Increase In Bone Size Research Articles

Changes in bone density and structure of proximal humerus with aging in Chinese women

AimsThis study aimed to investigate age- and menopause-related differences in bone mineral density (BMD), bone structure and estimated bone strength at surgical neck of humerus in Chinese female sample. MethodsWe conducted a cross-sectional cohort study of 171 Chinese women. Bone mass, indices of geometric properties and estimated mechanical strength of the surgical neck were evaluated by quantitative computed tomography (QCT). Comparisons were performed across menstrual status categories. Age-related changes in QCT-derived bone parameters were calculated. ResultsThe age-related difference of BMD and cortical thickness was 40.25 % and 32.86 % between the age of 20 and 86 years. Progressive periosteal and endosteal expansion was associated linearly with age. Estimated mechanical strength indexes showed significant quadratic associations with age, with their peak occurred at the age of 46–55 years. The quartile of women with the greatest medullary diameter also had the lowest valve of BMD and cortical thickness and the greatest in skeletal width. Compared to premenopausal individuals, perimenopausal women were distinguished by lower cortical thickness (18.63 %) and BMD (20.05 %). The continued decrease in cortical thickness and BMD was noted after menopause. The medullary and periosteal diameter increased by 17.98 % and 9.34 % respectively in perimenopausal period, but not after menopause. The accelerated loss of the maximum and polar section modulus was observed in late postmenopausal women. ConclusionsThe increase in bone size only occurred during the menopause transition. Obvious loss of resistance to bending was in late postmenopausal period.

Cartilage thickness and bone shape variations as a function of sex, height, body mass, and age in young adult knees

The functional relationship between bone and cartilage is modulated by mechanical factors. Scarce data exist on the relationship between bone shape and the spatial distribution of cartilage thickness. The aim of the study was to characterise the coupled variation in knee bone morphology and cartilage thickness distributions in knees with healthy cartilage and investigate this relationship as a function of sex, height, body mass, and age. MR images of 51 knees from young adults (28.4 ± 4.1 years) were obtained from a previous study and used to train a statistical shape model of the femur, tibia, and patella and their cartilages. Five multiple linear regression models were fitted to characterise morphology as a function of sex, height, body mass, and age. A logistic regression classifier was fitted to characterise morphological differences between males and females, and tenfold cross-validation was performed to evaluate the models’ performance. Our results showed that cartilage thickness and its distribution were coupled to bone morphology. The first five shape modes captured over 90% of the variance and described coupled changes to the bone and spatial distribution of cartilage thickness. Mode 1 (size) was correlated to sex (p < 0.001) and height (p < 0.0001). Mode 2 (aspect ratio) was also correlated to sex (p = 0.006) and height (p = 0.017). Mode 4 (condylar depth) was correlated to sex only (p = 0.024). A logistic regression model trained on modes 1, 2, and 4 could classify sex with an accuracy of 92.2% (95% CI [81.1%, 97.8%]). No other modes were influenced by sex, height, body mass, or age. This study demonstrated the coupled relationship between bone and cartilage, showing that cartilage is thicker with increased bone size, diaphysis size, and decreased femoral skew. Our results show that sex and height influence bone shape and the spatial distribution of cartilage thickness in a healthy young adult population, but body mass and age do not.

Lack of periosteal apposition in the head and neck of femur after menopause in Chinese women with high risk for hip fractures - A cross-sectional study with QCT.

In elderly subjects and in particular in those with osteoporosis the evidence on age related volume changes of the hip is still very limited. Even less is known about bone changes of the femoral head. The aim of this study is to explore associations of bone size of the femoral head and neck with age in postmenopausal women with very high risk of hip fracture and to investigate associations of femoral head and neck bone mineral density. MIAF (medical image analysis framework)-Femur was used for the analysis of CT datasets from 319 females with acute hip fractures age 50 to 98. Integral BMD and volume of the head and neck were assessed. The femoral head was divided into four quadrants to address differential vBMD and volume responses of its superior, inferior, posterior and anterior parts. Areal BMD (aBMD) of femoral neck was also obtained. In this population of postmenopausal women we did not observe age-related changes in bone volume of the femoral head or neck between ages 50 and 98years. Integral vBMD in the head in the 90-98year group was 48.0mg/cm3 lower than that in 50-59year group, which accounts for nearly 30% decrease in vBMD with 40years increase. Age-related vBMD changes in the head quadrants were similar to that in total. With age, the trend line correlation coefficients for vBMD in quadrants were relatively small, but significant (p<0.001) for all. The femoral head integral vBMD correlates well with neck vBMD and FN aBMD. FN aBMD explained 45% of head integral vBMD variance (p<0.0001). Elderly women had relative preservation of femoral head and neck bone volume from 50yrs. over four decades but markedly lower integral vBMD of proximal femur. The findings of our study call in question about the concept of bone expansion with aging even in elderly age.

PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology.

Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1707-1715, 2017.

Expression of Caveolin-1 in Periodontal Tissue and Its Role in Osteoblastic and Cementoblastic Differentiation In Vitro.

It has been previously reported that caveolin-1 (Cav-1) knockout mice exhibit increased bone size and stiffness. However, the expression and role of Cav-1 on periodontal tissue is poorly understood. The aim of this study was to investigate the immunohistochemical expression of Cav-1 in the mouse periodontium and explore the role of Cav-1 on osteoblastic and cementoblastic differentiation in human periodontal ligament cells (hPDLCs), cementoblasts, and osteoblasts. To reveal the molecular mechanisms of Cav-1 activity, associated signaling pathways were also examined. Immunolocalization of Cav-1 was studied in mice periodontal tissue. Differentiation was evaluated by ALP activity, alizarin red S staining, and RT-PCR for marker genes. Signal transduction was analyzed using Western blotting and confocal microscopy. Cav-1 expression was observed in hPDLCs, cementoblasts, and osteoblasts of the periodontium both in vivo and in vitro. Inhibition of Cav-1 expression by methyl-β-cyclodextrin (MβCD) and knockdown of Cav-1 by siRNA promoted osteoblastic and cementoblastic differentiation by increasing ALP activity, calcium nodule formation, and mRNA expression of differentiation markers in hPDLCs, cementoblasts, and osteoblasts. Osteogenic medium-induced BMP-2 and BMP-7 expression, and phosphorylation of Smad1/5/8 were enhanced by MβCD and siRNA knockdown of Cav-1, which was reversed by BMP inhibitor noggin. MβCD and Cav-1 siRNA knockdown increased OM-induced AMPK, Akt, GSK3β, and CREB phosphorylation, which were reversed by Ara-A, a specific AMPK inhibitor. Moreover, OM-induced activation of p38, ERK, JNK, and NF-κB was enhanced by Cav-1 inhibition. This study demonstrates, for the first time, that Cav-1 is expressed in developing periodontal tissue and in vitro in periodontal-related cells. Cav-1 inhibition positively regulates osteoblastic differentiation in hPDLCs, cementoblasts, and osteoblasts via BMP, AMPK, MAPK, and NF-κB pathway. Thus, Cav-1 inhibition may be a novel molecular target for therapeutic approaches in periodontitis or osteolytic disease.

Reduction of trabecular and cortical volumetric bone mineral density at the proximal femur in patients with acromegaly.

Data on dual energy absorptiometry (DXA)-measured bone mineral density (BMD) at the level of the total hip (TH) and femoral neck (FN) in patients with acromegaly (ACRO) are conflicting. Increase in bone size associated with ACRO may limit the reliability of DXA. Our objective is to evaluate trabecular and cortical volumetric BMD (vBMD) across the proximal femur in ACRO patients. Cross sectional study in a clinical research center. Thirty-five ACRO patients (19 males; mean age, 48±7 years; BMI, 27.5±4.4 kg/m(2); 17 with active disease) and 35 age, gender, and BMI-matched controls. vBMD was assessed by quantitative computed tomography at the level of the TH, FN, trochanter (TR), and intertrochanteric (IT). Trabecular vBMD was lower in both total and active ACRO as compared with controls (P<0.01). Cortical vBMD was lower in ACRO patients (active and controlled) vs controls at both TH and TR sites (P<0.05). These findings were confirmed when only eugonadal patients were analyzed. Both total cross sectional area (CSA) and average cortical thickness (ACT) were greater in ACRO patients vs controls (P<0.05). An inverse association between disease duration and trabecular vBMD at TH (r=-0.42, P=0.023) and IT (r=-0.41, P=0.026) was also found. Both cortical and trabecular vBMD are reduced at the proximal femur in ACRO patients, regardless of gender, gonadal status, and disease activity. Disease duration is negatively associated with trabecular vBMD at the TH and IT.

Paradoxical effects of partial leptin deficiency on bone in growing female mice.

Morbidly obese, leptin-deficient ob/ob mice display low bone mass, mild osteoclast-rich osteopetrosis, and increased bone marrow adiposity. While partial leptin deficiency results in increased weight, the skeletal manifestations of partial leptin deficiency are less well defined. We therefore analyzed femora and lumbar vertebrae in growing (7-week-old) female C57BL/6 wildtype (WT) mice, partial leptin-deficient ob/+ mice, and leptin-deficient ob/ob mice. The bones were evaluated by dual energy absorptiometry, microcomputed tomography and histomorphometry. As expected, ob/+ mice were heavier, had more white adipose tissue, and lower serum leptin than WT mice, but were lighter and had less white adipose tissue than ob/ob mice. With a few exceptions, cancellous bone architecture, cell (osteoblast, osteoclast, and adipocyte), and dynamic measurements did not differ between WT and ob/+ mice. In contrast, compared to WT and ob/+ mice, ob/ob mice had lower cancellous bone volume fraction, and higher bone marrow adiposity in the femur metaphysis, and higher cancellous bone volume fraction in lumbar vertebra. Paradoxically, ob/+ mice had greater femoral bone volume than either WT or ob/ob mice. There was a positive correlation between body weight and femur volume in all three genotypes. However, the positive effect of weight on bone occurred with lower body weight in leptin-producing mice. The paradoxical differences in bone size among WT, ob/+, and ob/ob mice may be explained if leptin, in addition to stimulating bone growth and cancellous bone turnover, acts to lower the set-point at which increased body weight leads to a commensurate increase in bone size.

Calcium and Vitamin D Metabolism in Children in Developing Countries

Low dietary calcium intakes and poor vitamin D status are common findings in children living in developing countries. Despite many of the countries lying within the tropics and subtropics, overcrowding, atmospheric pollution, a lack of vitamin D-fortified foods, and social customs that limit skin exposure to sunlight are major factors in the development of vitamin D deficiency. Low dietary calcium intakes are typically observed as a consequence of a diet limited in dairy products and high in phytates and oxalates which reduce calcium bioavailability. Calcium intakes of many children are a third to a half of the recommended intakes for children living in developed countries, yet the consequences of these low intakes are poorly understood as there is limited research in this area. It appears that the body adapts very adequately to these low intakes through reducing renal calcium excretion and increasing fractional intestinal absorption. However, severe deficiencies of either calcium or vitamin D can result in nutritional rickets, and low dietary calcium intakes in association with vitamin D insufficiency act synergistically to exacerbate the development of rickets. Calcium supplementation in children from developing countries slightly increases bone mass, but the benefit is usually lost on withdrawal of the supplement. It is suggested that the major effect of calcium supplementation is on reducing the bone remodelling space rather than structurally increasing bone size or volumetric bone density. Limited evidence from one study raises concerns about the use of calcium supplements in children on habitually low calcium intakes as the previously supplemented group went through puberty earlier and had a final height several centimetres shorter than the controls.

Acute bone response to whole body vibration in pre-pubertal boys

Introduction and Aim of study Improvements in bone strength and increased bone size, density and formation as a result of whole body vibration (WBV) have been shown in animal models. Observations over a period of months in postmenopausal women1-3, young women with low bone mass4 and children with disabling conditions5, have shown that up to 10 minutes a day of WBV can significantly increase bone mass. Data regarding the effects of WBV in paediatric populations is limited. It is unclear how quickly the growing skeleton responds to additional externally–applied mechanical stimuli. The aim of this study was to determine the acute time course and magnitude of bone’s response to WBV in healthy pre-pubertal boys.

The relationships between femoral cortex geometry and tissue mechanical properties

Bone tissue and geometry are constantly modified through modeling and remodeling at the periosteal, endosteal and intracortical envelopes. Results from several studies indicate that femoral bone geometry is a predictor of whole bone strength (e.g. femoral neck strength), however, it is not known whether there is a relationship between bone structural and material properties. Bone geometry can be determined from parameters based on plane X-ray radiogrammetry which are used to evaluate femoral bone quality for implant success. If there is a relationship between these parameters and tissue mechanical properties, this would have implications in the interpretation of such parameters for assessment of fracture risk and in further understanding of bone biology. Following measurement of radiogrammetric parameters from antero-posterior and medio-lateral X-rays (cortical thickness, bone diameter, bone area, moment of inertia, cortical index, Singh index), human femurs were machined into standard test specimens for assessment of tensile fracture toughness (GIc) of the tissue. Results indicated that tensile fracture toughness generally increased with increasing bone size. We also found that fracture toughness of the tissue was significantly related to radiogrammetric indices and that some of these indices explained a greater variability in toughness than porosity, age or gender.

Femoral Neck Bone Strength Estimated by Hip Structural Analysis (HSA) in Swedish Caucasians Aged 6–90 Years

Dual-energy X-ray absorptiometry hip scans of 1,760 population-based Caucasians, 599 girls and 642 boys aged 6-19 years and 270 women and 249 men aged 20-90 years, were analyzed with the hip structural analysis (HSA) software to present age- and sex-specific normative HSA data of the femoral neck (FN). Measured traits included bone mineral density (BMD), cross-sectional area (CSA), section modulus (Z), periosteal diameter (PD), endosteal diameter (ED), cortical thickness (CT), and cross-sectional moment of inertia (CSMI). When plotting the measured traits versus age, the curves increased with higher ages until statistically significant break points were reached, for all traits at age 17 in girls and age 19 in boys. After the break points, PD and ED increased with higher ages but, as ED increased more than PD, BMD and CT decreased significantly with higher ages. The decline in BMD was counteracted by the increase in bone size so that there was only a nonstatistically significant decrease in bone strength, estimated as Z and CSMI, from break point to age 90. The partial preservation of bone strength was more obvious in men than in women as the decline in BMD was higher in women than in men, while the expansion in PD was larger in men than in women. The sex difference in the normative FN bone strength data seems to be related to sex discrepancies in the development of both bone mass and geometrical parameters during both growth and adulthood.

Knochendichtemessung am wachsenden Skelett und klinische Konsequenzen

The measurement of bone mineral density (BMD) was established to judge the fracture risk in an individual. The most commonly used densitometric technique DXA is a two-dimensional method and reports BMD (bone mass/projection area), which increases during growth. Bone mineral density (in g/cm(3)), however, is almost stable and does not change with age or height. To analyze the data special pediatric references including data on age, sex and ethnicity are necessary as well as correction for height. Bone forms a unit with muscle. Bone responds to mechanical loading with increase in bone size and therefore adapts to the biomechanical needs. Therefore, interpretation of bone development data requires data on muscle development.The indication for bone mineral density measurement and result reporting should be made by and together with a pediatric specialist. The diagnosis of osteoporosis should not be made based solely on densitometric measurements. History of low trauma fracture is an important aspect for the definition. Besides DXA there exist further methods with advantages and disadvantages.

Relationship of testosterone and osteocalcin levels during growth

Recent studies in mice have demonstrated that osteocalcin (OCN) regulates testosterone (T) production in males but not in females. We hypothesized that this novel bone-testis axis may be most relevant during rapid skeletal growth to help maximize bone size. Thus we measured serum T, total and undercarboxylated (UC) OCN, and periosteal circumference at the radius in 56 boys (bone age 4 to 20 years). T was correlated with OCN (bone-age-adjusted r = 0.30, p = .024), with a similar trend for UC OCN. T began to increase in the boys at bone age 11 years, and OCN peaked at bone age 14 years. Thus we divided the boys into three groups: 4 to 10 years (n = 16), 11 to 14 years (n = 18), and 15 to 20 years (n = 22). In boys of bone age 11 to 14 years (but not the other two groups), OCN was correlated with T (r = 0.57, p = .013), with a similar trend for UC OCN; T, in turn, was correlated with periosteal circumference (r = 0.75, p < .001). Collectively, these findings support the recent observations in mice of a novel bone-testis axis. Moreover, our data suggest that in human males, this axis may be most relevant during rapid skeletal growth, when T levels are rising under the influence of the hypothalamic-pituitary axis and OCN is increasing due to skeletal growth. During this phase, OCN may further stimulate testicular T production, which, in turn, contributes to an increase in bone size.

Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children

Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired.We recruited 530 children at 6years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany).Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=−14.6mg/mm3 per sd, p=0.003; β=−7.7mg/mm3 per sd, p=0.02 respectively).These results suggest that fat mass is negatively associated with volumetric bone density at 6years old, independent of lean mass, despite positive associations with bone size.This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.

The mechanism for consolidation of bone mass in young men and women: A high resolution quantitative computed tomography study

The period between the end of linear growth and peak bone mass has been referred to as ‘consolidation’. We have found that in men and women peak bone mass at the radius and lumbar spine occurs in the middle of the third decade. The aim of this study was to better understand the changes in the bone compartments of the radius using high resolution peripheral quantitative computed tomography (HR-pQCT) and to relate these changes to bone turnover markers. We studied 113 healthy male and female volunteers ages 16–18 and 30–32.Wemeasured spine and hip BMD with DXA, and examined the distal radius with HR-pQCT (Xtreme CT, Scanco Medical). We analysed the HR-pQCT images with the standard software and also with extended cortical bone measures software. We also measured serum βCTX and PINP. Spine BMDwas higher at ages 30–32 than at ages 16–18 inmen andwomen. Hip BMDwas similar in both age groups. Radius cortical BMDwas higher at ages 30–32 than at ages 16–18 in men and women, due to lower porosity and higher tissue mineral density. Trabecular bone volume, BMD, number, thickness and separation did not differ between age groups. Cortical perimeter, endosteal perimeter and trabecular area were greater at ages 30–32 than at ages 16–18 inmen, but not inwomen. Serum βCTX and PINPwere lower at ages 30–32 than at ages 16–18 in men and women. These analyses demonstrate that cortical consolidation is due to an increase in mineralisation of bone tissue and a decrease in porosity. This consolidation is probably due to the decrease in bone turnover between the end of growth and peak bone mass. Also, there is evidence for periosteal apposition and endosteal resorption with increase in bone size in men. The trabecular compartment does not contribute to consolidation, and seems to have reached its mature state by the end of growth.

Discordance between cortical and trabecular bone phenotype highlights the role of local versus circulating IGF-1 in the SOCS2 null mouse

Event Abstract Back to Event Discordance between cortical and trabecular bone phenotype highlights the role of local versus circulating IGF-1 in the SOCS2 null mouse R Dobie1*, C Huesa1, RJ Van'T Hof2, VE Macrae1, SF Ahmed3 and C Farquharson1 1 University of Edinburgh, Roslin Institute & R(D)SVS, United Kingdom 2 University of Edinburgh, Centre for Molecular Medicine, United Kingdom 3 University of Glasgow, Bone and Endocrine Research Group, United Kingdom Suppressor of Cytokine Signalling 2 (SOCS2) tightly regulates postnatal growth through its actions on the GH/IGF-1 pathway. SOCS2 knockout mice do not have raised circulating IGF-1 and are characterised by enhanced body size and bone length. However the trabecular architecture and cortical geometry of the bones have yet to be fully investigated. Further to this, the bone mechanical properties remain undefined. In order to better appreciate the role of SOCS2 in juvenile and adult male and female mice, we have conducted an in depth analysis of the bone phenotype. {BR}Micro-CT was carried out on the tibia of wild-type (WT) and SOCS2 knockout (KO) mice, at 6-weeks (juvenile) and 4-months (adult) of age. Analysis enabled detailed comparisons to be made between the trabecular and cortical macroarchitecture, and allowed for the calculation of the mineral density of the bone tissue. 3-point-bending was also completed to investigate the mechanical properties. {BR}A significant increase in body weight was observed in all KO mice (P<0.05). All KO mice had increased trabecular BV/TV compared to their age and sex matched WT controls which is a likely consequence of increased trabecular thickness (P<0.05). All KO mice had increased tibial periosteal surface area (P<0.05), however the cortex was thicker only in juvenile and adult KO male mice. The thicker cortex of the male KO mice tibia was associated with increased work to failure and maximum load. At 6 weeks of age there was no difference in the mineral density of the bone tissue in either gender, however at 4 months both male and female KO mice had a significant decrease of mineral density in the cortical bone (P<0.05).{BR}The increased bone size and mass are consistent with the known anabolic effects of local, skeletal, IGF-1 and these effects are age and sex specific. The fall in mineral density of cortical bone reflects the importance of circulating IGF-1 on cortical bone development. The SOCS2 KO mouse represents a valid model for studying the effects of GH and IGF-1 on bone. Keywords: Bones, Bone Research Conference: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011. Presentation Type: Oral Topic: Abstracts Citation: Dobie R, Huesa C, Van'T Hof R, Macrae V, Ahmed S and Farquharson C (2011). Discordance between cortical and trabecular bone phenotype highlights the role of local versus circulating IGF-1 in the SOCS2 null mouse. Front. Endocrinol. Conference Abstract: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society. doi: 10.3389/conf.fendo.2011.02.00015 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2011; Published Online: 30 Sep 2011. * Correspondence: Mr. R Dobie, University of Edinburgh, Roslin Institute & R(D)SVS, United Kingdom, ross.dobie@roslin.ed.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers R Dobie C Huesa RJ Van'T Hof VE Macrae SF Ahmed C Farquharson Google R Dobie C Huesa RJ Van'T Hof VE Macrae SF Ahmed C Farquharson Google Scholar R Dobie C Huesa RJ Van'T Hof VE Macrae SF Ahmed C Farquharson PubMed R Dobie C Huesa RJ Van'T Hof VE Macrae SF Ahmed C Farquharson Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice

SummaryDiabetic obesity is associated with increased fracture risk in adults and adolescents. We find in both adolescent and adult mice dramatically inferior mechanical properties and structural quality of cortical bone, in agreement with the human fracture data, although some aspects of the response to obesity appear to differ by age.IntroductionThe association of obesity with bone is complex and varies with age. Diabetic obese adolescents and adult humans have increased fracture risk. Prior studies have shown reduced mechanical properties as a result of high-fat diet (HFD) but do not fully address size-independent mechanical properties or structural quality, which are important to understand material behavior.MethodsCortical bone from femurs and tibiae from two age groups of C57BL/6 mice fed either HFD or low-fat diet (LFD) were evaluated for structural and bone turnover changes (SEM and histomorphometry) and tested for bending strength, bending stiffness, and fracture toughness. Leptin, IGF-I, and non-enzymatic glycation measurements were also collected.ResultsIn both young and adult mice fed on HFD, femoral strength, stiffness, and toughness are all dramatically lower than controls. Inferior lamellar and osteocyte alignment also point to reduced structural quality in both age groups. Bone size was largely unaffected by HFD, although there was a shift from increasing bone size in obese adolescents to decreasing in adults. IGF-I levels were lower in young obese mice only.ConclusionsWhile the response to obesity of murine cortical bone mass, bone formation, and hormonal changes appear to differ by age, the bone mechanical properties for young and adult groups are similar. In agreement with human fracture trends, adult mice may be similarly susceptible to bone fracture to the young group, although cortical bone in the two age groups responds to diabetic obesity differently.

Reduced size-independent mechanical properties of cortical bone in high-fat diet-induced obesity

Overweight and obesity are rapidly expanding health problems in children and adolescents. 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. Prior studies have shown some reduced mechanical properties as a result of high-fat diet (HFD) but do not fully address size-independent measures of mechanical properties, which are important to understand material behavior. To clarify the effects of HFD on the mechanical properties and microstructure of bone, femora from C57BL/6 mice fed either a HFD or standard laboratory chow (Chow) were evaluated for structural changes and tested for bending strength, bending stiffness and fracture toughness. Here, we find that in young, obese, high-fat fed mice, all geometric parameters of the femoral bone, except length, are increased, but strength, bending stiffness, and fracture toughness are all reduced. This increased bone size and reduced size-independent mechanical properties suggests that obesity leads to a general reduction in bone quality despite an increase in bone quantity; yield and maximum loads, however, remained unchanged, suggesting compensatory mechanisms. We conclude that diet-induced obesity increases bone size and reduces size-independent mechanical properties of cortical bone in mice. This study indicates that bone quantity and bone quality play important compensatory roles in determining fracture risk.

Chronic Recurrent Multifocal Osteomyelitis (CRMO): four cases treated with aminobisphosphonate (pamidronate)

CRMO is an autoinflammatory disease of children and young adults, characterized by the insidious onset of local pain and swelling in affected bone and fever. The bone lesions are radiologically characterized as multiple luciens surrounded by defined zones of patchy but dense sclerosis, cortical tickening from periosteal new bone formation, and increased bone size with different bones involved. Diagnosis is based upon laboratory tests (elevated levels of CRP/ESR), bone scintigraphy and MRI findings and is proved by open bone biopsy. Recently bisphosphonate therapy, and particulary i.v. pamidronate, has been proposed as treatment for patients both CRMO who do not responder to NSAIDs therapy. We report 4 cases of children affected by CRMO treated with a therapeutic cycle of aminobisphosphonate (pamidronate). In all pts. the diagnosis of CRMO was confirmed by bone scintigraphy, MRI and open bone biopsy. Pt.1. 12-years-old age (disease onset 10 yrs) presented with pain and swelling of right ankle, hip, knee and breastbone; CRP 2.4 mg/dl, ESR 100 mm/h. CRMO of right distal tibial epiphysis, right peroneal malleulus, breastbone and right hip. Pt.2. 5-years-old age presented with post-traumatic back pain in the past month and pathologic fracture of three thoracic vertebrae; normal values of CRP and ESR. CRMO of right iliac wing and thoracic spine (T8-T9-T10). Pt.3. 8-years-old age presented lumbar pain and swelling in the past month associated with antalgic scoliosis; CRP < 0.5 mg/dl, ESR 40 mm/h. CRMO of left distal tibial epiphysis, thoracic spine (T7–T8), right iliac wing. Pt.4 17-years-old age (disease onset 11 yrs) presented with post- traumatic pain and swelling of right hip and heel; CRP 1.6 mg/dl, ESR 29 mm/h. CRMO of bilateral distal tibial epiphysis, left calcaneus and neck of right femur. All 4 pts. were treated with 3 infusions of pamidronate 0.5–1.3 mg/kg/day in 250 ml of saline solution i.v. infusion at day 1,3,5 and then monthly. Severe adverse reaction was not found except for low-grade fever and lassitude on the day following administration. In all pts a remarkable improvement of painful symptoms was quikly achieved. MRI performed 1–3 months after treatment showed an important reduction of osteolytic, sclerotic and reactive bone lesions, and normalization of inflammatory values was observed. Our experience suggests that pamidronate maybe an efficacious alternative to conventional treatment in CRMO.

The ovariectomized, mature rat model of postmenopausal osteoporosis: An assessment of the bone sparing effects of curcumin

Identification of natural health products that might benefit skeletal health could reduce the negative impact of osteoporotic bone fractures upon society. The objectives of this study were to evaluate an animal model of postmenopausal osteoporosis and to search for evidence that curcumin reduces bone mineral losses in a dose-dependent manner when endogenous estrogen levels are reduced. Bone mineral density was measured at the spine, femur and whole body before and at 2, 4 and 6 months after ovariectomy in each of 40 mature rats. Serum osteocalcin and C-telopeptide were measured as indicators of bone formation and resorption rates. Femoral compressive strength was measured at 6 months. Ovariectomy alone resulted in loss of mineral from the spine (p<0.005) and an increase in osteocalcin levels (p<0.05). At the same time, there was an increase in energy to fracture (p<0.01) due to an increased bone size. When ovariectomized animals were given etidronate there was no loss of mineral from the spine, the size of the femur increased (p<0.005), C-telopeptide levels were reduced (p<0.001) and femoral compressive strength increased (p<0.025). Administration of curcumin to ovariectomized animals resulted in changes that were intermediate between those produced by etidronate and by ovariectomy alone. The increase in femur size produced by the highest dose of curcumin was statistically significant (p< 0.01) and curcumin administration resulted in a significant, dose dependent, increase in energy to fracture. Curcumin produces beneficial changes in bone turnover and increases in bone strength using the ovariectomized mature rat model of postmenopausal osteoporosis.