a few hundred meters downstream from modern glaciers, have been widely recognized in the Central Asian highlands. However, few studies have constrained the formation ages of these moraines. We report 31 10Be exposure ages from presumed LIA moraines in six glacial valleys in the Urumqi River headwater area and the Haxilegen Pass area of the eastern Tian Shan, China. Our results reveal that the maximum LIA glacial extent occurred mainly around 430 ± 100 yr, a cold and wet period as indicated by proxy data from ice cores, tree rings, and lake sediments in Central Asia. We also dated a later glacial advance to 270 ± 55 yr. However, 10Be exposure ages on several presumed LIA moraines in front of small, thin glaciers are widely scattered and much older than the globally recognized timing of the LIA. Historical topographic maps indicate that most glaciers were more extensive in the early 1960s, and two of our 10Be sample sites were located close to the ice front at that time. Boulders transported by these small and thin glaciers may be reworked from deposits originally formed prior to the LIA glacial advances, producing apparently old and widely scattered exposure ages due to varied nuclide inheritance. Other published ages indicated an earlier LIA advance around 790 ± 300 yr in the easternmost Tian Shan, but in our study area the more extensive advance around 430 ± 100 yr likely reworked or covered deposits from this earlier event.

  20. The detection of microscopic markers of hemorrhaging and wound age on dry bone: a pilot study.

    PubMed

    Cattaneo, Cristina; Andreola, Salvatore; Marinelli, Eloisa; Poppa, Pasquale; Porta, Davide; Grandi, Marco

    2010-03-01

    An example of the barriers and conceptual differences between forensic anthropology and pathology can be seen in determining the vitality of a wound. Pathology can make use of skin color and microscopic techniques; anthropology (as concerns the study of dry bone) needs different criteria. The diagnosis of the vitality of a wound (whether it is produced antemortem or postmortem) as well as determination of the time elapsed between the production of the wound and death is a crucial issue in forensic pathology. In fresh skin, the red-purplish coloration of a cut or bruise will reveal its vitality, whereas the change in coloration, from a macroscopic perspective, will reveal the time of survival. In more difficult cases, microscopic analyses can be performed. Bone follows similar "laws" as concerns the evolution of the histologic picture, but even if the beginning of healing processes (periosteal bone production and callus formation) can be detected macroscopically and radiologically, these processes require a long time.The scope of this pilot study was therefore to collect bone fractures from cadavers with a known time of survival, have them undergo a simulated putrefaction procedure until they became "dry or macerated bone" and perform macroscopic and microscopic analysis to verify the potential of histology in identifying "vital" processes in putrefied soft-tissue-free bone.A total of 6 samples of fractured bone (cranium, rib, and tibia) were taken from cadavers with known time of survival between trauma and death. Time intervals ranged from a few seconds after the bone fracture had been inflicted, to several hours, days, and weeks. A negative control was included (postmortem fracture). The bone was decalcified and stained with hematoxylin and eosin, Perls' (for the demonstration of hemosiderin deposits), Periodic Acid Schiff, phosphotungstic acid-hematoxylin, and Weigert (for the demonstration of fibrin). Immunohistochemistry was performed using a monoclonal

  1. THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM

    EPA Science Inventory

    THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM (CHC13). A McDonald, Y M Sey and J E Simmons. NHEERL, ORD, U.S. EPA, RTP, NC.
    Disinfection, by chlorination or by ozonation followed by treatment with either chlorine or chloramine, of water containi...

  2. Advances in Disentangling Age, Cohort, and Time Effects: No Quadrature of the Circle, but a Help

    ERIC Educational Resources Information Center

    Masche, J. Gowert; van Dulmen, Manfred H. M.

    2004-01-01

    Based on Schaie's (1965) general developmental model, various data-driven and theory-based approaches to the exploration and disentangling of age, cohort, and time effects on human behavior have emerged. This paper presents and discusses an advancement of data-driven interpretations that stresses parsimony when interpreting the results of…

  3. Advanced BrainAGE in older adults with type 2 diabetes mellitus.

    PubMed

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The "Brain Age Gap Estimation" (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM

  4. A direct role of collagen glycation in bone fracture.

    PubMed

    Poundarik, Atharva A; Wu, Ping-Cheng; Evis, Zafer; Sroga, Grazyna E; Ural, Ani; Rubin, Mishaela; Vashishth, Deepak

    2015-12-01

    Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone's organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagen's ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000-5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk. PMID:26530231

  5. Advanced glycation end products overload might explain intracellular cobalamin deficiency in renal dysfunction, diabetes and aging.

    PubMed

    Obeid, Rima; Shannan, Batool; Herrmann, Wolfgang

    2011-11-01

    Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon. PMID:21880434

  6. Age-Related Adaptation of Bone-PDL-Tooth Complex: Rattus-Norvegicus as a Model System

    PubMed Central

    Leong, Narita L.; Hurng, Jonathan M.; Djomehri, Sabra I.; Gansky, Stuart A.; Ryder, Mark I.; Ho, Sunita P.

    2012-01-01

    Functional loads on an organ induce tissue adaptations by converting mechanical energy into chemical energy at a cell-level. The transducing capacity of cells alters physico-chemical properties of tissues, developing a positive feedback commonly recognized as the form-function relationship. In this study, organ and tissue adaptations were mapped in the bone-tooth complex by identifying and correlating biomolecular expressions to physico-chemical properties in rats from 1.5 to 15 months. However, future research using hard and soft chow over relevant age groups would decouple the function related effects from aging affects. Progressive curvature in the distal root with increased root resorption was observed using micro X-ray computed tomography. Resorption was correlated to the increased activity of multinucleated osteoclasts on the distal side of the molars until 6 months using tartrate resistant acid phosphatase (TRAP). Interestingly, mononucleated TRAP positive cells within PDL vasculature were observed in older rats. Higher levels of glycosaminoglycans were identified at PDL-bone and PDL-cementum entheses using alcian blue stain. Decreasing biochemical gradients from coronal to apical zones, specifically biomolecules that can induce osteogenic (biglycan) and fibrogenic (fibromodulin, decorin) phenotypes, and PDL-specific negative regulator of mineralization (asporin) were observed using immunohistochemistry. Heterogeneous distribution of Ca and P in alveolar bone, and relatively lower contents at the entheses, were observed using energy dispersive X-ray analysis. No correlation between age and microhardness of alveolar bone (0.7±0.1 to 0.9±0.2 GPa) and cementum (0.6±0.1 to 0.8±0.3 GPa) was observed using a microindenter. However, hardness of cementum and alveolar bone at any given age were significantly different (P<0.05). These observations should be taken into account as baseline parameters, during development (1.5 to 4 months), growth (4 to 10 months

  7. Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III

    SciTech Connect

    Gallagher, Carolyn M.; Moonga, Baljit S.; Kovach, John S.

    2010-01-15

    Background: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. Objectives: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal and perimenopausal women aged 42-60 years. Methods: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. Results: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; {beta}=0.45; p{<=}0.05; R{sup 2}=0.35) and low BMI (n=408; {beta}=0.61; p{<=}0.01; R{sup 2}=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd ({beta}=-0.04; p{<=}0.05) and FSH ({beta}=-0.03; p{<=}0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p{<=}0.01). Conclusion: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and both FSH

  8. Breastfeeding and Bone Mass at the Ages of 18 and 30: Prospective Analysis of Live Births from the Pelotas (Brazil) 1982 and 1993 Cohorts

    PubMed Central

    Muniz, Ludmila Correa; Menezes, Ana Maria Baptista; Assunção, Maria Cecília Formoso; Wehrmeister, Fernando Cesar; Martínez-Mesa, Jeovany; Gonçalves, Helen; Domingues, Marlos Rodrigues; Gigante, Denise Petrucci; Horta, Bernardo Lessa; Barros, Fernando C.

    2015-01-01

    Objective To evaluate the effect of total breastfeeding, breastfeeding duration and type of breastfeeding at 3 months of age on bone mass at 18 and 30 years. Study Design A prospective, longitudinal study was conducted with two birth cohorts (1982 and 1993) in Pelotas, Southern Brazil. Measurements of bone mineral content (BMC) and bone mineral density (BMD) at 18 and 30 years of age were obtained by dual-energy X-ray absorptiometry (DXA). Information on breastfeeding was collected during the first 4 years of life. Analyses were performed by linear regression and stratified by sex. Results A total of 1109 and 3226 participants provided complete information on breastfeeding in early life and bone mass at 18 and 30 years, respectively. No association between breastfeeding and bone mass was observed in women at both ages nor among men at age 30. Among men at the age of 18, BMC and BMD were higher among those breastfed regardless of duration (p=0.032 and p=0.043, respectively). Conclusions Despite a very weak positive effect of breastfeeding (yes/no) on BMC and BMD at age 18 in men, most findings pointed to a lack of association between breastfeeding and bone mass until young adulthood. PMID:25880483

  9. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    PubMed Central

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J.

    2014-01-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction. PMID:25387669

  10. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    PubMed

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-12-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80 ± 5.50%, P<0.01) and increased apoptosis (11.31 ± 1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction. PMID:25387669

  11. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    PubMed

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-09-19

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction. PMID:25250588

  12. AGE-RELATED CHANGES IN HUMAN TRABECULAR BONE: RELATIONSHIP BETWEEN MICROSTRUCTURAL STRESS AND STRAIN AND DAMAGE MORPHOLOGY

    PubMed Central

    O’Neal, Jessica M.; Nagaraja, Srinidhi; Diab, Tamim; Vidakovic, Brani; Guldberg, Robert E.

    2011-01-01

    Accumulation of microdamage in aging and disease can cause skeletal fragility and is one of several factors contributing to osteoporotic fractures. To better understand the role of microdamage in fragility fracture, the mechanisms of bone failure must be elucidated on a tissue-level scale where interactions between bone matrix properties, the local biomechanical environment, and bone architecture are concurrently examined for their contributions to microdamage formation. A technique combining histological damage assessment of individual trabeculae with linear finite element solutions of trabecular von Mises and principal stress and strain was used to compare the damage initiation threshold between pre-menopausal (32–37 years, n=3 donors) and post-menopausal (71–80 years, n=3 donors) femoral cadaveric bone. Strong associations between damage morphology and stress and strain parameters were observed in both groups, and an age-related decrease in undamaged trabecular von Mises stress was detected. In trabeculae from younger donors, the 95% CI for von Mises stress on undamaged regions ranged from 50.7 – 67.9 MPa, whereas in trabeculae from older donors, stresses were significantly lower (38.7 – 50.2, p<0.01). Local microarchitectural analysis indicated that thinner, rod-like trabeculae oriented along the loading axis are more susceptible to severe microdamage formation in older individuals, while only rod-like architecture was associated with severe damage in younger individuals. This study therefore provides insight into how damage initiation and morphology relate to local trabecular microstructure and the associated stresses and strains under loading. Furthermore, by comparison of samples from pre- and post-menopausal women, the results suggest that trabeculae from younger individuals can sustain higher stresses prior to microdamage initiation. PMID:21724189

  13. Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo.

    PubMed

    Boerman, Erika M; Everhart, Jesse E; Segal, Steven S

    2016-05-01

    Aging is associated with vascular dysfunction that impairs tissue perfusion, physical activity, and the quality of life. Calcium signaling in endothelial cells (ECs) is integral to vasomotor control, exemplified by localized Ca(2+) signals within EC projections through holes in the internal elastic lamina (IEL). Within these microdomains, endothelium-derived hyperpolarization is integral to smooth muscle cell (SMC) relaxation via coupling through myoendothelial gap junctions. However, the effects of aging on local EC Ca(2+) signals (and thereby signaling between ECs and SMCs) remain unclear, and these events have not been investigated in vivo. Furthermore, it is unknown whether aging affects either the number or the size of IEL holes. In the present study, we tested the hypothesis that local EC Ca(2+) signaling is impaired with advanced age along with a reduction in IEL holes. In anesthetized mice expressing a Ca(2+)-sensitive fluorescent protein (GCaMP2) selectively in ECs, our findings illustrate that for mesenteric arteries controlling splanchnic blood flow the frequency of spontaneous local Ca(2+) signals in ECs was reduced by ∼85% in old (24-26 mo) vs. young (3-6 mo) animals. At the same time, the number (and total area) of holes per square millimeter of IEL was reduced by ∼40%. We suggest that diminished signaling between ECs and SMCs contributes to dysfunction of resistance arteries with advanced age.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-impairs-endothelial-ca2-signaling/. PMID:26945073

  14. CT evaluation of medial clavicular epiphysis as a method of bone age determination in adolescents and young adults

    PubMed Central

    Ufuk, Furkan; Agladioglu, Kadir; Karabulut, Nevzat

    2016-01-01

    PURPOSE We aimed to investigate the use of computed tomography (CT) staging of the medial clavicular epiphysis ossification in forensic bone age determination, and find a CT criterion to determine whether an individual is adult or not. METHODS Chest CT and pulmonary CT angiography exams of 354 patients between 10 and 30 years of age (mean, 21.4 years) were retrospectively evaluated for epiphyseal ossification phase of the bilateral medial clavicles (708 clavicles) and compared with the sex and chronologic age of the individuals. The ossification phase of the medial clavicular epiphyses was classified from stage I to stage V using a modified staging system. RESULTS Epiphyseal ossification center appeared from 11 to 21 years of age. Partial fusion occurred between 16 and 23 years of age. Complete fusion was first achieved at the ages of 18 and 19 years for male and female individuals, respectively. The probability of an individual being ≥18 years old was 70.8% in stage III A and 100% in stages III B, IV, and V in females and males. CONCLUSION CT evaluation of the medial clavicular epiphysis is helpful in forensic age determination and stage III B can be used as a criterion to make the prediction that an individual is older than 18 years. PMID:27015321

  15. Cost-effectiveness of bone densitometry among Caucasian women and men without a prior fracture according to age and body weight

    PubMed Central

    Gourlay, M.; Fink, H. A.; Taylor, B. C.; Orwoll, E. S.; Barrett-Connor, E.; Melton, L. J.; Cummings, S. R.; Ensrud, K. E.

    2013-01-01

    Summary We used a microsimulation model to estimate the threshold body weights at which screening bone densitometry is cost-effective. Among women aged 55–65 years and men aged 55–75 years without a prior fracture, body weight can be used to identify those for whom bone densitometry is cost-effective. Introduction Bone densitometry may be more cost-effective for those with lower body weight since the prevalence of osteoporosis is higher for those with low body weight. Our purpose was to estimate weight thresholds below which bone densitometry is cost-effective for women and men without a prior clinical fracture at ages 55, 60, 65, 75, and 80 years. Methods We used a microsimulation model to estimate the costs and health benefits of bone densitometry and 5 years of fracture prevention therapy for those without prior fracture but with femoral neck osteoporosis (T-score≤−2.5) and a 10-year hip fracture risk of ≥3%. Threshold pre-test probabilities of low BMD warranting drug therapy at which bone densitometry is cost-effective were calculated. Corresponding body weight thresholds were estimated using data from the Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men (MrOS) study, and the National Health and Nutrition Examination Survey (NHANES) for 2005–2006. Results Assuming a willingness to pay of $75,000 per quality adjusted life year (QALY) and drug cost of $500/year, body weight thresholds below which bone densitometry is cost-effective for those without a prior fracture were 74, 90, and 100 kg, respectively, for women aged 55, 65, and 80 years; and were 67, 101, and 108 kg, respectively, for men aged 55, 75, and 80 years. Conclusions For women aged 55–65 years and men aged 55–75 years without a prior fracture, body weight can be used to select those for whom bone densitometry is cost-effective. PMID:22349916

  16. Advanced therapies using autologous bone marrow cells for chronic liver disease.

    PubMed

    Takami, Taro; Terai, Shuji; Sakaida, Isao

    2012-07-01

    The radical treatment currently for decompensated liver cirrhosis is still liver transplantation. However, liver transplants are not widely performed worldwide and development of genuine regeneration therapy for liver cirrhosis is an urgent task. We have developed a novel murine model [the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model], and reported that infused GFP-positive bone marrow cells repopulated cirrhotic liver. Moreover, repopulated bone marrow cells ameliorated liver fibrosis through higher expression of matrix metalloproteinase-9, consistent with improved liver functions and better survival rate. Based on these findings, we started a clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhotic patients, and reported the efficacy and the safety of this approach. On the other hand, various other clinical studies for liver disease have been also reported, including hepatic administration of autologous CD34-positive cells induced by granulocyte colony-stimulating factor (G-CSF), portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow derived mesenchymal stem cells (MSCs). Effectiveness of these approaches has been shown in some patients. We provided here an overview of the current status of liver regeneration therapies including our results of the murine GFP/CCl4 model and ABMi therapy for liver cirrhosis and future prospects. PMID:22846198

  17. The Megavoltage Radiation Therapy in Treatment of Patients With Advanced or Difficult Giant Cell Tumors of Bone

    SciTech Connect

    Ruka, Wlodzimierz; Ptaszynski, Konrad; Bylina, Elzbieta

    2010-10-01

    Purpose: To assess the outcomes of radiotherapy, in terms of local control and treatment complications, of advanced or difficult giant cell tumors of bone (GCTB) that could not be treated by surgery. Methods and Materials: Among 122 consecutive patients with confirmed GCTB from 1985 to 2007, 77 patients were treated by megavoltage radiotherapy because they were inappropriate candidates for surgery. We have performed analysis of all data in terms of progression-free survival (PFS) and treatment morbidity. Median follow-up time was 58 months. Results: In the irradiated group, maximal tumor size ranged from 5 to 18 cm (median, 8.5). Anatomic distribution was as follows: femur, 27 cases; tibia, 19; radial/ulnar bone, 12; sacrum, 9; pelvic bones, 5; other, 5. Twenty-one patients (27%) were referred for local recurrence after {>=}1 other treatment procedures. The radiation doses ranged from 26 to 89 Gy (median, 56; administered 1.8-2.0 Gy/fraction with average total duration of treatment of 5-7 weeks); 8 patients (10%) received <50 Gy. All patients tolerated treatment well without acute or late complications. All patients except two are alive. Local control was achieved in 65 patients (84%; bone recalcification/restitution of joint functions), 12 patients showed signs of local progression, all within irradiated fields (9 were treated successfully with salvage surgery). Five- and 10-year local PFS were 83% and 73%, respectively. Three patients developed lungs metastases. Malignant transformation of GCTB occurred in two patients. Conclusions: GCTB can be safely and effectively treated with megavoltage radiotherapy with local control rate >80% at 5 years. Our study confirms that radiotherapy of GCTB offers an alternative to difficult or complex surgery and may be an option of choice in the treatment of inoperable patients.

  18. Younger Dryas Age advance of Franz Josef Glacier in the Southern Alps of New Zealand

    SciTech Connect

    Denton, G.H. ); Hendy, C.H. )

    1994-06-03

    A corrected radiocarbon age of 11,050 [+-] 14 years before present for an advance of the Franz Josef Glacier to the Waiho Loop terminal moraine on the western flank of New Zealand's Southern Alps shows that glacier advance on a South Pacific island was synchronous with initiation of the Younger Dryas in the North Atlantic region. Hence, cooling at the beginning of the Younger Dryas probably reflects global rather than regional forcing. The source for Younger Dryas climatic cooling may thus lie in the atmosphere rather than in a North Atlantic thermohaline switch. 36 refs., 2 figs., 1 tab.

  19. ROS/redox signaling regulates bone turnover in an age-specific manner in female mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In bone, oxidant signaling through NADPH oxidase (NOX)-derived reactive oxygen species (ROS) superoxide and/or hydrogen peroxide appears to be an important stimulus for osteoclast differentiation and activity. ROS signaling has been suggested to increase RANKL mRNA and protein expression, thus enha...

  20. Effects of bone-specific physical activity, gender and maturity on tibial cross-sectional bone material distribution: a cross-sectional pQCT comparison of children and young adults aged 5-29 years.

    PubMed

    Rantalainen, Timo; Weeks, Benjamin K; Nogueira, Rossana C; Beck, Belinda R

    2015-03-01

    Growth is the opportune time to modify bone accrual. While bone adaptation is known to be dependent on local loading and consequent deformations (strain) of bone, little is known about the effects of sex, and bone-specific physical activity on location-specific cross-sectional bone geometry during growth. To provide more insight we examined bone traits at different locations around tibial cross sections, and along the tibia between individuals who vary in terms of physical activity exposure, sex, and pubertal status. Data from 304 individuals aged 5-29 years (172 males, 132 females) were examined. Peripheral quantitative computed tomography (pQCT) was applied at 4%, 14%, 38%, and 66% of tibial length. Maturity was established by estimating age at peak height velocity (APHV). Loading history was quantified with the bone-specific physical activity questionnaire (BPAQ). Comparisons, adjusted for height, weight and age were made between sex, maturity, and BPAQ tertile groups. Few to no differences were observed between sexes or BPAQ tertiles prior to APHV, whereas marked sexual dimorphism and differences between BPAQ tertiles were observed after APHV. Cross-sectional location-specific differences between BPAQ tertiles were not evident prior to APHV, whereas clear location-specificity was observed after APHV. In conclusion, the skeletal benefits of physical activity are location-specific in the tibia. The present results indicate that the peri- or post-pubertal period is likely a more favourable window of opportunity for enhancing cross-sectional bone geometry than pre-puberty. Increased loading during the peri-pubertal period may enhance the bone of both sexes. PMID:25465388

  1. Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease.

    PubMed Central

    Mufson, E J; Kordower, J H

    1992-01-01

    Using a monoclonal antibody directed against the primate nerve growth factor (NGF) receptor, we examined the expression of NGF receptors within neuronal perikarya of normal adult human cerebral cortex (27-98 years old) and individuals with Alzheimer disease (AD). This expression of cortical NGF receptors was compared with that seen in other neurological diseases and normal human development as well as in young and aged nonhuman primates. NGF receptor-containing cortical neurons were not observed in young adults (less than 50 years old) and were observed only infrequently in non-demented elderly individuals (50-80 years old). In contrast, numerous NGF receptor-containing cortical neurons were seen in AD patients of all ages and in one 98-year-old nondemented patient. In advanced age and AD, numerous NGF receptor-positive neurons were located within laminae II-VI of temporal association cortices whereas only a few were seen in the subicular complex, entorhinal cortex, parahippocampal gyrus, and amygdaloid complex. These perikarya appeared healthy, with bipolar, fusiform, or multipolar morphologies and extended varicose dendritic arbors. These neurons failed to express neurofibrillary tangle-bearing material. In contrast to AD, NGF receptor-containing cortical neurons were not observed in Parkinson disease, Pick disease, or Shy-Drager syndrome. The NGF receptor-containing cortical neurons seen in advanced age and AD were similar in morphology to those observed in human fetal cortex. No NGF receptor-containing cortical neurons were observed in young or aged nonhuman primates. These findings suggest that neurons within the human cerebral cortex exhibit plasticity in their expression of NGF receptors in AD and extreme advanced aging. Images PMID:1309947

  2. Short-term exercise-induced improvements in bone properties are for the most part not maintained during aging in hamsters.

    PubMed

    Koistinen, Arto P; Halmesmäki, Esa P; Iivarinen, Jarkko T; Arokoski, Jari P A; Brama, Pieter A J; Jurvelin, Jukka S; Helminen, Heikki J; Isaksson, Hanna

    2014-03-01

    Physical exercise during growth affects composition, structure and mechanical properties of bone. In this study we investigated whether the beneficial effects of exercise during the early growth phase have long-lasting effects or not. Female Syrian golden hamsters (total n=152) were used in this study. Half of the hamsters had access to running wheels during their rapid growth phase (from 1 to 3months of age). The hamsters were sacrificed at the ages of 1, 3, 12, and 15months. The diaphysis of the mineralized humerus was analyzed with microCT and subjected to three-point-bending mechanical testing. The trabecular bone in the tibial metaphysis was also analyzed with microCT. The collagen matrix of the humerus bone was studied by tensile testing after decalcification. The weight of the hamsters as well as the length of the bone and the volumetric bone mineral density (BMDvol) of the humerus was higher in the running group at the early age (3months). Moreover, the mineralized bone showed improved mechanical properties in humerus and had greater trabecular thickness in the subchondral bone of tibia in the runners. However, by the age of 12 and 15months, these differences were equalized with the sedentary group. The tensile strength and Young's modulus of decalcified humerus were higher in the runners at early stage, indicating a stronger collagen network. In tibial metaphysis, trabecular thickness was significantly higher for the runners in the old age groups (12 and 15months). Our study demonstrates that physical exercise during growth improves either directly or indirectly through weight gain bone properties of the hamsters. However, the beneficial effects were for the most part not maintained during aging. PMID:24423444

  3. Phenomenal advanced age of pupping in a captive Pacific harbor seal (Phoca vitulina richardsi).

    PubMed

    Temte, Jonathan L; Flynn, Erin

    2015-11-01

    To better define the life history in the captive environment, we describe the reproductive history and advanced age of pupping of a female Pacific harbor seal (Phoca vitulina richardsi) at the Henry Vilas Zoo (HVZ) in Madison, Wisconsin. This female gave birth to a viable pup on May 16, 2012, at the age of 42 years and is the oldest documented birth reported for this species. This female also demonstrated high temporal fidelity to her previously described birth timing. The pup's sire was also 42 years at the time of birth. Captive harbor seals can remain reproductively healthy into their 5th decade. PMID:26452165

  4. Reactive Oxygen Species Limit the Ability of Bone Marrow Stromal Cells to Support Hematopoietic Reconstitution in Aging Mice

    PubMed Central

    Khatri, Rahul; Krishnan, Shyam; Roy, Sushmita; Chattopadhyay, Saborni; Kumar, Vikash

    2016-01-01

    Aging of organ and abnormal tissue regeneration are recurrent problems in physiological and pathophysiological conditions. This is most crucial in case of high-turnover tissues, like bone marrow (BM). Using reciprocal transplantation experiments in mouse, we have shown that self-renewal potential of hematopoietic stem and progenitor cells (HSPCs) and BM cellularity are markedly influenced with the age of the recipient mice rather than donor mice. Moreover, accumulation of excessive reactive oxygen species (ROS) in BM stromal cells compared to HSPC compartment, in time-dependent manner, suggests that oxidative stress is involved in suppression of BM cellularity by affecting microenvironment in aged mice. Treatment of these mice with a polyphenolic antioxidant curcumin is found to partially quench ROS, thereby rescues stromal cells from oxidative stress-dependent cellular injury. This rejuvenation of stromal cells significantly improves hematopoietic reconstitution in 18-month-old mice compared to age control mice. In conclusion, this study implicates the role of ROS in perturbation of stromal cell function upon aging, which in turn affects BM's reconstitution ability in aged mice. Thus, a rejuvenation therapy using curcumin, before HSPC transplantation, is found to be an efficient strategy for successful marrow reconstitution in older mice. PMID:27140293

  5. Sleepwalking Into Infertility: The Need for a Public Health Approach Toward Advanced Maternal Age.

    PubMed

    Lemoine, Marie-Eve; Ravitsky, Vardit

    2015-01-01

    In Western countries today, a growing number of women delay motherhood until their late 30s and even 40s, as they invest time in pursuing education and career goals before starting a family. This social trend results from greater gender equality and expanded opportunities for women and is influenced by the availability of contraception and assisted reproductive technologies (ART). However, advanced maternal age is associated with increased health risks, including infertility. While individual medical solutions such as ART and elective egg freezing can promote reproductive autonomy, they entail significant risks and limitations. We thus argue that women should be better informed regarding the risks of advanced maternal age and ART, and that these individual solutions need to be supplemented by a public health approach, including policy measures that provide women with the opportunity to start a family earlier in life without sacrificing personal career goals. PMID:26575814

  6. Advances in bone surgery: the Er:YAG laser in oral surgery and implant dentistry

    PubMed Central

    Stübinger, Stefan

    2010-01-01

    The erbium-doped yttrium aluminium garnet (Er:YAG) laser has emerged as a possible alternative to conventional methods of bone ablation because of its wavelength of 2.94 μm, which coincides with the absorption peak of water. Over the last decades in several experimental and clinical studies, the widespread initial assumption that light amplification for stimulated emission of radiation (laser) osteotomy inevitably provokes profound tissue damage and delayed wound healing has been refuted. In addition, the supposed disadvantage of prolonged osteotomy times could be overcome by modern short-pulsed Er:YAG laser systems. Currently, the limiting factors for a routine application of lasers for bone ablation are mainly technical drawbacks such as missing depth control and a difficult and safe guidance of the laser beam. This article gives a short overview of the development process and current possibilities of noncontact Er:YAG laser osteotomy in oral and implant surgery. PMID:23662082

  7. Advancing maternal age and trisomy screening: the practice challenges of facilitating choice and gaining consent.

    PubMed

    Birt, Maria

    2015-12-01

    Antenatal screening for chromosomal anomalies such as Trisomy 13, 18 and 21 (Patau's, Edward's and Down's syndrome respectively) is offered to all pregnant women in the first two trimesters.This article explores the varying considerations of consent for this type of screening, particularly in relation to women of advancing age who are at increased risk of carrying a pregnancy affected by a trisomy. The practical challenges or barriers of gaining valid, meaningful informed consent are discussed. PMID:26753259

  8. Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies

    PubMed Central

    Passaro, Antonio; Gori, Bruno; Del Signore, Ester; Migliorino, Maria Rita; Ricciardi, Serena; Fulvi, Alberto; de Marinis, Filippo

    2014-01-01

    Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is followed by a response rate of 70–80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. This review is focused on the evidence for therapeutic strategies in bone and brain metastases due to lung cancer. PMID:24790650

  9. Self-reported ballet classes undertaken at age 10-12 years and hip bone mineral density in later life.

    PubMed

    Khan, K M; Bennell, K L; Hopper, J L; Flicker, L; Nowson, C A; Sherwin, A J; Crichton, K J; Harcourt, P R; Wark, J D

    1998-01-01

    The major effect of weightbearing exercise on adult bone mass may be exerted during childhood. We examined the relationship between reported hours of ballet classes per week undertaken as a child and adult bone mineral density (BMD) at the hip, spine, and forearm. We performed a retrospective cohort study in 99 female retired dancers (mean age 51 years, SD 14 years) and 99 normal controls, derived from a twin study, matched hierarchically for age, height, weight and menopausal status. Starting age of ballet was recalled and weekly hours of ballet as a child was self-reported on two occasions. BMD was measured using dualenergy X-ray absorptiometry and reported as a Z-score. Self-reported hours of ballet class undertaken per week at each age between 10 and 12 years was positively associated with a difference in BMD between dancers and controls at both the femoral neck site (beta = 0.73, p = 0.001) and the total hip site (beta = 0.55, p < 0.01). These associations were unaffected by adjustment for covariates including measures of adult activity (current physical activity, years of fulltime ballet), measures of menstrual disturbance (age of menarche, history of irregular menses), dietary history (calcium intake as a child, adolescent or adult) or lifestyle factors (lifetime smoking, lifetime alcohol). Although starting age of ballet was negatively associated with weight-adjusted within-pair hip BMD difference, it was no longer associated after adjustment for weekly hours of ballet. There was no relationship between hours of ballet undertaken as a child and differences in BMD at the lumbar spine or upper limb, at any age. Our data suggest that classical ballet classes undertaken between the ages of 10 and 12 years are independently and positively associated with a difference in hip BMD between dancers and controls. The findings are consistent with the hypothesis that this age range identifies a stage of development when the proximal femur is particularly responsive to

  10. Reference Values of Impulse Oscillometric Lung Function Indices in Adults of Advanced Age

    PubMed Central

    Schulz, Holger; Flexeder, Claudia; Behr, Jürgen; Heier, Margit; Holle, Rolf; Huber, Rudolf M.; Jörres, Rudolf A.; Nowak, Dennis; Peters, Annette; Wichmann, H.-Erich; Heinrich, Joachim; Karrasch, Stefan

    2013-01-01

    Background Impulse oscillometry (IOS) is a non-demanding lung function test. Its diagnostic use may be particularly useful in patients of advanced age with physical or mental limitations unable to perform spirometry. Only few reference equations are available for Caucasians, none of them covering the old age. Here, we provide reference equations up to advanced age and compare them with currently available equations. Methods IOS was performed in a population-based sample of 1990 subjects, aged 45–91 years, from KORA cohorts (Augsburg, Germany). From those, 397 never-smoking, lung healthy subjects with normal spirometry were identified and sex-specific quantile regression models with age, height and body weight as predictors for respiratory system impedance, resistance, reactance, and other parameters of IOS applied. Results Women (n = 243) showed higher resistance values than men (n = 154), while reactance at low frequencies (up to 20 Hz) was lower (p<0.05). A significant age dependency was observed for the difference between resistance values at 5 Hz and 20 Hz (R5–R20), the integrated area of low-frequency reactance (AX), and resonant frequency (Fres) in both sexes whereas reactance at 5 Hz (X5) was age dependent only in females. In the healthy subjects (n = 397), mean differences between observed values and predictions for resistance (5 Hz and 20 Hz) and reactance (5 Hz) ranged between −1% and 5% when using the present model. In contrast, differences based on the currently applied equations (Vogel & Smidt 1994) ranged between −34% and 76%. Regarding our equations the indices were beyond the limits of normal in 8.1% to 18.6% of the entire KORA cohort (n = 1990), and in 0.7% to 9.4% with the currently applied equations. Conclusions Our study provides up-to-date reference equations for IOS in Caucasians aged 45 to 85 years. We suggest the use of the present equations particularly in advanced age in order to detect airway dysfunction. PMID

  11. Detection of advanced glycation end products (AGEs) on human skin by in vivo confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Martin, A. A.; Pereira, L.; Ali, S. M.; Pizzol, C. D.; Tellez, C. A.; Favero, P. P.; Santos, L.; da Silva, V. V.; Praes, C. E. O.

    2016-03-01

    The aging process involves the reduction in the production of the major components of skin tissue. During intrinsic aging and photoaging processes, in dermis of human skin, fibroblasts become senescent and have decreased activity, which produce low levels of collagen. Moreover, there is accumulation of advanced glycation end products (AGEs). AGEs have incidence in the progression of age-related diseases, principally in diabetes mellitus and in Alzheimer's diseases. AGEs causes intracellular damage and/or apoptosis leading to an increase of the free radicals, generating a crosslink with skin proteins and oxidative stress. The aim of this study is to detect AGEs markers on human skin by in vivo Confocal Raman spectroscopy. Spectra were obtained by using a Rivers Diagnostic System, 785 nm laser excitation and a CCD detector from the skin surface down to 120 μm depth. We analyzed the confocal Raman spectra of the skin dermis of 30 women volunteers divided into 3 groups: 10 volunteers with diabetes mellitus type II, 65-80 years old (DEW); 10 young healthy women, 20-33 years old (HYW); and 10 elderly healthy women, 65-80 years old (HEW). Pentosidine and glucosepane were the principally identified AGEs in the hydroxyproline and proline Raman spectral region (1000-800 cm-1), in the 1.260-1.320 cm-1 region assignable to alpha-helical amide III modes, and in the Amide I region. Pentosidine and glucosepane calculated vibrational spectra were performed through Density Functional Theory using the B3LYP functional with 3-21G basis set. Difference between the Raman spectra of diabetic elderly women and healthy young women, and between healthy elderly women and healthy young women were also obtained with the purpose of identifying AGEs Raman bands markers. AGEs peaks and collagen changes have been identified and used to quantify the glycation process in human skin.

  12. Age- and direction-related adaptations of lumbar vertebral trabecular bone with respect to apparent stiffness and tissue level stress distribution

    NASA Astrophysics Data System (ADS)

    Gong, He; Fan, Yubo; Zhang, Ming; Qin, Ling

    2009-02-01

    The objective of this study was to study the age-related adaptation of lumbar vertebral trabecular bone at the apparent level, as well as the tissue level in three orthogonal directions. Ninety trabecular specimens were obtained from six normal L4 vertebral bodies of six male cadavers in two age groups, three aged 62 years and three aged 69 years, and were scanned using a high-resolution micro-computed tomography (micro-CT) system, then converted to micro-finite element models to do micro-finite element analyses. The relationship between apparent stiffness and bone volume fraction, and the tissue level von Mises stress distribution for each trabecular specimen when compressed separately in the longitudinal direction, medial-lateral and anterior-posterior directions (transverse directions) were derived and compared between two age groups. The results showed that at the apparent level, trabecular bones from 69-year group had stiffer bone structure relative to their volume fractions in all three directions, and in both age groups, changes in bone volume fraction could explain more variations in apparent stiffness in the longitudinal direction than the transverse directions; at the tissue level, aging had little effect on the tissue von Mises stress distributions for the compressions in all the three directions. The novelty of the present study was that it provided quantitative assessments on the age and direction-related adaptation of Chinese male lumbar vertebral trabecular bone from two different levels: stiffness at the apparent level and stress distribution at the tissue level. It may help to understand the failure mechanisms and fracture risks of vertebral body associated with aging and direction for the prevention of fracture risks in elder individuals.

  13. Surgical advances in bone and soft tissue sarcoma: 50 years of progress.

    PubMed

    Henshaw, Robert M

    2014-01-01

    As the American Society of Clinical Oncology celebrates its 50th anniversary, physicians can appreciate the significant advances made in the treatment of patients with sarcoma. Historically, these rare tumors have garnered great interest in the medical profession, due to their ability to reach extraordinary size, resulting in substantial deformities and disabilities. Fortunately, advances in surgical management, which have occurred concurrently with advances in imaging, diagnostic techniques, and both local and systemic adjuvant treatments, offer patients diagnosed with sarcoma significant hope for successful treatment and the expectation of a meaningful quality of life. PMID:24857083

  14. [Information theory of ageing: studying the effect of bone marrow transplantation on the life span of mice].

    PubMed

    Karnaukhov, A V; Karnaukhova, E V; Sergievich, L A; Karnaukhova, N A; Karnaukhova, N A; Bogdanenko, E V; Smirnov, A A; Manokhina, I A; Karnaukhov, V N

    2014-01-01

    In this paper the method of life span extension of multicellular organisms (human) using the reservation of stem cells followed by autotransplantation has been proposed. As the efficiency of this method results from the information theory of ageing, it is important to verify it experimentally testing the basic concepts of the theory. Taking it into consideration, the experiment on the bone marrow transplantation to old mice from young closely-related donors of the inbred line was carried out. It has been shown, that transplanted animals exhibited a survival advantage, a mean life span increased by 34% as compared to the control. This result not only demonstrates the efficiency of the proposed method for life span extension of multicellular organisms, but also confirms the basis of the information theory of ageing. PMID:25707248

  15. Relationship between exercise and bone mineral density among over 5,000 women aged 40 years and above.

    PubMed

    Kano, K

    1998-03-01

    An epidemiological survey was conducted to clarify the relationship between bone mineral density(BMD) and exercise at 14 health centers in Ibaraki Prefecture, Japan from September 1994 through March 1995. More than 5,000 women participated in this survey. Second metacarpal BMD was measured by CXD(Computed X-ray Densitometry) method. Information about past history of exercise was obtained by questionnaire. sigma GS/D < 2.3(sigma GS/D: a parameter of BMD) was used to estimate the suspicion of osteoporosis. Data on 5,124 women aged 40 years and above were analyzed. Subjects were categorized into two groups according to the presence(n = 1,687) or absence(n = 3,437) of past history of regular exercise. sigma GS/D values were significantly (p < or = 0.05) higher in women who have had regular exercise in the past than those of the non-exercise group except those aged over 70 years. Ball game, foot sports and gymnastics were the main exercises. When osteoporosis was suspected based on the measurements of bone mineral density, the odds ratio (exercise present/absent) was 0.27 (95% confidence limits: 0.08-0.94), 0.82 (0.65-1.04), 0.78 (0.61-0.99), and 1.25 (0.67-2.35) at 40-49, 50-59, 60-69, and over 70 years, respectively. The results of the present study suggest the beneficial influence of exercise on bone mineral density and its utility for preventing osteoporosis. PMID:9575692

  16. Determining 'age at death' for forensic purposes using human bone by a laboratory-based biomechanical analytical method.

    PubMed

    Zioupos, P; Williams, A; Christodoulou, G; Giles, R

    2014-05-01

    Determination of age-at-death (AAD) is an important and frequent requirement in contemporary forensic science and in the reconstruction of past populations and societies from their remains. Its estimation is relatively straightforward and accurate (±3yr) for immature skeletons by using morphological features and reference tables within the context of forensic anthropology. However, after skeletal maturity (>35yr) estimates become inaccurate, particularly in the legal context. In line with the general migration of all the forensic sciences from reliance upon empirical criteria to those which are more evidence-based, AAD determination should rely more-and-more upon more quantitative methods. We explore here whether well-known changes in the biomechanical properties of bone and the properties of bone matrix, which have been seen to change with age even after skeletal maturity in a traceable manner, can be used to provide a reliable estimate of AAD. This method charts a combination of physical characteristics some of which are measured at a macroscopic level (wet & dry apparent density, porosity, organic/mineral/water fractions, collagen thermal degradation properties, ash content) and others at the microscopic level (Ca/P ratios, osteonal and matrix microhardness, image analysis of sections). This method produced successful age estimates on a cohort of 12 donors of age 53-85yr (7 male, 5 female), where the age of the individual could be approximated within less than ±1yr. This represents a vastly improved level of accuracy than currently extant age estimation techniques. It also presents: (1) a greater level of reliability and objectivity as the results are not dependent on the experience and expertise of the observer, as is so often the case in forensic skeletal age estimation methods; (2) it is purely laboratory-based analytical technique which can be carried out by someone with technical skills and not the specialised forensic anthropology experience; (3) it can

  17. Feature description with SIFT, SURF, BRIEF, BRISK, or FREAK? A general question answered for bone age assessment.

    PubMed

    Kashif, Muhammad; Deserno, Thomas M; Haak, Daniel; Jonas, Stephan

    2016-01-01

    Solving problems in medical image processing is either generic (being applicable to many problems) or specific (optimized for a certain task). For example, bone age assessment (BAA) on hand radiographs is a frequent but cumbersome task for radiologists. For this problem, many specific solutions have been proposed. However, general-purpose feature descriptors are used in many computer vision applications. Hence, the aim of this study is (i) to compare the five leading keypoint descriptors on BAA, and, in doing so, (ii) presenting a generic approach for a specific task. Two methods for keypoint selection were applied: sparse and dense feature points. For each type, SIFT, SURF, BRIEF, BRISK, and FREAK feature descriptors were extracted within the epiphyseal regions of interest (eROI). Classification was performed using a support vector machine. Reference data (1101 radiographs) of the University of Southern California was used for 5-fold cross-validation. The data was grouped into 30 classes representing the bone age range of 0-18 years. With a mean error of 0.605 years, dense SIFT gave best results and outperforms all published methods. The accuracy was 98.36% within the range of 2 years. Dense SIFT represents a generic method for a specific question. PMID:26623943

  18. Bone Mineral Density in Gravida: Effect of Pregnancies and Breast-Feeding in Women of Differing Ages and Parity

    PubMed Central

    Mishukov, Yuri; Babchenko, Liana; Samueloff, Arnon; Zimran, Ari

    2014-01-01

    Changes of bone during pregnancy and during lactation evaluated by bone mineral density (BMD) may have implications for risk of osteoporosis and fractures. We studied BMD in women of differing ages, parity, and lactation histories immediately postpartum for BMD, T-scores, and Z-scores. Institutional Review Board approval was received. All women while still in hospital postpartum were asked to participate. BMD was performed by dual-energy X-ray absorptiometry (DXA) machine at femoral neck (FN) and lumbar spine (LS) by a single technician. Of 132 participants, 73 (55.3%) were ≤30 years; 27 (20.5%) were primiparous; 36 (27.3%) were grand multiparous; 35 (26.5%) never breast fed. Mean FN T-scores and Z-scores were higher than respective mean LS scores, but all means were within the normal limits. Mean LS T-scores and Z-scores were highest in the grand multiparas. There were only 2 (1.5%) outliers with low Z-scores. We conclude that, in a large cohort of Israeli women with BMD parameters assessed by DXA within two days postpartum, mean T-scores and Z-scores at both the LS and FN were within normal limits regardless of age (20–46 years), parity (1–13 viable births), and history of either no or prolonged months of lactation (up to 11.25 years). PMID:25506038

  19. Bone mineral density in gravida: effect of pregnancies and breast-feeding in women of differing ages and parity.

    PubMed

    Lebel, Ehud; Mishukov, Yuri; Babchenko, Liana; Samueloff, Arnon; Zimran, Ari; Elstein, Deborah

    2014-01-01

    Changes of bone during pregnancy and during lactation evaluated by bone mineral density (BMD) may have implications for risk of osteoporosis and fractures. We studied BMD in women of differing ages, parity, and lactation histories immediately postpartum for BMD, T-scores, and Z-scores. Institutional Review Board approval was received. All women while still in hospital postpartum were asked to participate. BMD was performed by dual-energy X-ray absorptiometry (DXA) machine at femoral neck (FN) and lumbar spine (LS) by a single technician. Of 132 participants, 73 (55.3%) were ≤30 years; 27 (20.5%) were primiparous; 36 (27.3%) were grand multiparous; 35 (26.5%) never breast fed. Mean FN T-scores and Z-scores were higher than respective mean LS scores, but all means were within the normal limits. Mean LS T-scores and Z-scores were highest in the grand multiparas. There were only 2 (1.5%) outliers with low Z-scores. We conclude that, in a large cohort of Israeli women with BMD parameters assessed by DXA within two days postpartum, mean T-scores and Z-scores at both the LS and FN were within normal limits regardless of age (20-46 years), parity (1-13 viable births), and history of either no or prolonged months of lactation (up to 11.25 years). PMID:25506038

  20. Growth and Potential Damage of Human Bone-Derived Cells Cultured on Fresh and Aged C60/Ti Films

    PubMed Central

    Kopova, Ivana; Lavrentiev, Vasily; Vacik, Jiri; Bacakova, Lucie

    2015-01-01

    Thin films of binary C60/Ti composites, with various concentrations of Ti ranging from ~ 25% to ~ 70%, were deposited on microscopic glass coverslips and were tested for their potential use in bone tissue engineering as substrates for the adhesion and growth of bone cells. The novelty of this approach lies in the combination of Ti atoms (i.e., widely used biocompatible material for the construction of stomatological and orthopedic implants) with atoms of fullerene C60, which can act as very efficient radical scavengers. However, fullerenes and their derivatives are able to generate harmful reactive oxygen species and to have cytotoxic effects. In order to stabilize C60 molecules and to prevent their possible cytotoxic effects, deposition in the compact form of Ti/C60 composites (with various Ti concentrations) was chosen. The reactivity of C60/Ti composites may change in time due to the physicochemical changes of molecules in an air atmosphere. In this study, we therefore tested the dependence between the age of C60/Ti films (from one week to one year) and the adhesion, morphology, proliferation, viability, metabolic activity and potential DNA damage to human osteosarcoma cells (lines MG-63 and U-2 OS). After 7 days of cultivation, we did not observe any negative influence of fresh or aged C60/Ti layers on cell behavior, including the DNA damage response. The presence of Ti atoms resulted in improved properties of the C60 layers, which became more suitable for cell cultivation. PMID:25875338

  1. Translating Advances from the Basic Biology of Aging into Clinical Application

    PubMed Central

    Kirkland, James L.

    2013-01-01

    Recently, lifespan and healthspan have been extended in experimental animals using interventions that are potentially translatable into humans. A great deal of thought and work are needed beyond the usual steps in drug development to advance these findings into clinical application. Realistic pre-clinical and clinical trials paradigms need to be devised. Focusing on subjects with symptoms of age-related diseases or frailty or who are at imminent risk of developing these problems, measuring effects on short-term, clinically relevant outcomes, as opposed to long-term outcomes such as healthspan or lifespan, and developing biomarkers and outcome measures acceptable to regulatory agencies will be important. Research funding is a major roadblock, as is lack of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and conducting investigational new drug clinical trials. Options are reviewed for developing a path from the bench to the bedside for interventions that target fundamental aging processes. PMID:23237984

  2. Advanced age negatively impacts survival in an experimental brain tumor model.

    PubMed

    Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

    2016-09-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. PMID:27493076

  3. Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

    PubMed

    Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

    2014-08-01

    While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

  4. Interactive effects of vascular risk burden and advanced age on cerebral blood flow

    PubMed Central

    Bangen, Katherine J.; Nation, Daniel A.; Clark, Lindsay R.; Harmell, Alexandrea L.; Wierenga, Christina E.; Dev, Sheena I.; Delano-Wood, Lisa; Zlatar, Zvinka Z.; Salmon, David P.; Liu, Thomas T.; Bondi, Mark W.

    2014-01-01

    Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines. PMID:25071567

  5. Effects of advanced aging on the neural correlates of successful recognition memory

    PubMed Central

    Wang, Tracy H.; Kruggel, Frithjof; Rugg, Michael D.

    2009-01-01

    Functional neuroimaging studies have reported that the neural correlates of retrieval success (old>new effects) are larger and more widespread in older than in young adults. In the present study we investigated whether this pattern of age-related ‘over-recruitment’ continues into advanced age. Using functional magnetic resonance imaging (fMRI), retrieval-related activity from two groups (N = 18 per group) of older adults aged 84–96 yrs (‘old-old’) and 64–77 yrs (‘young-old’) was contrasted. Subjects studied a series of pictures, half of which were presented once, and half twice. At test, subjects indicated whether each presented picture was old or new. Recognition performance of the old-old subjects for twice-studied items was equivalent to that of the young-old subjects for once-studied items. Old>new effects common to the two groups were identified in several cortical regions, including medial and lateral parietal and prefrontal cortex. There were no regions where these effects were of greater magnitude in the old-old group, and thus no evidence of over-recruitment in this group relative to the young-old individuals. In one region of medial parietal cortex, effects were greater (and only significant) in the young-old group. The failure to find evidence of over-recruitment in the old-old subjects relative to the young-old group, despite their markedly poorer cognitive performance, suggests that age-related over-recruitment effects plateau in advanced age. The findings for the medial parietal cortex underscore the sensitivity of this cortical region to increasing age. PMID:19428399

  6. Intraperitoneal Follicular Dendritic Cell Sarcoma: Role of Chemotherapy and Bone Marrow Allotransplantation in Locally Advanced Disease?

    PubMed Central

    Liberale, G; Keriakos, K; Azerad, MA; De Saint Aubain, N; El Nakadi, I

    2015-01-01

    We describe a case of a 44 year-old woman diagnosed with follicular dendritic cell sarcoma (FDCS). FDCS is a very rare disease affecting the dendritic antigen presenting cells and is often misdiagnosed. Surgery is considered the best treatment modality, followed by chemotherapy. In our case, surgical excision was not possible, therefore the patient received two lines of chemotherapy followed by bone marrow allotransplantation, then a third line of chemotherapy with a complete metabolic response seen on PET/computed tomography (CT) follow-up 29 months later. A review of the literature has been performed. PMID:25698886

  7. Effects of age-related differences in femoral loading and bone mineral density on strains in the proximal femur during controlled walking

    PubMed Central

    Anderson, Dennis E.; Madigan, Michael L.

    2013-01-01

    Maintenance of healthy bone mineral density (BMD) is important for preventing fractures in older adults. Strains experienced by bone in vivo stimulate remodeling processes which can increase or decrease BMD. However, there has been little study of age differences in bone strains. This study examined the relative contributions of age-related differences in femoral loading and BMD to age-related differences in femoral strains during walking using gait analysis, static optimization, and finite element modeling. Strains in older adult models were similar or larger than in young adult models. Reduced BMD increased strains in a fairly uniform manner, while older adult loading increased strains in early stance but decreased strains in late stance. Peak ground reaction forces, hip joint contact forces, and hip flexor forces were lower in older adults in late stance phase, and this helped older adults maintain similar strains as young adults despite lower BMD. Because walking likely represents a “baseline” level of stimulus for bone remodeling processes, increased strains during walking in older adults might indicate the extent of age-related impairment in bone remodeling processes. Such a measure might be clinically useful if it could be accurately determined with age-appropriate patient-specific loading, geometry, and BMD. PMID:23185080

  8. Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice

    PubMed Central

    Halade, Ganesh V; Rahman, Md M; Williams, Paul J; Fernandes, Gabriel

    2010-01-01

    The inverse relationship between fat in bone marrow and bone mass in the skeleton of aging subjects is well-known. However, there is no precise therapy for the treatment of bone marrow adiposity. We investigated the ability of conjugated linoleic acid (CLA) and fish oil (FO), alone or in combination, to modulate bone loss using 12 months old C57Bl/6J mice fed 10% corn oil (CO) diet as control or supplemented with 0.5% CLA or 5% FO or 0.5% CLA+5% FO for 6 months. We found, CLA fed mice exhibited reduced body weight, body fat mass (BFM), and enhanced hind leg lean mass (HLLM) and bone mineral density (BMD) in different regions measured by DXA; however, associated with fatty liver and increased insulin resistance; whereas, FO fed mice exhibited enhanced BMD, improved insulin sensitivity, with no changes in BFM and HLLM. Interestingly, CLA+FO fed mice exhibited reduced body weight, BFM, PPARγ and cathepsin K expression in bone marrow with enhanced BMD and HLLM. Moreover, CLA+FO supplementation reduced liver hypertrophy and improved insulin sensitivity with remarkable attenuation of bone marrow adiposity, inflammation and oxidative stress in aging mice. Therefore, CLA with FO combination might be a novel dietary supplement to reduce fat mass and improve BMD. PMID:20656466

  9. Effects of cadmium, calcium, age and parity on bone mineral, density and strength in female rats

    SciTech Connect

    Hammond, B.F.

    1985-06-01

    Weanling female rats were fed diets containing one of three levels of calcium and one of four levels of cadmium in the drinking water. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppM Cd were smaller at birth than offspring of dams treated with 0 or 1 ppM Cd. Offspring of dams fed 5 or 10 ppM Cd or the 0.3% Ca diet had decreased weaning weight regardless of parity. Cadmium treatment had no effect on the plasma Ca or the Ca-P ratio. At Cd levels of 5 or 10 ppM the plasma P was increased. The 0.3% Ca diet depressed the plasma Ca and the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet. Parity did not affect plasma Ca but, after four pregnancies, plasma P was decreased. Plasma Ca of mature dams was higher than that of adolescent dams but plasma P was unaffected. Bone mineral, density and strength were decreased by the 0.3% Ca diet especially when Cd levels reached 10 ppM. Increasing dietary Ca above normal increased femur Ca of dams fed 1 ppM Cd but did not increase the Ca of the femur of dams given higher levels of Cd. After the first pregnancy, femur Ca of mature dams was greater than that of adolescent dams. After the fourth pregnancy, femurs of mature dams were less strong than those of adolescent dams; however, the density was the same. Increasing dietary Ca above 0.6% lessened the detrimental effects of 5 ppM Cd ingestion on bone density. Mature dams were less affected by the 0.3% Ca 10 ppM Cd treatment than were adolescent dams. 60 refs., 3 figs., 26 tabs.

  10. Bone Mass and Strength in School-Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study.

    PubMed

    Medina-Gomez, Carolina; Heppe, Denise Hm; Yin, Jia-Lian; Trajanoska, Katerina; Uitterlinden, André G; Beck, Thomas J; Jaddoe, Vincent Wv; Rivadeneira, Fernando

    2016-05-01

    Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school-age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole-body and hip scans were measured using the same densitometer (GE-Lunar iDXA) at a mean age of 6.2 years. Hip dual-energy X-ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole-body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre- and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American

  11. Association of advanced age with concentrations of uraemic toxins in CKD.

    PubMed

    Rroji, Merita; Eloot, Sunny; Dhondt, Annemie; Van Biesen, Wim; Glorieux, Griet; Neirynck, Nathalie; Vandennoortgate, Nele; Liabeuf, Sophie; Massy, Ziad; Vanholder, Raymond

    2016-02-01

    To our knowledge, there are no studies on advanced chronic kidney disease (CKD) analysing the impact of ageing on serum concentrations of uraemic toxins while adjusting for renal function. Knowledge of this feature, however, could influence prognostic assessment and therapeutic decision-making, e.g. about when to start dialysis or how intensive it should be. Indeed, the slowing down of metabolism with age may result in lower uraemic toxin concentrations, hence reducing their toxic effects. In this case, a later start of dialysis or less intensive dialysis may become justified in an already fragile population that might enjoy a better quality of life without a survival disadvantage with conservative treatment. We assessed the impact of advancing age on uraemic solute concentrations [blood, urea, nitrogen (BUN), uric acid, creatinine, asymmetric and symmetric dimethylarginine (ADMA and SDMA), β2-microglobulin and a large array of protein-bound solutes] by matching 126 maintenance haemodialysis patients subdivided into two age-groups, younger vs. older (using the median as cut-off: 72 years). Concentrations were compared after age stratification and were matched with patient and dialysis characteristics. In addition, 93 non-dialysed CKD patients (median as cut-off: 70 years), with a comparable average estimated glomerular filtration rate (eGFR) between younger and older age-groups, were analysed. In haemodialysis patients, carboxy-methyl-furanpropionic acid (CMPF) levels were markedly higher and BUN and uric acid borderline lower in the older age-group. All other solutes showed no difference. At multifactor analysis, the concentration of several uraemic toxins was associated with residual renal function and protein intake in the overall haemodialysis group and the younger group, but the association with most solutes, especially those protein-bound, was lost in the older age-group. No differences were found in non-dialysed CKD patients. It was concluded that in this

  12. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  13. Fracture Risk Assessment in Older Adults Using a Combination of Selected Quantitative Computed Tomography Bone Measures: A Subanalysis of the Age, Gene/Environment Susceptibility-Reykjavik Study

    PubMed Central

    Rianon, Nahid J.; Lang, Thomas F.; Siggeirsdottir, Kristin; Sigurdsson, Gunnar; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Jonsson, Brynjolfur Y.; Garcia, Melissa; Yu, Binbing; Kapadia, Asha S.; Taylor, Wendell C.; Selwyn, Beatrice J.; Gudnason, Vilmundur; Launer, Lenore J.; Harris, Tamara B.

    2016-01-01

    Bone mineral density (BMD) and geometric bone measures are individually associated with prevalent osteoporotic fractures. Whether an aggregate of these measures would better associate with fractures has not been examined. We examined relationships between self-reported fractures and selected bone measures acquired by quantitative computerized tomography (QCT), a composite bone score, and QCT-acquired dual-energy X-ray absorptiometry–like total femur BMD in 2110 men and 2682 women in the Age, Gene/Environment Susceptibility-Reykjavik Study. The combined bone score was generated by summing gender-specific Z-scores for 4 QCT measures: vertebral trabecular BMD, femur neck cortical thickness, femur neck trabecular BMD, and femur neck minimal cross-sectional area. Except for the latter measure, lower scores for QCT measures, singly and combined, showed positive (p < 0.05) associations with fractures. Results remained the same in stratified models for participants not taking bone-promoting medication. In women on bone-promoting medication, greater femur neck cortical thickness and trabecular BMD were significantly associated with fracture status. However, the association between fracture and combined bone score was not stronger than the associations between fracture and individual measures or total femur BMD. Thus, the selected measures did not all similarly associate with fracture status and did not appear to have an additive effect on fracture status. PMID:23562129

  14. Clinical relevance of radiologic examination of the skeleton and bone density measurements in osteoporosis of old age

    SciTech Connect

    Kuester, W.; Seidl, G.; Linkesch, W.; Kotscher, E.; Kovarik, J.; Willvonseder, R.; Kovarik, J.; Willvonseder, R.; Dorda, W.

    1981-10-01

    For the diagnosis of primary osteoporosis, various semiquantitative radiologic methods were compared in 149 unselected patients, aged over 50 years. Crush fracture syndrome (CFS), lumbar spine index (LSI), and Singh Index (SI) were assessed by three radiologists and after reevaluation, the intra- and interobserver errors were calculated. The reliability of the subjective grading was improved by joint and repeated reading of the radiographs. Additionally, the peripheral trabecular bone content was measured by photon absorption densitometry (PAD). To test the value of the various semiquantitative methods. LSI, Si, and PAD have been compared with sex-matching before and after separation into age in decades in CFS-positive and CFS-negative patients. In an attempt to differentiate osteoporotics and non-osteoporotics by CFS, our results indicate that CFS-positive and CFS-negative males cannot be separated by LSI, Si, and PAD, whereas in females these methods can discriminate irrespective of the age in decades. However, in age related groups, only SI can discriminate significantly between CFS-positive and CFS-negative females. Correlation of the semiquantitative methods, regardless of the diagnosis of a CFS, revealed a significant correlation-between SI and PAD, but no correlation between LSI and SI, and LSI and PAD, respectively.

  15. Regional effects of ovariectomy and cadmium on bone mineral in ribs from aged female beagles

    SciTech Connect

    Hurst, D.R. . Dept. of Zoology)

    1991-01-01

    The purpose of this study was to evaluate effects of estrogen depletion and cadmium (Cd) on bone calcium and to determine if these effects were localized in specific regions of ribs. Fourteen female beagles with {sup 45}Ca labeled skeletons were divided into four groups: sham controls (SO{minus}); ovariectomized (OV{minus}); shams exposed to Cd (SO+); ovariecomized exposed to Cd (OV+). Total Cd exposure period was 7 months, including 1 month by capsules and 6 months by drinking H{sub 2}O. Ribs were taken at necropsy from 12 of the 14 dogs, and each rib was quartered. Wet, dry, and ash weights, as well as total Ca and {sup 45}Ca content, were determined for each quarter. Analysis of ribs from control animals demonstrated that a given rib is heterogeneous in composition. One end appears to be less mineralized and more metabolically active than other regions. The OV{minus} and OV+ mid-rib regions had significantly lower dry and ash weights than SO{minus}. Total Ca contents of these same regions were also decreased in the OV{minus} and OV+. The only significant change in Ca/dry and Ca/ash was observed when comparing OV+ to SO{minus}. Analysis of treatment suggests that there are regional effects following ovariectomy increased the loss of bone mineral occurring as a result of ovariectomy. 30 refs., 1 fig.

  16. Stimulant medication effects on growth and bone age in children with attention-deficit/hyperactivity disorder: a prospective cohort study

    PubMed Central

    Bui, Quoc; Melzer, Elaine; Evans, Richard

    2016-01-01

    Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention-deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. Dexamphetamine or methylphenidate was titrated and continued when clinically indicated. Forty out of 73 patients, together with 22 controls, completed the study. There were no significant growth differences between the two groups at baseline. Despite slower growth on treatment [5.1 cm/year, 95% confidence interval (CI): 4.7–5.5, vs. 6.3 cm/year, 95% CI: 5.7–6.8, P=0.002; and 2.7 kg/year, 95% CI: 2.1–3.3, vs. 4.4 kg/year, 95% CI: 3.5–5.3, P=0.005], the patients showed no significant maturational delay (RUS score: 49 U/year, 95% CI: 44–55, vs. 55 U/year, 95% CI: 47–63, P=0.27). A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61±3.56–4.22±3.09 kg, P<0.001) and leptin (3.88±2.87–2.57±1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex). PMID:26544899

  17. Stimulant medication effects on growth and bone age in children with attention-deficit/hyperactivity disorder: a prospective cohort study.

    PubMed

    Poulton, Alison S; Bui, Quoc; Melzer, Elaine; Evans, Richard

    2016-03-01

    Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention-deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. Dexamphetamine or methylphenidate was titrated and continued when clinically indicated. Forty out of 73 patients, together with 22 controls, completed the study. There were no significant growth differences between the two groups at baseline. Despite slower growth on treatment [5.1 cm/year, 95% confidence interval (CI): 4.7-5.5, vs. 6.3 cm/year, 95% CI: 5.7-6.8, P=0.002; and 2.7 kg/year, 95% CI: 2.1-3.3, vs. 4.4 kg/year, 95% CI: 3.5-5.3, P=0.005], the patients showed no significant maturational delay (RUS score: 49 U/year, 95% CI: 44-55, vs. 55 U/year, 95% CI: 47-63, P=0.27). A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61±3.56-4.22±3.09 kg, P<0.001) and leptin (3.88±2.87-2.57±1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex). PMID:26544899

  18. Re-evaluation of Pleistocene and Holocene long bone robusticity trends with regards to age-at-death estimates and size standardization procedures.

    PubMed

    Friedl, Lukáš; Eisová, Stanislava; Holliday, Trenton W

    2016-08-01

    Long-term trends in robusticity of lower limb bones in the genus Homo through the Pleistocene until the present have been proposed, which have been interpreted as a consequence of decreasing levels of mobility and activity patterns, changes in lifestyle, and environmental factors. There has also long been evidence that skeletal strength increases over an individual's lifespan. This increase is caused by continuous bone remodeling that optimizes the structure of a bone to resist mechanical loadings and creates a balance between endosteal resorption and subperiosteal apposition. However, none of the previous studies of temporal trends in robusticity has considered both processes and analyzed how individual age-related robusticity might influence higher-level temporal trends. This paper therefore explores temporal trends in robusticity of lower limb long bones within the genus Homo and considers how individual ages-at-death can confound published evolutionary trends, given the fact that some aspects of relative bone strength tend to increase over individual lifespans. Cross-sectional diaphyseal properties of the midshaft and proximal femur and midshaft tibia of Pleistocene and early Holocene individuals, together with data on age-at-death are used to analyze changes in relative bone strength relative to individuals' ages and evolutionary time. The results show increasing bone strength in adulthood until the fourth decade and then a slight decrease, an observation that conforms to previously published results on recent human populations. However, no significant impact of age-at-death on the trends along an evolutionary trajectory has been detected. The evolutionary trends in femoral and tibial relative strength can be described as fluctuating, probably as a consequence of changing mobility patterns, environmentally and technologically influenced behaviors, and demographic processes. The differences between evolutionary trends published in several studies are explained

  19. Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity: Recent Advances and Future Perspectives

    PubMed Central

    Arbeev, Konstantin G.; Akushevich, Igor; Kulminski, Alexander M.; Ukraintseva, Svetlana V.; Yashin, Anatoliy I.

    2014-01-01

    Biodemography became one of the most innovative and fastest growing areas in demography. This progress is fueled by the growing variability and amount of relevant data available for analyses as well as by methodological developments allowing for addressing new research questions using new approaches that can better utilize the potential of these data. In this review paper, we summarize recent methodological advances in biodemography and their diverse practical applications. Three major topics are covered: (1) computational approaches to reconstruction of age patterns of incidence of geriatric diseases and other characteristics such as recovery rates at the population level using Medicare claims data; (2) methodological advances in genetic and genomic biodemography and applications to research on genetic determinants of longevity and health; and (3) biodemographic models for joint analyses of time-to-event data and longitudinal measurements of biomarkers collected in longitudinal studies on aging. We discuss how such data and methodology can be used in a comprehensive prediction model for joint analyses of incomplete datasets that take into account the wide spectrum of factors affecting health and mortality transitions including genetic factors and hidden mechanisms of aging-related changes in physiological variables in their dynamic connection with health and survival. PMID:25590047

  20. Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function

    PubMed Central

    Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C.; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J.; Januszyk, Michael; Maan, Zeshaan N.; Gurtner, Geoffrey C.

    2016-01-01

    Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing. PMID:26663425

  1. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products.

    PubMed

    Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

    2015-11-01

    The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow's feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation. PMID:26569300

  2. Successful aging: Advancing the science of physical independence in older adults.

    PubMed

    Anton, Stephen D; Woods, Adam J; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W; Carter, Christy S; Clark, David J; Cohen, Ronald A; Corbett, Duane B; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A; Fillingim, Roger B; Foster, Thomas C; Gundermann, David M; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M; Marsiske, Michael; Mankowski, Robert T; Mutchie, Heather L; Perri, Michael G; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J; Sibille, Kimberly T; Solberg, Laurence M; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

    2015-11-01

    The concept of 'successful aging' has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. A consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults. PMID:26462882

  3. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products

    PubMed Central

    Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

    2015-01-01

    The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow’s feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation. PMID:26569300

  4. In vitro simulation of pathological bone conditions to predict clinical outcome of bone tissue engineered materials

    NASA Astrophysics Data System (ADS)

    Nguyen, Duong Thuy Thi

    According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and non-unions. Compromised innate bone healing reactions of patients with bone diseases are exacerbated with protective bone therapy. Once these patients sustain a fracture, bone healing is a challenge, especially when fracture stabilization is unsuccessful. Traditional stabilizing screw and plate systems were designed with emphasis on bone mechanics rather than biology. Bone grafts are often used with fixation devices to provide skeletal continuity at the fracture gap. Current bone grafts include autologous bone tissue and donor bone tissue; however, the quality and quantity demanded by fragility fractures sustained by high-risk geriatric patients and patients with bone diseases are not met. Consequently, bone tissue engineering strategies are advancing towards functionalized bone substitutes to provide fracture reconstruction while effectively mediating bone healing in normal and diseased fracture environments. In order to target fragility fractures, fracture management strategies should be tailored to allow bone regeneration and fracture stabilization with bioactive bone substitutes designed for the pathological environment. The clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted

  5. Bone Quality in Paget's Disease of Bone.

    PubMed

    Singer, Frederick R

    2016-04-01

    Paget's disease of bone is produced by a localized increase in osteoclastic and osteoblastic activity which can progress slowly to involve an entire bone if untreated. A common feature is enlarged bones which are deformed, particularly in weight-bearing regions of the skeleton such as the lower extremity. Pathologic fractures may be a consequence, and nonunion of femoral fractures is not uncommon. Analyses of bone biopsies from patients with Paget's disease indicate that there is a lower, heterogeneous degree of bone mineralization and a younger tissue age than that found in control bone. Pagetic bone also has less resistance to plastic deformation and a straighter crack path than control bone. PMID:26943142

  6. Advances and Challenges in Immunotherapy for Solid Organ and Bone Marrow Transplantation

    PubMed Central

    McDonald-Hyman, Cameron; Turka, Laurence A.; Blazar, Bruce R.

    2015-01-01

    Although major advances have been made in hematopoietic stem cell transplantation (HSCT) and solid organ transplantation in the last 50 years, big challenges remain. This Review outlines the current immunological limitations for HSCT and solid organ transplantation, and discusses new immune-modulating therapies in clinical trials and under pre-clinical development that may allow these obstacles to be overcome. PMID:25810312

  7. Bone marrow derived stem cells in regenerative medicine as Advanced Therapy Medicinal Products

    PubMed Central

    Astori, Giuseppe; Soncin, Sabrina; Lo Cicero, Viviana; Siclari, Francesco; Sürder, Daniel; Turchetto, Lucia; Soldati, Gianni; Moccetti, Tiziano

    2010-01-01

    Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cellbased therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cellbased therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cellbased medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development. PMID:20589167

  8. Pregnancy and Birth Outcomes Among Primiparae at Very Advanced Maternal Age: At What Price?

    PubMed

    Ben-David, Alon; Glasser, Saralee; Schiff, Eyal; Zahav, Aliza Segev; Boyko, Valentina; Lerner-Geva, Liat

    2016-04-01

    Objectives In light of the potential physical and emotional costs to both woman and child, this study was conducted to assess pregnancy complications and birth outcomes in primiparae at very advanced maternal age (VAMA, aged ≥45) compared to younger primiparae. Methods Retrospective cohort study comparing 222 VAMA primiparae and a reference group of 222 primiparae aged 30-35, delivering at Sheba Medical Center from 2008 through 2013.Results VAMA primiparae were more likely than younger primiparae to be single, to have chronic health conditions, and higher rates of gestational diabetes mellitus (GDM), gestational-hypertension (GHTN) and preeclampsia-eclampsia. VAMA primiparae conceived mostly by oocyte donation. They were more likely to be hospitalized during pregnancy, to deliver preterm and by cesarean birth. Infants of VAMA primiparae were at greater risk for low birthweight and Neonatal Intensive Care Unit admission. There were no differences in outcomes between VAMA primiparae with or without preexisting chronic conditions, or between those aged 45-49 and ≥50. In multivariable analysis VAMA was an independent risk factor for GDM, GHTN and preeclamsia-eclampsia, with adjusted odds ratio of 2.38 (95 % CI 1.32, 4.29), 5.80 (95 % CI 2.66, 12.64) and 2.45 (95 % CI 1.03, 5.85); respectively. The effect of age disappeared in multiple pregnancies. Conclusions Primiparity at VAMA holds a significant risk for adverse pregnancy and birth outcomes. The absence of chronic medical conditions or the use of a young oocyte donor does not improve these outcomes. Multiple pregnancies hold additional risk and may diminish the effect of age. Primiparity at an earlier age should be encouraged. PMID:26686195

  9. Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy

    PubMed Central

    Schimke, Magdalena M.; Marozin, Sabrina; Lepperdinger, Günter

    2015-01-01

    Multipotential mesenchymal stromal cells (MSC) are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration. In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage, or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-vs.-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage. Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies? PMID:26696897

  10. Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy.

    PubMed

    Schimke, Magdalena M; Marozin, Sabrina; Lepperdinger, Günter

    2015-01-01

    Multipotential mesenchymal stromal cells (MSC) are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration. In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage, or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-vs.-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage. Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies? PMID:26696897

  11. Effect of dietary calcium on bone metabolism in young and aged female rats using a short-term in vivo model

    SciTech Connect

    Sinha, R.; Smith, J.C. Jr.; Soares, J.H. Jr.

    1988-10-01

    The use of high dietary calcium supplementation in the treatment of patients with osteoporosis is controversial. The present study examined the mechanisms underlying the effects of calcium supplementation by investigating the influence of dietary calcium on bone dynamics in young and aged rats. A 2 x 2 x 2 factorial design was utilized with 0.2% (low) or 1.0% (high) calcium, 2- or 24-m-old female Long-Evans rats that were implanted subcutaneously with demineralized (DB) and mineralized (MB) bone powder. The four groups of rats were fed each of the respective diets for 11 wk and then implanted with one number5 gelatin capsule containing 30 mg of DB and another containing 100 mg of MB powder. The animals were injected intraperitoneally with 0.1 microCi/g body weight with 45Ca 14 h before the end of experiment. The ectopic bone as well as the right femurs were harvested 14 d after the rats were implanted. Marker enzyme activities (alkaline-formation and acid-resorption phosphatase), 45Ca uptake and calcium content were measured in the implants and the distal epiphyses of the right femurs. Bone turnover was higher in the young rats than in the old animals, and high dietary calcium in the young animals increased bone formation, as indicated by alkaline phosphatase activity. Dietary calcium level did not affect ectopic bone formation or resorption in the aged rats. The results indicate that high dietary intake of calcium does not affect bone dynamics in aged female rats but does increase bone formation in young rats.

  12. Effects of cadmium, calcium, age and parity on bone mineral, density and strength in female rats

    SciTech Connect

    Hammond, B.F.

    1985-01-01

    Weanling female rats were fed diets containing one of three levels of Ca (0.3, 0.6, or 0.9%) and one of four levels of Cd (0, 1, 5, or 10 ppm) in the drinking water. One half of each group was fed first as adolescents (55 days) and the other half as mature (110 days) females. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppm Cd were smaller at birth than offspring of dams treated with 0 or 1 ppm Cd. After the fourth pregnancy, the decreased birth weight was evident only in offspring of dams treated with 10 ppm Cd. Offspring of dams fed 5 or 10 ppm Cd or the 0.3% Ca diet had decreased weaning weight regardless of parity. A 0.3% Ca diet superimposed upon a 5 or 10 ppm Cd intake decreased weaning weight of the male offspring after the first, but not the fourth, pregnancy with the offspring of adolescent dams affected more than those of mature dams. Offspring of dams fed the 0.9% Ca diet did not differ in weaning weight from the offspring of dams fed the 0.6% Ca diet. The 0.3% Ca diet depressed the plasma Ca and the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet.

  13. Study of an Unusual Advanced Glycation End-Product (AGE) Derived from Glyoxal Using Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Lopez-Clavijo, Andrea F.; Duque-Daza, Carlos A.; Romero Canelon, Isolda; Barrow, Mark P.; Kilgour, David; Rabbani, Naila; Thornalley, Paul J.; O'Connor, Peter B.

    2014-04-01

    Glycation is a post-translational modification (PTM) that affects the physiological properties of peptides and proteins. In particular, during hyperglycaemia, glycation by α-dicarbonyl compounds generate α-dicarbonyl-derived glycation products also called α-dicarbonyl-derived advanced glycation end products. Glycation by the α-dicarbonyl compound known as glyoxal was studied in model peptides by MS/MS using a Fourier transform ion cyclotron resonance mass spectrometer. An unusual type of glyoxal-derived AGE with a mass addition of 21.98436 Da is reported in peptides containing combinations of two arginine-two lysine, and one arginine-three lysine amino acid residues. Electron capture dissociation and collisionally activated dissociation results supported that the unusual glyoxal-derived AGE is formed at the guanidino group of arginine, and a possible structure is proposed to illustrate the 21.9843 Da mass addition.

  14. Effects of age, system experience, and navigation technique on driving with an advanced traveler information system.

    PubMed

    Dingus, T A; Hulse, M C; Mollenhauer, M A; Fleischman, R N; McGehee, D V; Manakkal, N

    1997-06-01

    This paper explores the effects of age, system experience, and navigation technique on driving, navigation performance, and safety for drivers who used TravTek, an Advanced Traveler Information System. The first two studies investigated various route guidance configurations on the road in a specially equipped instrumented vehicle with an experimenter present. The third was a naturalistic quasi-experimental field study that collected data unobtrusively from more than 1200 TravTek rental car drivers with no in-vehicle experimenter. The results suggest that with increased experience, drivers become familiar with the system and develop strategies for substantially more efficient and safer use. The results also showed that drivers over age 65 had difficulty driving and navigating concurrently. They compensated by driving slowly and more cautiously. Despite this increased caution, older drivers made more safety-related errors than did younger drivers. The results also showed that older drivers benefited substantially from a well-designed ATIS driver interface. PMID:9302887

  15. The Effects of Obesity on Murine Cortical Bone

    NASA Astrophysics Data System (ADS)

    Martin, Sophi

    This dissertation details the effects of obesity on the mechanical properties and structure of cortical bone. Obesity is associated with greater bone mineral content that might be expected to protect against fracture, which has been observed in adults. Paradoxically however, the incidence of bone fractures has been found to increase in overweight and obese children and adolescents. Femora from adolescent and adult mice fed a high-fat diet are investigated for changes in shape, tissue structure, as well as tissue-level and whole-bone mechanical properties. Results indicate increased bone size, reduced size-independent mechanical properties, but maintained size-dependent mechanical properties. Other changes in cortical bone response to obesity are observed with advancing age. This study indicates that bone quantity and bone quality play important compensatory roles in determining fracture risk, and that fracture risk may not be lessened for adults as previously thought.

  16. Decreased resting-state connections within the visuospatial attention-related network in advanced aging.

    PubMed

    Li, Yujie; Li, Chunlin; Wu, Qiong; Xu, Zhihan; Kurata, Tomoko; Ohno, Seiichiro; Kanazawa, Susumu; Abe, Koji; Wu, Jinglong

    2015-06-15

    Advanced aging is accompanied by a decline in visuospatial attention. Previous neuroimaging and electrophysiological studies have demonstrated dysfunction in specific brain areas related to visuospatial attention. However, it is still unclear how the functional connectivity between brain regions causes the decline of visuospatial attention. Here, we combined task and rest functional magnetic resonance imaging (fMRI) to investigate the age-dependent alterations of resting-state functional connectivity within the task-related network. Twenty-three young subjects and nineteen elderly subjects participated in this study, and a modified Posner paradigm was used to define the region of interest (ROI). Our results showed that a marked reduction in the number of connections occurred with age, but this effect was not uniform throughout the brain: while there was a significant loss of communication in the anterior portion of the brain and between the anterior and posterior cerebral cortices, communication in the posterior portion of the brain was preserved. Moreover, the older adults exhibited weakened resting-state functional connectivity between the supplementary motor area and left anterior insular cortex. These findings suggest that, the disrupted functional connectivity of the brain network for visuospatial attention that occurs during normal aging may underlie the decline in cognitive performance. PMID:25817360

  17. Factors Influencing the Prognosis of Octogenarians with Aortic Stenosis in the Advanced Aging Societies.

    PubMed

    Liang, Shuai; Yamaguchi, Kazuto; Yoshitomi, Hiroyuki; Ito, Saki; Nakashima, Ryuma; Sugamori, Takashi; Endo, Akihiro; Takahashi, Nobuyuki; Tanabe, Kazuaki

    2016-01-01

    Objective The recognition of clinical symptoms is critical to developing an effective therapeutic strategy for aortic valve stenosis (AS). Although AS is common, little is known about the factors influencing the natural history of AS patients who are 80 years of age older in advanced aging societies. We investigated the natural history and indications for valve procedures in AS patients of 80 years of age or older. Methods The medical records of 108 consecutive AS patients (moderate grade or higher) who are 80 years of age or older (mean age, 84.2±3.9 years; female, 65 patients) were reviewed to investigate their symptoms, the development of congestive heart failure, the incidence of referral for aortic valve replacement and death. The median duration of follow-up was 9 months (interquartile range, 2 to 25 months). Results The probability of remaining free of events (valve replacement and death) was 29±13% in all patients. There was no significant difference in the aortic valve area of the symptomatic and asymptomatic patients (0.85±0.28 cm(2) vs. 0.88±0.25 cm(2), p=0.59). The aortic valve (AV) velocity and AV area index were predictors of subsequent cardiac events (p<0.05). Conclusion The severity of AS was the only factor to affect the prognosis of AS patients who were 80 years old of age or older. It is necessary to frequently monitor the subjective symptoms of such patients and to objectively measure the AV area. PMID:27580533

  18. Biological Effects Induced by Specific Advanced Glycation End Products in the Reconstructed Skin Model of Aging.

    PubMed

    Pageon, Hervé; Zucchi, Hélène; Dai, Zhenyu; Sell, David R; Strauch, Christopher M; Monnier, Vincent M; Asselineau, Daniel

    2015-01-01

    Advanced glycation end products (AGEs) accumulate in the aging skin. To understand the biological effects of individual AGEs, skin reconstructed with collagen selectively enriched with N(ɛ)-(carboxymethyl)-lysine (CML), N(ɛ)-(carboxyethyl)-lysine (CEL), methylglyoxal hydroimidazolone (MG-H1), or pentosidine was studied. Immunohistochemistry revealed increased expression of α6 integrin at the dermal epidermal junction by CEL and CML (p<0.01). Laminin 5 was diminished by CEL and MG-H1 (p<0.05). Both CML and CEL induced a robust increase (p<0.01) in procollagen I. In the culture medium, IL-6, VEGF, and MMP1 secretion were significantly decreased (p<0.05) by MG-H1. While both CEL and CML decreased MMP3, only CEL decreased IL-6 and TIMP1, while CML stimulated TIMP1 synthesis significantly (p<0.05). mRNA expression studies using qPCR in the epidermis layer showed that CEL increased type 7 collagen (COL7A1), β1, and α6 integrin, while CML increased only COL7A1 (p<0.05). MG-H1-modified collagen had no effect. Importantly, in the dermis layer, MMP3 mRNA expression was increased by both CML and MG-H1. CML also significantly increased the mRNAs of MMP1, TIMP1, keratinocyte growth factor (KGF), IL-6, and monocyte chemoattractant protein 1 (MCP1) (p<0.05). Mixed effects were present in CEL-rich matrix. Minimally glycoxidized pentosidine-rich collagen suppressed most mRNAs of the genes studied (p<0.05) and decreased VEGF and increased MCP1 protein expression. Taken together, this model of the aging skin suggests that a combination of AGEs tends to counterbalance and thus minimizes the detrimental biological effects of individual AGEs. PMID:26309782

  19. Interactive 3D imaging technologies: application in advanced methods of jaw bone reconstruction using stem cells/pre-osteoblasts in oral surgery

    PubMed Central

    Wojtowicz, Andrzej; Perek, Jan; Popowski, Wojciech

    2014-01-01

    Cone beam computed tomography has created a specific revolution in maxillofacial imaging, facilitating the transition of diagnosis from 2D to 3D, and expanded the role of imaging from diagnosis to the possibility of actual planning. There are many varieties of cone beam computed tomography-related software available, from basic DICOM viewers to very advanced planning modules, such as InVivo Anatomage, and SimPlant (Materialise Dental). Through the use of these programs scans can be processed into a three-dimensional high-quality simulation which enables planning of the overall treatment. In this article methods of visualization are demonstrated and compared, in the example of 2 cases of reconstruction of advanced jaw bone defects using tissue engineering. Advanced imaging methods allow one to plan a miniinvasive treatment, including assessment of the bone defect's shape and localization, planning a surgical approach and individual graft preparation. PMID:25337171

  20. An online real-time DICOM web-based computer-aided diagnosis system for bone age assessment of children in a PACS environment

    NASA Astrophysics Data System (ADS)

    Ma, Kevin C.; Zhang, Aifeng; Moin, Paymann; Fleshman, Mariam; Vachon, Linda; Liu, Brent; Huang, H. K.

    2009-02-01

    Bone age assessment is a radiological procedure to evaluate a child's bone age based on his or her left-hand x-ray image. The current standard is to match patient's hand with Greulich & Pyle hand atlas, which is outdated by 50 years and only uses subjects from one region and one ethnicity. To improve bone age assessment accuracy for today's children, an automated race- and gender-specific bone age assessment (BAA) system has been developed in IPILab. 1390 normal left-hand x-ray images have been collected at Children's Hospital of Los Angeles (CHLA) to form the digital hand atlas (DHA). DHA includes both male and female children of ages one to eighteen and of four ethnic groups: African American, Asian American, Caucasian, and Hispanic. In order to apply DHA and BAA CAD into a clinical environment, a web-based BAA CAD system and graphical user interface (GUI) has been implemented in Women and Children's Hospital at Los Angeles County (WCH-LAC). A CAD server has been integrated in WCH's PACS environment, and a clinical validation workflow has been designed for radiologists, who compare CAD readings with G&P readings and determine which reading is more suited for a certain case. Readings are logged in database and analyzed to assess BAA CAD performance in a clinical setting. The result is a successful installation of web-based BAA CAD system in a clinical setting.

  1. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss

    PubMed Central

    Elo, Irma T.; Kohler, Iliana; Martikainen, Pekka

    2015-01-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive ageing, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971–2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35–49 and 50–72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25–29 at the time of birth. For example, maternal and paternal ages 40–49 were associated with mortality odds ratios (ORs)of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35–49. At ages 50–72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive ageing. PMID:24997641

  2. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.

    PubMed

    Myrskylä, Mikko; Elo, Irma T; Kohler, Iliana V; Martikainen, Pekka

    2014-10-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive aging, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971-2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35-49 and 50-72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25-29 at the time of birth. For example, maternal and paternal ages 40-49 were associated with mortality odds ratios (ORs) of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35-49. At ages 50-72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive aging. PMID:24997641

  3. Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

    PubMed Central

    Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

    2012-01-01

    Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

  4. Age- and sex-related changes in bone mass measured by neutron activation

    SciTech Connect

    Cohn, S.H.; Aloia, J.F.; Vaswani, A.N.; Zanzi, I.; Vartsky, D.; Ellis, K.J.

    1981-01-01

    Total-body calcium (TBCa) measurements have been employed in two basic types of studies. In the first type, serial measurements made on an individual patient are used to trace the time variation in body calcium. In the second type of study, the absolute total body calcium of an individual is determined and compared to a standard or predicted value in order to determine the deficit or excess of calcium. Generally, the standards are derived from data obtained from normal populations and grouped by the parameters of age and sex (mean value denoted TBCa/sub m/). In the study reported in this paper, the clinical usefulness of predicted calcium (TBCa/sub p/) is evaluated. The predicted value (TBCa/sub p/) for an individual is obtained with an algorithm utilizing values of sex and age, height and lean body mass (as derived from /sup 40/K measurement). The latter two components characterize skeletal size and body habitus, respectively. For the study, 133 white women and 71 white men ranging in age from 20 to 80 years were selected from a larger population. Individuals with evidence of metabolic calcium disorders or osteoporosis were excluded. Additionally, the women and men selected were first judged to have total body potassium levels in the normal range. For each age decade, the variance of TBCa values of these individuals, when expressed in terms of TBCa/sub p/, was significantly less than when expressed in terms of TBCa/sub m/. Thus, erroneous conclusions based on Ca deficit in osteoporosis could be drawn for individuals whose height and body size differ markedly from the average, as the variation of their TBCa values often exceeds the variation in the age and sex cohort. Data on a group of osteoporotic women were compared with the normal skeletal baseline values both in terms of the TBCa and the TBCa/sub p/ values.

  5. DNA aptamer raised against advanced glycation end products (AGEs) improves glycemic control and decreases adipocyte size in fructose-fed rats by suppressing AGE-RAGE axis.

    PubMed

    Ojima, A; Matsui, T; Nakamura, N; Higashimoto, Y; Ueda, S; Fukami, K; Okuda, S; Yamagishi, S

    2015-04-01

    Advanced glycation end products (AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE-oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose-fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements. PMID:25105541

  6. Magnetic poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering

    PubMed Central

    Gloria, A.; Russo, T.; D'Amora, U.; Zeppetelli, S.; D'Alessandro, T.; Sandri, M.; Bañobre-López, M.; Piñeiro-Redondo, Y.; Uhlarz, M.; Tampieri, A.; Rivas, J.; Herrmannsdörfer, T.; Dediu, V. A.; Ambrosio, L.; De Santis, R.

    2013-01-01

    In biomedicine, magnetic nanoparticles provide some attractive possibilities because they possess peculiar physical properties that permit their use in a wide range of applications. The concept of magnetic guidance basically spans from drug delivery and hyperthermia treatment of tumours, to tissue engineering, such as magneto-mechanical stimulation/activation of cell constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. Accordingly, the aim of this study was to develop fully biodegradable and magnetic nanocomposite substrates for bone tissue engineering by embedding iron-doped hydroxyapatite (FeHA) nanoparticles in a poly(ε-caprolactone) (PCL) matrix. X-ray diffraction analyses enabled the demonstration that the phase composition and crystallinity of the magnetic FeHA were not affected by the process used to develop the nanocomposite substrates. The mechanical characterization performed through small punch tests has evidenced that inclusion of 10 per cent by weight of FeHA would represent an effective reinforcement. The inclusion of nanoparticles also improves the hydrophilicity of the substrates as evidenced by the lower values of water contact angle in comparison with those of neat PCL. The results from magnetic measurements confirmed the superparamagnetic character of the nanocomposite substrates, indicated by a very low coercive field, a saturation magnetization strictly proportional to the FeHA content and a strong history dependence in temperature sweeps. Regarding the biological performances, confocal laser scanning microscopy and AlamarBlue assay have provided qualitative and quantitative information on human mesenchymal stem cell adhesion and viability/proliferation, respectively, whereas the obtained ALP/DNA values have shown the ability of the nanocomposite substrates to support osteogenic differentiation. PMID:23303218

  7. Magnetic poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering.

    PubMed

    Gloria, A; Russo, T; D'Amora, U; Zeppetelli, S; D'Alessandro, T; Sandri, M; Bañobre-López, M; Piñeiro-Redondo, Y; Uhlarz, M; Tampieri, A; Rivas, J; Herrmannsdörfer, T; Dediu, V A; Ambrosio, L; De Santis, R

    2013-03-01

    In biomedicine, magnetic nanoparticles provide some attractive possibilities because they possess peculiar physical properties that permit their use in a wide range of applications. The concept of magnetic guidance basically spans from drug delivery and hyperthermia treatment of tumours, to tissue engineering, such as magneto-mechanical stimulation/activation of cell constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. Accordingly, the aim of this study was to develop fully biodegradable and magnetic nanocomposite substrates for bone tissue engineering by embedding iron-doped hydroxyapatite (FeHA) nanoparticles in a poly(ε-caprolactone) (PCL) matrix. X-ray diffraction analyses enabled the demonstration that the phase composition and crystallinity of the magnetic FeHA were not affected by the process used to develop the nanocomposite substrates. The mechanical characterization performed through small punch tests has evidenced that inclusion of 10 per cent by weight of FeHA would represent an effective reinforcement. The inclusion of nanoparticles also improves the hydrophilicity of the substrates as evidenced by the lower values of water contact angle in comparison with those of neat PCL. The results from magnetic measurements confirmed the superparamagnetic character of the nanocomposite substrates, indicated by a very low coercive field, a saturation magnetization strictly proportional to the FeHA content and a strong history dependence in temperature sweeps. Regarding the biological performances, confocal laser scanning microscopy and AlamarBlue assay have provided qualitative and quantitative information on human mesenchymal stem cell adhesion and viability/proliferation, respectively, whereas the obtained ALP/DNA values have shown the ability of the nanocomposite substrates to support osteogenic differentiation. PMID:23303218

  8. Quality of advance care planning policy and practice in residential aged care facilities in Australia

    PubMed Central

    Silvester, William; Fullam, Rachael S; Parslow, Ruth A; Lewis, Virginia J; Sjanta, Rebekah; Jackson, Lynne; White, Vanessa; Gilchrist, Jane

    2013-01-01

    Objectives To assess existing advance care planning (ACP) practices in residential aged care facilities (RACFs) in Victoria, Australia before a systematic intervention; to assess RACF staff experience, understanding of and attitudes towards ACP. Design Surveys of participating organisations concerning ACP-related policies and procedures, review of existing ACP-related documentation, and pre-intervention survey of RACF staff covering their role, experiences and attitudes towards ACP-related procedures. Setting 19 selected RACFs in Victoria. Participants 12 aged care organisations (representing 19 RACFs) who provided existing ACP-related documentation for review, 12 RACFs who completed an organisational survey and 45 staff (from 19 RACFs) who completed a pre-intervention survey of knowledge, attitudes and behaviour. Results Findings suggested that some ACP-related practices were already occurring in RACFs; however, these activities were inconsistent and variable in quality. Six of the 12 responding RACFs had written policies and procedures for ACP; however, none of the ACP-related documents submitted covered all information required to meet ACP best practice. Surveyed staff had limited experience of ACP, and discrepancies between self reported comfort, and levels of knowledge and confidence to undertake ACP-related activities, indicated a need for training and ongoing organisational support. Conclusions Surveyed organisations â policies and procedures related to ACP were limited and the quality of existing documentation was poor. RACF staff had relatively limited experience in developing advance care plans with facility residents, although attitudes were positive. A systematic approach to the implementation of ACP in residential aged care settings is required to ensure best practice is implemented and sustained. PMID:24644755

  9. Quantification of Alterations in Cortical Bone Geometry Using Site Specificity Software in Mouse models of Aging and the Responses to Ovariectomy and Altered Loading

    PubMed Central

    Galea, Gabriel L.; Hannuna, Sion; Meakin, Lee B.; Delisser, Peter J.; Lanyon, Lance E.; Price, Joanna S.

    2015-01-01

    Investigations into the effect of (re)modeling stimuli on cortical bone in rodents normally rely on analysis of changes in bone mass and architecture at a narrow cross-sectional site. However, it is well established that the effects of axial loading produce site-specific changes throughout bones’ structure. Non-mechanical influences (e.g., hormones) can be additional to or oppose locally controlled adaptive responses and may have more generalized effects. Tools currently available to study site-specific cortical bone adaptation are limited. Here, we applied novel site specificity software to measure bone mass and architecture at each 1% site along the length of the mouse tibia from standard micro-computed tomography (μCT) images. Resulting measures are directly comparable to those obtained through μCT analysis (R2 > 0.96). Site Specificity analysis was used to compare a number of parameters in tibiae from young adult (19-week-old) versus aged (19-month-old) mice; ovariectomized and entire mice; limbs subjected to short periods of axial loading or disuse induced by sciatic neurectomy. Age was associated with uniformly reduced cortical thickness and site-specific decreases in cortical area most apparent in the proximal tibia. Mechanical loading site-specifically increased cortical area and thickness in the proximal tibia. Disuse uniformly decreased cortical thickness and decreased cortical area in the proximal tibia. Ovariectomy uniformly reduced cortical area without altering cortical thickness. Differences in polar moment of inertia between experimental groups were only observed in the proximal tibia. Aging and ovariectomy also altered eccentricity in the distal tibia. In summary, site specificity analysis provides a valuable tool for measuring changes in cortical bone mass and architecture along the entire length of a bone. Changes in the (re)modeling response determined at a single site may not reflect the response at different locations within the same

  10. Physical activity completed when young has residual bone benefits at 94 years of age: a within-subject controlled case study

    PubMed Central

    Warden, Stuart J.; Mantila Roosa, Sara M.

    2014-01-01

    Physical activity is recommended for skeletal health because bones adapt to mechanical loading. The young skeleton shows greatest plasticity to physical activity-related mechanical loads, but bones are most at risk of failure later in life. The discrepancy raises the question of whether the skeletal benefits of physical activity completed when young persist with aging. Here we present a unique case wherein the cortical bone benefit of physical activity completed over five decades earlier could be established within an individual aged in their tenth decade of life. Specifically, we compared bone properties at the midshaft humerus between the throwing and nonthrowing arms of a 94-year-old former Major League Baseball player who ceased throwing 55 years earlier. By performing analyses within-subject, the long-term skeletal benefit of physical activity completed when young could be assessed independent of inherited and systemic traits. Also, as the subject threw left-handed during his throwing career, but was right-hand dominant in all other activities throughout life, any lasting skeletal benefits in favor of the throwing arm could not be attributable to simple arm dominance. Analyses indicated that any cortical bone mass, area and thickness benefits of throwing-related physical activity completed when young were lost with aging, possibly due to accelerated intracortical remodeling. In contrast, the subject’s throwing (nondominant) arm had greater total cross-sectional area and estimated strength (polar moment of inertia) than in his dominant arm, despite muscle indices favoring the latter. These data indicate that physical activity completed when young can have lasting benefits on bone size and strength, independent of the maintenance of bone mass benefits. PMID:24879028

  11. Age-dependent changes in spontaneous frequency of micronucleated erythrocytes in bone marrow and DNA damage in peripheral blood of Swiss mice.

    PubMed

    Bhilwade, Hari N; Jayakumar, S; Chaubey, R C

    2014-08-01

    Age-dependent changes in chromosomal damage in bone marrow - a self-proliferating tissue - in the form of spontaneously occurring micronucleated erythrocytes, and DNA damage in peripheral blood were examined in male and female Swiss mice. In the erythrocyte population in the bone marrow, polychromatic (immature) erythrocytes showed a significant increase in the frequency of micronuclei as a function of age of the mice (1-20 months). The increase in micronucleus frequency was less in normochromatic (mature) erythrocytes. The female mice showed a higher frequency of micronuclei than the male mice in all the age groups examined. However, the female to male ratio of micronucleus frequencies in total erythrocytes as well as in polychromatic erythrocytes decreased with age. DNA damage, measured as tail moment in the single-cell gel electrophoresis in peripheral blood of different age groups of mice (1, 6, 12 and 18 months) showed a gradual increase with age. Female mice showed more DNA damage than 1-month and 18-month-old male mice. In conclusion, these results show that there is an accumulation of genetic damage in bone marrow and DNA damage in peripheral blood of mice during ageing, and that females show more alterations than males. PMID:25344168

  12. A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

  13. Image analysis of pubic bone for age estimation in a computed tomography sample.

    PubMed

    López-Alcaraz, Manuel; González, Pedro Manuel Garamendi; Aguilera, Inmaculada Alemán; López, Miguel Botella

    2015-03-01

    Radiology has demonstrated great utility for age estimation, but most of the studies are based on metrical and morphological methods in order to perform an identification profile. A simple image analysis-based method is presented, aimed to correlate the bony tissue ultrastructure with several variables obtained from the grey-level histogram (GLH) of computed tomography (CT) sagittal sections of the pubic symphysis surface and the pubic body, and relating them with age. The CT sample consisted of 169 hospital Digital Imaging and Communications in Medicine (DICOM) archives of known sex and age. The calculated multiple regression models showed a maximum R (2) of 0.533 for females and 0.726 for males, with a high intra- and inter-observer agreement. The method suggested is considered not only useful for performing an identification profile during virtopsy, but also for application in further studies in order to attach a quantitative correlation for tissue ultrastructure characteristics, without complex and expensive methods beyond image analysis. PMID:24986514

  14. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  15. Recent Demographic Developments in France: Relatively Low Mortality at Advanced Ages

    PubMed Central

    Prioux, France; Barbieri, Magali

    2013-01-01

    France had 65.3 million inhabitants as of 1 January 2012, including 1.9 million in the overseas départements. The population is slightly younger than that of the European Union as a whole. Population growth continues at the same rate, mainly through natural increase. There are now more African than European immigrants living in France. Fertility was practically stable in 2011 (2.01 children per woman), but the lifetime fertility of the 1971–1972 cohorts reached a historic low in metropolitan France (1.99 children per woman), nevertheless remaining among the highest in Europe. Abortion levels remained stable and rates among young people are no longer increasing. The marriage rate is falling and the divorce rate has stabilized (46.2 divorces per 100 marriages in 2011). The risk of divorce decreases with age, but has greatly increased among the under-70s over the last decade. Life expectancy at birth (78.4 years for men, 85.0 for women) has continued to increase at the same rate, mainly thanks to progress at advanced ages. Among European countries, France has the lowest mortality in the over-65 age group, but it ranks less well for premature mortality. PMID:24285939

  16. Immunoparesis and monoclonal gammopathy of undetermined significance are disassociated in advanced age.

    PubMed

    Cherry, Benjamin M; Costello, Rene; Zingone, Adriana; Burris, Jason; Korde, Neha; Manasanch, Elisabet; Kwok, Mary; Annunziata, Christina; Roschewski, Mark J; Engels, Eric A; Landgren, Ola

    2013-02-01

    Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of immune dysfunction predictive of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have reported increased prevalence of MGUS by age, but no study has examined the relationship between immunoparesis and abnormal FLC ratios in the elderly. We screened 453 older adults (median age, 80 years; range, 65-96) to characterize the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001), respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the youngest and oldest groups. Our observed disassociation between MGUS prevalence and impaired immunoglobulin production suggests that separate mechanisms are involved in the development of MGUS and immunoparesis in advanced age. These findings emphasize the need for molecularly defined methods to characterize myeloma precursor states and better predict progression to MM. PMID:23169485

  17. Inter-correlation of knowledge, attitude, and osteoporosis preventive behaviors in women around the age of peak bone mass

    PubMed Central

    2014-01-01

    Background As silent and preventable in nature, postmenopausal osteoporosis awareness should be raised among young women prior to an irreversible period of declining bone mass. We therefore decided to assess the inter-correlation of knowledge, attitude and osteoporosis preventive behaviors in women around the age of peak bone mass. Methods A cross-sectional study was conducted in 430 women aged 20–35 years. The participants’ knowledge, attitude and behaviors concerning osteoporosis prevention were assessed along with demographic data using a four-part questionnaire. The items in this questionnaire were established by extensive literature review, including the Guideline for Management of Osteoporosis of the Thai Osteoporosis Foundation (TOPF) 2010. The content was validated by experts in osteoporosis and reliability was obtained with a Cronbach’s alpha score of 0.83. Results The mean age of women in this study was 29.4 ± 4.6 years. Half of the participants (49.5%) had heard about osteoporosis, mostly from television (95.3%, n = 203/213) and the internet (72.8%, n = 155/213). Most women had certain knowledge (85.2%) and positive attitude towards osteoporosis (53.3%). Nevertheless, 80% of the studied population did not have appropriate osteoporosis behaviors. We found significant correlation between the level of attitudes and osteoporosis behaviors (adjusted odd ratio = 3.3 with 95% confidence interval of 1.9-5.7); attitude and educational level (adjusted odd ratio = 2.2 with 95% confidence interval of 1.4-3.4); and attitude and knowledge (adjusted odd ratio = 3.5 with 95% confidence interval of 1.8-6.8). Conclusion Despite having certain knowledge about osteoporosis, the young women did not seem to have appropriate osteoporosis preventive behaviors. Developing a right attitude towards osteoporosis may be a key determinant to improving health practices in order to prevent osteoporosis. PMID:24588970

  18. An artifacts removal post-processing for epiphyseal region-of-interest (EROI) localization in automated bone age assessment (BAA)

    PubMed Central

    2011-01-01

    Background Segmentation is the most crucial part in the computer-aided bone age assessment. A well-known type of segmentation performed in the system is adaptive segmentation. While providing better result than global thresholding method, the adaptive segmentation produces a lot of unwanted noise that could affect the latter process of epiphysis extraction. Methods A proposed method with anisotropic diffusion as pre-processing and a novel Bounded Area Elimination (BAE) post-processing algorithm to improve the algorithm of ossification site localization technique are designed with the intent of improving the adaptive segmentation result and the region-of interest (ROI) localization accuracy. Results The results are then evaluated by quantitative analysis and qualitative analysis using texture feature evaluation. The result indicates that the image homogeneity after anisotropic diffusion has improved averagely on each age group for 17.59%. Results of experiments showed that the smoothness has been improved averagely 35% after BAE algorithm and the improvement of ROI localization has improved for averagely 8.19%. The MSSIM has improved averagely 10.49% after performing the BAE algorithm on the adaptive segmented hand radiograph. Conclusions The result indicated that hand radiographs which have undergone anisotropic diffusion have greatly reduced the noise in the segmented image and the result as well indicated that the BAE algorithm proposed is capable of removing the artifacts generated in adaptive segmentation. PMID:21952080

  19. Bone age assessment in Hispanic children: digital hand atlas compared with the Greulich and Pyle (G&P) atlas

    NASA Astrophysics Data System (ADS)

    Fernandez, James Reza; Zhang, Aifeng; Vachon, Linda; Tsao, Sinchai

    2008-03-01

    Bone age assessment is most commonly performed with the use of the Greulich and Pyle (G&P) book atlas, which was developed in the 1950s. The population of theUnited States is not as homogenous as the Caucasian population in the Greulich and Pyle in the 1950s, especially in the Los Angeles, California area. A digital hand atlas (DHA) based on 1,390 hand images of children of different racial backgrounds (Caucasian, African American, Hispanic, and Asian) aged 0-18 years was collected from Children's Hospital Los Angeles. Statistical analysis discovered significant discrepancies exist between Hispanic and the G&P atlas standard. To validate the usage of DHA as a clinical standard, diagnostic radiologists performed reads on Hispanic pediatric hand and wrist computed radiography images using either the G&P pediatric radiographic atlas or the Children's Hospital Los Angeles Digital Hand Atlas (DHA) as reference. The order in which the atlas is used (G&P followed by DHA or vice versa) for each image was prepared before actual reading begins. Statistical analysis of the results was then performed to determine if a discrepancy exists between the two readings.

  20. Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

    PubMed

    Sroga, Grażyna E; Wu, Ping-Cheng; Vashishth, Deepak

    2015-01-01

    Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones. PMID:25629402

  1. Insulin-Like Growth Factor 1, Glycation and Bone Fragility: Implications for Fracture Resistance of Bone

    PubMed Central

    Sroga, Grażyna E.; Wu, Ping-Cheng; Vashishth, Deepak

    2015-01-01

    Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone