Cortical Bone Strength Research Articles

The effects of endurance exercise and caloric restriction on geometry and densitometry of cortical bone in adult male rats

Objective: To investigate the effects of calorie restriction and endurance exercise on cortical bone mineral density and geometry in adult male rats. Method: Sixty 26 weeks male Sprague Dawley rats (n=60) were randomly assigned to control (CON), 40% and 20% caloric restriction (CR40% and CR20%),endurance training (EXE) and pioglitazone (PIO) groups (n=12 for each group). The exercise intervention was consisted of a treadmill running training at speed of 16 m/min, 60 min/day and 5 days/week for nine weeks. The PIO rats were oral fed by pioglitazone at a dose of 10mg/kg b.w./day. After euthanasia, femoral bones were collected and subjected micro CT scanning for densitometric and geometric analyses. Result: The CR40%, CR20% and EXE groups were significant lower in body mass as compared to the CON and PIO group (p <0.05). There is no difference in the absolute BMD and BMC. And, none of cross-sectional geometry measurements showed difference among groups. However, when indices further divided by the body mass, the CON and PIO groups showed relatively lower values in most indices of densitometry (relative total and cortical BMD and BMC) as well as relatively lower cross-sectional parameters in cortical bone (including: cross-sectional area, cortical thickness and moment of inertia, etc.) (p <0.05). Conclusion Absolutely, rats treated with exercise, CR and pioglitazone treatment showed no different effects on cortical bone size and densitometry in adult male rats. However, the body weight reduction shown in exercise and CR groups made the bones of those animals relatively higher in cortical bone strength, size and density.

Adipose Tissue Infiltration of Bone Marrow and Skeletal Muscle in Children with Mild Spastic Cerebral Palsy

Non-ambulatory children with severe cerebral palsy (CP) have a high degree of adipose tissue (AT) infiltration which could play a role in the development of insulin resistance and fractures. The objective of this study was to determine the degree of AT infiltration within the bone marrow cavity of the middle tibia and within the surrounding muscle in ambulatory children with mild spastic CP (5-11 y) compared to typically developing controls matched for age and sex (n = 8/group). The concentration of AT in the bone marrow and muscle, and the intermuscular, subfascial and subcutaneous AT volume, muscle volume, cortical bone volume and bone strength (i.e., section modulus, Z and polar moment of inertia, J) were estimated using magnetic resonance imaging. Children with CP vs. controls had a higher (P < 0.05) concentration of AT in the bone marrow (83 ± 2 % vs. 81 ± 2 %) and muscle (27 ± 7 % vs. 18 ± 5 %). Children with CP vs. controls also had higher (P < 0.05) subfascial AT (357 %), and lower muscle volume (40%), cortical bone volume (26 %), Z (31 %) and J (38 %). Although not statistically significant (P = 0.07), children with CP vs. controls also had higher intermuscular AT (391 %). Whether the high concentration of AT in bone marrow and muscle during childhood are early indicators of insulin resistance and future fracture requires further investigation. Supported by the NIH(Grant HD071397-01).

Bone imaging and fracture risk assessment in kidney disease.

Fractures are more common and are associated with greater morbidity and morality in patients with kidney disease than in members of the general population. Thus, it is troubling that in chronic kidney disease (CKD) patients there has been a paradoxical increase in fracture rates over the past 20 years compared to the general population. Increased fracture incidence in CKD patients may be driven in part by the lack of screening for fracture risk. In the general population, dual energy X-ray absorptiometry (DXA) is the clinical standard to stratify fracture risk, and its use has contributed to decreases in fracture incidence. In contrast, in CKD, fracture risk screening with DXA has been uncommon due to its unclear efficacy in predicting fracture and its inability to predict type of renal osteodystrophy. Recently, several prospective studies conducted in patients across the spectrum of kidney disease have demonstrated that bone mineral density measured by DXA predicts future fracture risk and that clinically relevant information regarding fracture risk is provided by application of the World Health Organization cutoffs for osteopenia and osteoporosis to DXA measures. Furthermore, novel high-resolution imaging tools, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have been used to elucidate the effects of kidney disease on cortical and trabecular microarchitecture and bone strength and to identify potential targets for strategies that protect against fractures. This review will discuss the updated epidemiology of fractures in CKD, fracture risk screening by DXA, and the utility of state-of-the art imaging methods to uncover the effects of kidney disease on the skeleton.

Inhibition of CaMKK2 reverses age-associated decline in bone mass

Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2−/− mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral mid-shaft geometry, the mid-shaft cortical wall thickness and material bending stress remained similar among the cohorts, implying that regardless of treatment, the material properties of the bone remain similar. Thus, our cumulative results provide evidence for the pharmacological inhibition of CaMKK2 as a bone anabolic strategy in combating age-associated osteoporosis.

Prematurity and low birth weight lead to altered bone geometry, strength, and quality in children.

Prematurity and low birth weight are associated with a decrease in bone mass. Aim of the study was to investigate bone geometry, strength, and quality in children born at term small for gestational age (term SGA), premature appropriate for gestational age (prem AGA), and premature SGA (prem SGA). 91 patients (46 f, 45 m), mean age 11.28 years, height SDS 0.03 ± 0.21, and BMI SDS -0.31 ± 0.19. 20 were term SGA, 22 prem SGA, and 49 prem AGA. Bone geometry was assessed on the 2nd metacarpal bone, by evaluating the outer and inner diameter, the cortical area, medullary area, metacarpal index, cross-sectional area, and bone strength. Bone quality was evaluated by ultrasound and expressed as amplitude-dependent speed of sound and bone transmission time (BTT). Term SGA, prem SGA, and prem AGA had values of bone geometry, strength, and quality significantly lower than our reference range (p < 0.05). Findings in the three groups were similar, apart from BTT, which was significantly reduced in prem SGA (p < 0.05). Fat percentage was the main determinant of BTT. Children born either prematurely or SGA seem to have smaller and weaker bones. Those born both premature and SGA were the most affected.

Finite element analysis of the biomechanical effects of PEEK dental implants on the peri-implant bone

Dental implants are mostly fabricated of titanium. Potential problems associated with these implants are discussed in the literature, for example, overloading of the jawbone during mastication due to the significant difference in the elastic moduli of titanium (110GPa) and bone (≈1–30GPa). Therefore poly-ether-ether-ketone (PEEK) could represent an alternative biomaterial (elastic modulus 3–4GPa). Endolign® represents an implantable carbon fiber reinforced (CFR)-PEEK including parallel oriented endless carbon fibers. According to the manufacturer it has an elastic modulus of 150GPa. PEEK compounds filled with powders show an elastic modulus around 4GPa.The aim of the present finite element analysis was to point out the differences in the biomechanical behavior of a dental implant of Endolign® and a commercial powder-filled PEEK. Titanium served as control.These three materials were used for a platform-switched dental implant-abutment assembly, whereas Type 1 completely consisted of titanium, Type 2 of a powder-filled PEEK and Type 3 of Endolign®. A force of 100N was applied vertically and of 30° to the implant axis.All types showed a minimum safety factor regarding the yield strength of cortical bone. However, within the limits of this study the Type 2 implant showed higher stresses within the adjacent cortical bone than Type 1 and Type 3. These implant assemblies showed similar stress distributions.Endless carbon fibers give PEEK a high stability. Further investigations are necessary to evaluate whether there is a distinct amount of endless carbon fibers causing an optimal stress distribution behavior of CFR-PEEK.

Sclerostin inhibition prevents spinal cord injury-induced cancellous bone loss.

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n = 11-19/group) skeletally mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI + TE (7.0 mg/wk, im), or (D) 250 kilodyne SCI + Scl-Ab (25 mg/kg, twice weekly, sc) for 3 weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via μCT and histomorphometry) and distal femur (via μCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and platelike trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI + Scl-Ab and SCI + TE animals, whereas only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population.

Preparation and anti-osteoporotic activities in vivo of phosphorylated peptides from Antarctic krill (Euphausia superba)

Antarctic krill (Euphausia superba) protein serves as a novel sustainable protein source for human. Krill protein isolate was phosphorylated by the dry-heating method with sodium pyrophosphate. Phosphorylated peptides from Antarctic krill (PP-AKP) were obtained from phosphorylated protein through tryptic hydrolysis. Two types of phosphate bonds were introduced by phosphorylation, i.e. PO and PO bonds. The anti-osteoporotic activities of PP-AKP at two doses (400 and 800mg/kg body weight) were investigated with an osteoporotic rat model, which was established with bilateral ovariectomy surgery. Different doses of PP-AKP were given intraperitoneal injections to rats once a day with alendronate as a positive control. Phosphorylated peptides from Antarctic krill dose-dependently preserved bone mineral density in osteoporotic rats by increasing the degree of bone mineralization. Both trabecular and cortical bone strength in osteoporotic rats was significantly improved with PP-AKP treatment. The mechanism by which PP-AKP augmented bone mineral density and bone strength was relation to the reduction in osteoclast-mediated bone remodeling, as was supported by the decrease in bone resorption markers. Phosphorylated peptides from Antarctic krill could be developed as functional food or nutritional supplements.

Periostin expression contributes to cortical bone loss during unloading

Periostin (a product of Postn gene) is a matricellular protein which is increased in periosteal osteoblasts and osteocytes upon mechanical stimulation. We previously reported that periostin-deficient mice (Postn−/−) have low bone mass and a diminished response to physical activity due to a lack of sclerostin (a product of Sost gene) inhibition by mechanical loading. Here we hypothesized that periostin could play a central role in the control of bone loss during unloading induced by hindlimb suspension (HU).In Postn+/+ mice (wildtype littermate), HU significantly decreased femur BMD, as well as trabecular BV/TV and thickness (Tb.Th). Cortical bone volume and thickness at the femoral midshaft, also significantly decreased. These changes were explained by an inhibition of endocortical and periosteal bone formation activity and correlated with a decrease of Postn expression and a consecutive increase in Sost early after HU. Whereas trabecular bone loss in Postn−/− mice was comparable to Postn+/+ mice, HU did not significantly alter cortical bone microstructure and strength in Postn−/− mice. Bone formation remained unchanged in these mice, as Sost did not increase in the absence of periostin. In contrast, changes in Dkk1, Rankl and Opg expression in response to HU were similar to Postn+/+ mice, indicating that changes in periostin expression were quite specifically related to changes in Sost. In conclusion, HU inhibits periostin expression, which in turn plays an important role in cortical bone loss through an increase in Sost. These results further indicate that periostin is an essential mediator of cortical bone response to mechanical forces (loading and unloading).

Progressive Increases in Bone Mass and Bone Strength in an Ovariectomized Rat Model of Osteoporosis After 26 Weeks of Treatment With a Sclerostin Antibody

The effects of up to 26 weeks of sclerostin antibody (Scl-Ab) treatment were investigated in ovariectomized (OVX) rats. Two months after surgery, 6-month-old osteopenic OVX rats were treated with vehicle or Scl-Ab (25 mg/kg, sc, one time per week) for 6, 12, or 26 weeks. In vivo dual-energy x-ray absorptiometry analysis demonstrated that the bone mineral density of lumbar vertebrae and femur-tibia increased progressively through 26 weeks of Scl-Ab treatment along with progressive increases in trabecular and cortical bone mass and bone strength at multiple sites. There was a strong correlation between bone mass and maximum load at lumbar vertebra, femoral neck, and diaphysis at weeks 6 and 26. Dynamic histomorphometric analysis showed that lumbar trabecular and tibial shaft endocortical and periosteal bone formation rates (BFR/BS) increased and peaked at week 6 with Scl-Ab-treatment; thereafter trabecular and endocortical BFR/BS gradually declined but remained significantly greater than OVX controls at week 26, whereas periosteal BFR/BS returned to OVX control levels at week 26. In the tibia metaphysis, trabecular BFR/BS in the Scl-Ab treated group remained elevated from week 6 to week 26. The osteoclast surface and eroded surface were significantly lower in Scl-Ab-treated rats than in OVX controls at all times. In summary, bone mass and strength increased progressively over 26 weeks of Scl-Ab treatment in adult OVX rats. The early gains were accompanied by increased cortical and trabecular bone formation and reduced osteoclast activity, whereas later gains were attributed to residual endocortical and trabecular osteoblast stimulation and persistently low osteoclast activity.

Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model.

Collagen cross-linking is altered in many diseases of bone, and enzymatic collagen cross-links are important to bone quality, as evidenced by losses of strength after lysyl oxidase inhibition (lathyrism). We hypothesized that cross-links also contribute directly to bone fracture toughness. A mouse model of lathyrism using subcutaneous injection of up to 500 mg/kg β-aminopropionitrile (BAPN) was developed and characterized (60 animals across 4 dosage groups). Three weeks of 150 or 350 mg/kg BAPN treatment in young, growing mice significantly reduced cortical bone fracture toughness, strength, and pyridinoline cross-link content. Ratios reflecting relative cross-link maturity were positive regressors of fracture toughness (HP/[DHLNL + HLNL] r(2) = 0.208, p < 0.05; [HP + LP]/[DHNL + HLNL] r(2) = 0.196, p < 0.1), whereas quantities of mature pyridinoline cross-links were significant positive regressors of tissue strength (lysyl pyridinoline r(2) = 0.159, p = 0.014; hydroxylysyl pyridinoline r(2) = 0.112, p < 0.05). Immature and pyrrole cross-links, which were not significantly reduced by BAPN, did not correlate with mechanical properties. The effect of BAPN treatment on mechanical properties was dose specific, with the greatest impact found at the intermediate (350 mg/kg) dose. Calcein labeling was used to define locations of new bone formation, allowing for the identification of regions of normally cross-linked (preexisting) and BAPN-treated (newly formed, cross-link-deficient) bone. Raman spectroscopy revealed spatial differences attributable to relative tissue age and effects of cross-link inhibition. Newly deposited tissues had lower mineral/matrix, carbonate/phosphate, and Amide I cross-link (matrix maturity) ratios compared with preexisting tissues. BAPN treatment did not affect mineral measures but significantly increased the cross-link (matrix maturity) ratio compared with newly formed control tissue. Our study reveals that spatially localized effects of short-term BAPN cross-link inhibition can alter the whole-bone collagen cross-link profile to a measureable degree, and this cross-link profile correlates with bone fracture toughness and strength. Thus, cross-link profile perturbations associated with bone disease may provide insight into bone mechanical quality and fracture risk.

Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical micromorphology and bone strength.

A role for gut hormone in bone physiology has been suspected. We evidenced alterations of microstructural morphology (trabecular and cortical) and bone strength (both at the whole-bone--and tissue-level) in double incretin receptor knock-out (DIRKO) mice as compared to wild-type littermates. These results support a role for gut hormones in bone physiology. The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), have been shown to control bone remodeling and strength. However, lessons from single incretin receptor knock-out mice highlighted a compensatory mechanism induced by elevated sensitivity to the other gut hormone. As such, it is unclear whether the bone alterations observed in GIP or GLP-1 receptor deficient animals resulted from the lack of a functional gut hormone receptor, or by higher sensitivity for the other gut hormone. The aims of the present study were to investigate the bone microstructural morphology, as well as bone tissue properties, in double incretin receptor knock-out (DIRKO) mice. Twenty-six-week-old DIRKO mice were age- and sex-matched with wild-type (WT) littermates. Bone microstructural morphology was assessed at the femur by microCT and quantitative X-ray imaging, while tissue properties were investigated by quantitative backscattered electron imaging and Fourier-transformed infrared microscopy. Bone mechanical response was assessed at the whole-bone- and tissue-level by 3-point bending and nanoindentation, respectively. As compared to WT animals, DIRKO mice presented significant augmentations in trabecular bone mass and trabecular number whereas bone outer diameter, cortical thickness, and cortical area were reduced. At the whole-bone-level, yield stress, ultimate stress, and post-yield work to fracture were significantly reduced in DIRKO animals. At the tissue-level, only collagen maturity was reduced by 9 % in DIRKO mice leading to reductions in maximum load, hardness, and dissipated energy. This study demonstrated the critical role of gut hormones in controlling bone microstructural morphology and tissue properties.

Effect of sequential treatments with alendronate, parathyroid hormone (1–34) and raloxifene on cortical bone mass and strength in ovariectomized rats

Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear. MethodsSix-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1–34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples. ResultsEight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties. SummarySequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.

Analysis of Cortical Bone Structures in Perimenopausal Female Patients With Recent Fragility Fractures

Aims: The aim of this study was to investigate trabecular and cortical bone microstructure in perimenopausal patients with atraumatic peripheral or vertebral fractures. We hypothesize that in perimenopausal women cortical bone is more affected by osteoporosis than trabecular bone. Methods: We consecutively investigated 26 perimenopausal treatment naive female patients (mean age: 47.8 yrs) with peripheral fractures (PG) and compared them to ageand sex-matched healthy controls (CG; n538; mean age 42.7 yrs). Patients had an average of two atraumatic fractures, but were otherwise healthy. The distal radius and the ultradistal tibia of all patients were scanned on an HRpQCT scanner (XtremeCT, SCANCO Medical, Br€uttisellen, Switzerland). Trabecular bone volume fraction (BV/TV) from the volumetric BMD of the trabecular compartment (Tb.BMD), the peripheral region adjacent to the cortex (pTb.BMD) and the central trabecular region (mTb.BMD) were analyzed. From the binary trabecular ridge image, trabecular number (Tb.N) was measured using the direct 3D distance transform approach. Based on the densitometric BV/TV and direct Tb.N, trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were derived using traditional plate model assumptions, as has been described previously (Boutroy et al., JCEM 2005). To assess cortical bone microarchitecture, the trabecular and cortical compartment were segmented by automated algorithm (Burghardt et al., JBMR 2009). We analyzed cortical BMD (Ct.BMD), cortical porosity (Ct.Po), cortical pore volume (Ct.Po.V), cortical pore diameter (Ct.Po.Dm) and cortical pore diameter distribution (Ct.Po.Dm.SD). Results: Structural analysis by HR-pQCT showed significant differences between patients and healthy controls regarding cortical but not trabecular parameters at both sites. At the radius patients had increased cortical pore volume (7.74 4.97mm vs. 5.29 3.78; p!0.01), increased cortical pore diameter (0.17 0.03mm vs. 0.15 0.02mm; p! 0.001) and an increased distribution of cortical pore diameters (7 3% vs. 4 3%; p!0.01) compared to controls. In addition, at the tibia cortical pore volume (61.15 30.66mm; p!0.01) and also cortical porosity (7 4% vs. 4 3%; p!0.01) were significantly increased. Strong correlations of cortical parameters were found between the tibia and radius. In addition, most cortical structure parameters were correlated with age in patients and controls. Conclusion: Our results suggest that bone fragility and fracture susceptibility in perimenopausal females are likely to contribute to poor cortical bone strength and increased cortical porosity. However, HR-pQCT resolution is limited and cortical porosity, analyzed by different algorithm, was reported to be much higher. Disclosure of Interest: None Declared

Identification of anisotropic tensile strength of cortical bone using Brazilian test

For a proper analysis of cortical bone behaviour, it is essential to take into account both the elastic stiffness and the failure criteria. While ultrasound methods allow complete identification of the elastic orthotropic coefficients, tests used to characterise the various failure mechanisms and to identify the brittle tensile strength in all directions are currently inadequate. In the present work we propose the Brazilian test as a complement to conventional tensile tests. In fact, this experimental technique, rarely employed in the biomechanics field, has the potential to provide an accurate description of the anisotropic strength of cortical bone. Additionally, it allows us to assess the scale influence on failure behaviour which may be attributed to an intrinsic length in correlation with the cortical bone microstructure. In order to correctly set up the Brazilian test, several aspects such as the machining, the geometrical parameters of the specimen and the loading conditions were determined. The finite element method was used to evaluate the maximal tensile stress at the centre of a 2D anisotropic elastic specimen as a simple function of the loading. To validate the protocol, the Brazilian test was carried out on 29 cortical bovine cylindrical specimens with diameters ranging from 10mm to 4mm.

Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical microarchitectures and bone strength.

Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical microarchitectures and bone strength.

Serum Estradiol Levels Are Inversely Associated With Cortical Porosity in Older Men

Context:The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography, remains unknown in elderly men.Objective:The objective of the study was to examine the associations between serum sex steroids and bone microstructural parameters in older men.Methods:Trabecular and cortical bone microstructure at the tibia was measured by high-resolution peripheral quantitative computed tomography in 440 men (mean 80 y of age) participating in the population-based Osteoporotic Fractures in Men Sweden cohort. Serum levels of E2 and T were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations.Results:Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake, and smoking. Models including both serum E2 and T demonstrated that E2 (standardized β = −.12, P < .05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized β = −.12, P < .05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in the age-adjusted models, but this association did not remain significant after further adjustment.Conclusions:Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly, by increasing cortical porosity and thereby increase fracture risk in older men.

G59 Bone microarchitecture and strength in obese children – a new insight into fracture risk

IntroductionObese children have a greater fracture risk. Studies utilising DXA and pQCT have demonstrated that bone mass and size relative to body size is reduced in obese children. However, these...

Physical activity when young provides lifelong benefits to cortical bone size and strength in men

The skeleton shows greatest plasticity to physical activity-related mechanical loads during youth but is more at risk for failure during aging. Do the skeletal benefits of physical activity during youth persist with aging? To address this question, we used a uniquely controlled cross-sectional study design in which we compared the throwing-to-nonthrowing arm differences in humeral diaphysis bone properties in professional baseball players at different stages of their careers (n = 103) with dominant-to-nondominant arm differences in controls (n = 94). Throwing-related physical activity introduced extreme loading to the humeral diaphysis and nearly doubled its strength. Once throwing activities ceased, the cortical bone mass, area, and thickness benefits of physical activity during youth were gradually lost because of greater medullary expansion and cortical trabecularization. However, half of the bone size (total cross-sectional area) and one-third of the bone strength (polar moment of inertia) benefits of throwing-related physical activity during youth were maintained lifelong. In players who continued throwing during aging, some cortical bone mass and more strength benefits of the physical activity during youth were maintained as a result of less medullary expansion and cortical trabecularization. These data indicate that the old adage of "use it or lose it" is not entirely applicable to the skeleton and that physical activity during youth should be encouraged for lifelong bone health, with the focus being optimization of bone size and strength rather than the current paradigm of increasing mass. The data also indicate that physical activity should be encouraged during aging to reduce skeletal structural decay.

Micro-architectural changes in cancellous bone differ in female and male C57BL/6 mice with high-fat diet-induced low bone mineral density

The relationship between fat and bone mass at distinct trabecular and cortical skeletal compartments in a high-fat diet (HFD) model was studied. For this, C57BL/6 mice were assigned to four groups of eight animals each. Two groups, each of males and females, received a standard chow diet while the remaining other two groups received the HFD for a period of 10 weeks. Male mice on the HFD were heavier and gained more weight (15·8%; P< 0·05) v. those on the control diet or when compared with the female rats fed the HFD. We observed an increased lipid profile in both males and females, with significantly higher lipid levels (about 20-25%; P<0·01) in males. However, glucose intolerance was more pronounced in females than males on the HFD (about 30%; P<0·05). The micro-architectural assessment of bones showed that compared with female mice on the HFD, male mice on the HFD showed more deterioration at the trabecular region. This was corroborated by plasma osteocalcin and carboxy-terminal collagen crosslinks (CTx) levels confirming greater loss in males (about 20%; P<0·01). In both sexes cortical bone parameters and strength remained unchanged after 10 weeks of HFD treatment. The direct effect of the HFD on bone at the messenger RNA level in progenitor cells isolated from femoral bone marrow was a significantly increased expression of adipogenic marker genes v. osteogenic genes. Overall, the present data indicate that obesity induced by a HFD aggravates bone loss in the cancellous bone compartment, with a greater loss in males than females, although 10 weeks of HFD treatment did not alter cortical bone mass and strength in both males and females.