Higher Trabecular Thickness Research Articles

Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes bone length, regulates cortical and trabecular bone mass, and maintains growth plate architecture and width in a sex- and site-specific manner in mice

Tartrate-resistant acid phosphatase (TRAP) serum levels reflect osteoclast number, bone remodeling activity, and fracture risk. Deletion or loss of function of TRAP results in short stature in mice and man. Yet, the impact and mechanisms of TRAP for the site- and sex-specific development of bone and cartilage is not well understood. Here, we use a global TRAP knockout (TRAPKO) and wildtype littermate control (WT) mice of both sexes to investigate TRAP as a possible sex- and site-specific regulator of bone and growth plate development. TRAPKO mice of both sexes weighed less and had shorter tibial length than their WT, features that were more accentuated in male than female TRAPKO mice. These changes were not associated with a general reduction in growth as not all organs displayed a proportionally lower mass, and serum IGF-1 was unchanged. Using μCT and site-specificity analysis of the cortical bone revealed wider proximal tibia, a higher trabecular thickness, and lower trabecular separation in male TRAPKO compared to WT mice, an effect not seen in female mice. Histomorphometric analysis revealed that the growth plate height as well as height of terminal hypertrophic chondrocytes were markedly increased, and the number of columns was decreased in TRAPKO mice of both sexes. These effects were more accentuated in female mice. Proliferation and differentiation of bone marrow derived macrophages into osteoclasts, as well as C-terminal cross links were normal in TRAPKO mice of both sexes. Collectively, our results show that TRAP regulates bone and cartilage development in a sex-and site-specific manner in mice.

Risk Factors for Bone Microarchitecture Impairments in Older Men with Type 2 Diabetes - The MrOS Study.

Impaired bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), may contribute to bone fragility in type 2 diabetes (T2DM) but data on men are lacking. To investigate the association between T2DM and HR-pQCT parameters in older men. HR-pQCT scans were acquired on 1794 participants in the Osteoporotic Fractures in Men (MrOS) study. T2DM was ascertained by self-report or medication use. Linear regression models, adjusted for age, race, BMI, limb length, clinic site, and oral corticosteroid use, were used to compare HR-pQCT parameters by diabetes status. Among 1777 men, 290 had T2DM (mean age 84.4 years). T2DM men had smaller total cross-sectional area (Tt.AR) at the distal tibia (p=0.028) and diaphyseal tibia (p=0.025), and smaller cortical area at the distal (p= 0.009) and diaphyseal tibia (p= 0.023). Trabecular indices and cortical porosity were similar between T2DM and non-T2DM. Among men with T2DM, in a model including HbA1c, diabetes duration, and insulin use, diabetes duration ≥ 10 years, compared with <10 years, was significantly associated with higher cortical porosity but with higher trabecular thickness at the distal radius. Insulin use was significantly associated with lower cortical area and thickness at the distal radius and diaphyseal tibia and lower failure load at all three scan sites. Lower cortical area, cortical thickness, total BMD, cortical BMD, and failure load of the distal sites were associated with increased risk of incident non-vertebral fracture in T2DM. Older men with T2DM have smaller bone size compared to non-T2DM, which may contribute to diabetic skeletal fragility. Longer diabetes duration was associated with higher cortical porosity and insulin use with cortical bone deficits and lower failure load.

Iron status is associated with tibial structure and vitamin D metabolites in healthy young men

The influence of iron on collagen synthesis and vitamin D metabolism has implications for bone health. This cross-sectional observational study investigated associations between markers of iron status and tibial structure, vitamin D metabolites, and circulating biochemical markers of bone metabolism in young healthy men. A total of 343 male British Army recruits participated (age 22 ± 3 y, height 1.77 ± 0.06 m, body mass 75.5 ± 10.1 kg). Circulating biochemical markers of iron status, vitamin D metabolites, and bone metabolism, and tibial structure and density by high-resolution peripheral quantitative computed tomography scans (HRpQCT) were measured in participants during week 1 of basic military training. Associations between markers of iron status and HRpQCT outcomes, bone metabolism, and vitamin D metabolites were tested, controlling for age, height, lean body mass, and childhood exercise volume. Higher ferritin was associated with higher total, trabecular, and cortical volumetric bone mineral density, trabecular volume, cortical area and thickness, stiffness, and failure load (all p ≤ 0.037). Higher soluble transferrin receptor (sTfR) was associated with lower trabecular number, and higher trabecular thickness and separation, cortical thickness, and cortical pore diameter (all p ≤ 0.033). Higher haemoglobin was associated with higher cortical thickness (p = 0.043). Higher ferritin was associated with lower βCTX, PINP, total 25(OH)D, and total 24,25(OH)2D, and higher 1,25(OH)2D:24,25(OH)2D ratio (all p ≤ 0.029). Higher sTfR was associated with higher PINP, total 25(OH)D, and total 24,25(OH)2D (all p ≤ 0.025). The greater density, size, and strength of the tibia, and lower circulating concentrations of markers of bone resorption and formation with better iron stores (higher ferritin) are likely as a result of the direct role of iron in collagen synthesis.

Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.

Advancing age is the strongest risk factor for osteoporosis and skeletal fragility. Rapamycin is an FDA-approved immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) complex, extends lifespan, and protects against aging-related diseases in multiple species; however, the impact of rapamycin on skeletal tissue is incompletely understood. We evaluated the effects of a short-term, low-dosage, interval rapamycin treatment on bone microarchitecture and strength in young-adult (3 mo old) and aged female (20 mo old) C57BL/6 mice. Rapamycin (2mg/kg body mass) was administered via intraperitoneal injection 1×/5d for a duration of 8wk; this treatment regimen has been shown to induce geroprotective effects while minimizing the side effects associated with higher rapamycin dosages and/or more frequent or prolonged delivery schedules. Aged femurs exhibited lower cancellous bone mineral density, volume, trabecular connectivity density and number, higher trabecular thickness and spacing, and lower cortical thickness compared to young-adult mice. Rapamycin had no impact on assessed microCT parameters. Flexural testing of the femur revealed that both yield strength and ultimate strength were lower in aged mice compared to young-adult mice. There were no effects of rapamycin on these or other measures of bone biomechanics. Age, but not rapamycin, altered local and global measures of bone turnover. These data demonstrate that short-term, low-dosage interval rapamycin treatment does not negatively or positively impact the skeleton of young-adult and aged mice.

Dual-functional coatings on magnesium alloys: Enhancing corrosion behavior under stress and osteogenic effect in osteoporotic rats

Magnesium-based implants are subjected to complicated stresses during implantation in the human body. In this case, they undergo stress-induced corrosion and usually lead to early breakage or disintegration of implants. Calcium phosphate compounds have been used as coatings, bone cement and drug carrier in orthopedic application. Their success has been expanded to Mg alloys. Calcium phosphate-based coatings succeeded in corrosion control and osteointegration of Mg alloys in a big extent. However, their protective effect under stress condition is questionable considering the brittle nature. With the assistance of high pH microenvironment near Mg alloy surface, calcium phosphate coatings have the self-repair potential via the dissolution-precipitation mechanism. Inspired by this phenomenon, strontium doped hydroxyapatite (Sr-HA) coatings with higher solubility have been prepared on the surface of Mg alloys. Sr-HA coatings served as not only a physical barrier effect to postpone pitting formation, but also provide ion supplement to seal the cracks initiated during tensile deformation. The results obtained in slow strain rate tensile test (SSRT) demonstrated improved corrosion and mechanical behaviors of Sr-HA coated Mg alloys. Specifically, the elongation of Sr-HA coated alloy increased by 56.7 and 35.2% as compared to the bare and HA coated one in DMEM. In ovariectomized rats, the implants exhibited only 2.7–5.6% reduction of implant volume after 12 weeks implantation. Sr-HA coating further increased early new bone formation than HA coated implants. 12 weeks post-implantation, a large amount of bony tissue with higher trabecular thickness and hardness was formed adjacent to the Sr-HA coated implants. This study demonstrated the efficiency of a rapid dissolved Sr-HA coating on the corrosion behavior of Mg alloys under mechanical loading and the osteogenesis in ovariectomized rats. It therefore holds a promising practical significance for the future coating design strategy for Mg alloys when trying to expand their application range to locations with higher loading conditions.

Morphological analysis of third metacarpus cartilage and subchondral bone in Thoroughbred racehorses: An ex vivo study.

Racehorses are exposed to repetitive overload during training and competition, causing joint hyperextension, tissue fatigue, and ultimately skeletal failure. Some degree of bone changes, such as sclerosis, are expected in equine athletes, as adaptation to the biomechanical rigors of training and racing. Understanding the imaging characteristics of the equine joint surface and subchondral bone would allow earlier detection of injuries or adaptation, improving prognosis and training programs. This study sought to describe the joint surface structural patterns and the periarticular structures of the third metacarpal bone (MC3). Both forelimbs of eight horses engaged in daily training programs, aged 3-5 years, which were euthanized for reasons unrelated to the metacarpophalangeal (MCP) joints, were collected. Specimens were evaluated through macroscopic inspection, radiography, ultrasonography, and microscopic examinations, such as optical microscopy and microtomography. Analysis of the microtomography images showed that 50% of the samples had higher trabecular thickness in the lateral condyle. Comparison of each imaging examination revealed that ultrasound images were most closely related to the histological examination (p=.29) in terms of sensitivity, while macroscopic and radiographic examinations differed most between evaluators. Finally, the irregularities and modifications observed in the articular cartilage surface and subchondral bone were normal adaptations of the anatomical structures of trained racehorses, which should be considered during clinical examination.

Follistatin-like 1 suppresses osteoblast differentiation of bone marrow mesenchymal cells during inflammation

ObjectiveThe current study aimed to explore the effect of Follistatin-like 1 (FSTL1) on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in an inflammatory environment. DesignAnimal models of FSTL1-deficiency and wild-type mice were used, and the micro-CT images of the femoral head were evaluated. Mouse bone marrow mesenchymal stem cells were treated with various concentrations of recombinant FSTL1 (rFSTL1) in an inflammatory environment in vitro. Meanwhile, overexpression or knockdown of FSTL1 through lentiviral transfection was performed. Alkaline phosphatase (ALP) activity was tested, and Alizarin Red staining (ARS) was performed to evaluate osteogenic differentiation ability. The mRNA expression level of osteogenesis-related genes was detected by RT-qPCR. ResultsIn vivo experiments revealed a higher number of femoral skulls, higher trabecular thickness, smaller trabecular space, and less osteoporosis in FSTL1-knockdown mice than in the wild-type mice. The BMSCs with overexpression of FSTL1 or those treated with recombinant FSTL1 (rFSTL1) showed suppression of ALP activity, calcium nodule formation, and expression of osteogenesis-related genes osteopontin (OPN), osteocalcin (OCN), collagen type I alpha 1 (Col1α1), and more importantly, rFSTL1 functions in a dose-dependent manner. In contrast, FSTL1 knockdown promoted the osteogenesis activity and the expression of these osteogenesis-related genes in vitro. ConclusionsFSTL1 is an osteogenic suppressor that inhibits the osteogenic differentiation of BMSCs during inflammation and it can be a new target for bone regeneration.

Bone Histomorphometry of Femoral Head Cancellous Bone in Patients Who Underwent Total Hip Arthroplasties due to Destructive Hip in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) affects the hip joints. The microarchitecture of the cancellous bone in RA-affected hip joints has been unclear. Here we investigated the bone metabolism changes in the subcapital cancellous bone of destructive hips of RA patients (n=26 patients; 28 hip joints) which were classified by Larsen grade on X-ray into the groups: destructive hip (Des) (Larsen grade IV, n=18) and neck fracture (Fx) (Larsen grade 0 or 1, n=10). The femoral heads of the Des-group showed significantly higher trabecular thickness versus those of the Fx-group (179±30.8 vs. 151±23.5 μm, p=0.02). The Des-group had significantly higher osteoid volume/tissue volume (OV/TV) and osteoid volume/bone volume (OV/BV) ratios than the Fx-group (OV/TV: 0.72±0.70% vs. 0.27±0.32%, p=0.028; OV/BV: 2.96±2.85% vs. 1.24±1.31%, p=0.039). The osteoblast and osteoclast surface areas of the Des-group were remarkably higher than those of the Fx-group (9.80±10.9 vs. 0.15±0.15%, p=0.0005; 0.34±0.48 vs. 0.06±0.06%, p=0.0285, respectively). The T-scores of hip (femoral neck) bone mineral density (BMD) of the Fx-group were significantly lower versus those of the Des-group (-3.1±0.76 vs. -1.6±1.17, p<0.01). Increased osteoid and resorption parameters and higher femoral neck BMD demonstrate a high bone-turnover state in response to destructive changes in the hips of RA patients.

Bone quality analysis of jaw bones in individuals with type 2 diabetes mellitus-post mortem anatomical and microstructural evaluation.

With the higher risk of dental implant failure with type 2 diabetes mellitus (T2DM), there is a need to characterize the jaw bones in those individuals. The aim of this post mortem study was to compare jaw bone quality of individuals with T2DM to healthy controls. Bone cores from the edentulous lower first molar region and the region of mandibular angle were collected from male individuals with T2DM (n = 10, 70.6 ± 4.5years) and healthy controls (n = 11, 71.5 ± 3.8years) during autopsy. Within the T2DM, a subgroup treated with oral antidiabetics (OAD) and one on insulin were identified. Bone quality assessment encompassed evaluation of bone microstructure, matrix composition, and cellular activity, using microcomputed tomography (micro-CT), quantitative backscattered electron imaging (qBEI), Raman spectroscopy, and bone histomorphometry. In the mandibular angle, T2DM showed 51% lower porosity of the lingual cortex (p = 0.004) and 21% higher trabecular thickness (p = 0.008) compared to control. More highly mineralized bone packets were found in the buccal cortex of the mandibular angle in insulin-treated compared to OAD-treated T2DM group (p = 0.034). In the molar region, we found higher heterogeneity of trabecular calcium content in T2DM insulin compared to controls (p = 0.015) and T2DM OAD (p = 0.019). T2DM was associated with lower osteocyte lacunar size in the trabecular bone of the molar region (vs. control p = 0.03). Alterations in microstructure, mineralization, and osteocyte morphology were determined in jaw bone of individuals with T2DM compared to controls. Future studies will have to verify if the mild changes determined in this study will translate to potential contraindications for dental implant placements.

Effects of efavirenz and tenofovir on bone tissue in Wistar rats.

Clinical trials indicate an increased risk of osteoporosis and bone fractures in people infected with human immunodeficiency virus (HIV). The pathogenesis of bone disturbances in HIV-positive patients is unknown, but it is suggested that antiretroviral drugs may be involved. To assess the effects of efavirenz (EF) and tenofovir (T) on bone remodeling in rats. The study involved 36 male Wistar rats divided into 3 groups, receiving normal saline (control group - group C), efavirenz (group EF) or tenofovir disoproxil (group T). After 24 weeks of the study, the following observations were made: In blood serum of the EF group compared to group C, there were increased levels of tartrate-resistant acid phosphatase form 5b (TRAP) and inorganic phosphorus. In the densitometric examination, group T showed a lower total body (TB) bone mineral density (BMD) than group C. In the immunohistochemical assessment, group EF showed a higher intensity and extension of anti-tartrate resistant acid phosphatase antibodies (abTRAP) compared to group C. In the histopathological examination of the second lumbar vertebra (L2), group EF showed a lower bone surface/volume ratio (BS/BV) and higher trabecular thickness (Tb.Th) than the control group. In the histopathological examination of the femur, a lower bone surface/tissue volume (BS/TV) and lower trabecular number (Tb.N) were found in group T compared to in group C. A lower value of the Young's modulus was observed in the four-point bending trial in groups EF and T compared to group C. The results of this study indicate that EF affects bone microarchitecture and leads to impaired biomechanical properties of bones in rats. Additionally, the negative effect of T on bone tissue was confirmed.

Trabecular architecture in the sciuromorph femoral head: allometry and functional adaptation

BackgroundSciuromorpha (squirrels and close relatives) are diverse in terms of body size and locomotor behavior. Individual species are specialized to perform climbing, gliding or digging behavior, the latter being the result of multiple independent evolutionary acquisitions. Each lifestyle involves characteristic loading patterns acting on the bones of sciuromorphs. Trabecular bone, as part of the bone inner structure, adapts to such loading patterns. This network of thin bony struts is subject to bone modeling, and therefore reflects habitual loading throughout lifetime. The present study investigates the effect of body size and lifestyle on trabecular structure in Sciuromorpha.MethodsBased upon high-resolution computed tomography scans, the femoral head 3D inner microstructure of 69 sciuromorph species was analyzed. Species were assigned to one of the following lifestyle categories: arboreal, aerial, fossorial and semifossorial. A cubic volume of interest was selected in the center of each femoral head and analyzed by extraction of various parameters that characterize trabecular architecture (degree of anisotropy, bone volume fraction, connectivity density, trabecular thickness, trabecular separation, bone surface density and main trabecular orientation). Our analysis included evaluation of the allometric signals and lifestyle-related adaptation in the trabecular parameters.ResultsWe show that bone surface density, bone volume fraction, and connectivity density are subject to positive allometry, and degree of anisotropy, trabecular thickness, and trabecular separation to negative allometry. The parameters connectivity density, bone surface density, trabecular thickness, and trabecular separation show functional signals which are related to locomotor behavior. Aerial species are distinguished from fossorial ones by a higher trabecular thickness, lower connectivity density and lower bone surface density. Arboreal species are distinguished from semifossorial ones by a higher trabecular separation.ConclusionThis study on sciuromorph trabeculae supplements the few non-primate studies on lifestyle-related functional adaptation of trabecular bone. We show that the architecture of the femoral head trabeculae in Sciuromorpha correlates with body mass and locomotor habits. Our findings provide a new basis for experimental research focused on functional significance of bone inner microstructure.

Glycemic control protects against trabecular bone microarchitectural damage in a juvenile male rat model of streptozotocin-induced diabetes

ABSTRACTPurpose: To determine which features of the bone microarchitecture are affected by established diabetes mellitus (DM) and the effectiveness of glycemic control in the protection of bone tissue. Material and methods: Sixty juvenile Wistar male rats were divided into three groups of 20 animals: a control group (C) that included healthy animals, a diabetic group (D) that included animals with induced diabetes, and a controlled diabetic group (CD) that included animals with induced diabetes that were treated with insulin. The animals were euthanized at the periods of 6 and 8 weeks after the induction of diabetes (10 animals per group/period). Vertebral L4 specimens were submitted to μCT analysis to assess the following parameters of the bone microarchitecture: bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular spacing (Tb.Sp). Results: The D group exhibited lower values of BV/TV (%) and numbers of trabeculae compared with the C group at 6 and 8 weeks and compared with the CD group at 8 weeks. The CD group exhibited higher trabecular thickness values compared with the D group at 8 weeks. There were no differences between the groups regarding the spaces between the trabeculae. Conclusion: Induced diabetes affected the microarchitecture of the trabecular bone of the vertebrae by reducing the values of the majority of the parameters in relation to those of the control group. Glycemic control with insulin appears to protect bones from the effects of the hyperglycemia.

The repair of full-thickness articular cartilage defect using intra-articular administration of N-acetyl-D-glucosamine in the rabbit knee: randomized controlled trial.

BackgroundAlthough various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached. Glucosamine (GlcN) is widely used as a nutritional supplement. However, the clinical- evidence-based outcome of GlcN administration remains controversial. N-acetyl-d-glucosamine (GlcNAc), a derivative of GlcN, shows chondroprotective activity and mediates the activation of articular chondrocytes. Therefore, we investigated the effect of intra-articular administration of GlcNAc in rabbits’ knee joints with experimental full-thickness articular cartilage (FTAC) defects.MethodsTwelve male adult New Zealand white rabbits, providing 24 knees, were used in this study. FTAC defects were created in the high-weight-bearing area of the medial femoral condyles of bilateral knees. All rabbits were randomly allocated to analysis at postsurgical week 4 or postsurgical week 12. In the week 4 group, rabbits’ knees (six per group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 3 weeks, beginning 1 week postoperatively. In the week 12 group, the rabbits’ knees (six in each group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 4 weeks, beginning 1 week postoperatively. Rabbits were sacrificed at 4 or 12 weeks after surgery for macroscopic, histological and radiological examinations of the knee joints.ResultsAll rabbits had no systemic or local adverse effects. The saline and GlcNAc groups showed visible differences in healing of the FTAC defect at the end of testing. At week 4, the GlcNAc group had a higher level of collagen type II (COL II) and showed up-regulated production of transforming growth factor (TGF)-β2 and TGF-β3, suggesting the involvement of endogenous growth factors. At week 12, the GlcNAc group displayed formation of hyaline-like cartilage regeneration with mature chondrocytes (SOX9+), robust glycosaminoglycan (GAG) content, and positive COL II content in both the adjacent cartilage and reparative sites. However, the saline group demonstrated mainly fibrocartilage scar tissue, indicating COL I expression. Furthermore, the GlcNAc group had significantly higher bone volume per tissue volume and higher trabecular thickness than the saline group.ConclusionsIntra-articular GlcNAc may promote the repair of experimental FTAC defects in the rabbit knee joint model.

Regional variations in trabecular architecture of the lumbar vertebra: Associations with age, disc degeneration and disc space narrowing

Previous studies suggest that age and disc degeneration are associated with variations in vertebral trabecular architecture. In particular, disc space narrowing, a severe form of disc degeneration, may predispose the anterior portion of a vertebra to fracture. We studied 150 lumbar vertebrae and 209 intervertebral discs from 48 cadaveric lumbar spines of middle-aged men to investigate regional trabecular differences in relation to age, disc degeneration and disc narrowing. The degrees of disc degeneration and narrowing were evaluated using radiography and discography. The vertebrae were dried and scanned on a μCT system. The μCT images of each vertebral body were processed to include only vertebral trabeculae, which were first divided into superior and inferior regions, and further into central and peripheral regions, and then anterior and posterior regions. Structural analyses were performed to obtain trabecular microarchitecture measurements for each vertebral region. On average, the peripheral region had 12–15% greater trabecular bone volume fraction and trabecular thickness than the central region (p<0.01). Greater age was associated with better trabecular structure in the peripheral region relative to the central region. Moderate and severe disc degeneration were associated with higher trabecular thickness in the peripheral region of the vertebral trabeculae (p<0.05). The anterior region was of lower bone quality than the posterior region, which was not associated with age. Slight to moderate narrowing was associated with greater trabecular bone volume fraction in the anterior region of the inferior vertebra (p<0.05). Similarly, greater disc narrowing was associated with higher trabecular thickness in the anterior region (p<0.05). Better architecture of peripheral trabeculae relative to central trabeculae was associated with both age and disc degeneration. In contrast to the previous view that disc narrowing stress-shields the anterior vertebra, disc narrowing tended to associate with better trabecular architecture in the anterior region, as opposed to the posterior region.

Tunable dual growth factor delivery from polyelectrolyte multilayer films

A promising strategy to accelerate joint implant integration and reduce recovery time and failure rates is to deliver a combination of certain growth factors to the integration site. There is a need to control the quantity of growth factors delivered at different times during the healing process to maximize efficacy. Polyelectrolyte multilayer (PEM) films, built using the layer-by-layer (LbL) technique, are attractive for releasing controlled amounts of potent growth factors over a sustained period. Here, we present PEM films that sequester physiological amounts of osteogenic rhBMP-2 (recombinant human bone morphogenetic protein - 2) and angiogenic rhVEGF 165 (recombinant human vascular endothelial growth factor) in different ratios in a degradable [poly(β-amino ester)/polyanion/growth factor/polyanion] LbL tetralayer repeat architecture where the biologic load scaled linearly with the number of tetralayers. No burst release of either growth factor was observed as the films degraded. The release of rhBMP-2 was sustained over a period of 2 weeks, while rhVEGF 165 eluted from the film over the first 8 days. Both growth factors retained their efficacy, as quantified with relevant in vitro assays. rhBMP-2 initiated a dose dependent differentiation cascade in MC3T3-E1S4 pre-osteoblasts while rhVEGF 165 upregulated HUVEC proliferation, and accelerated closure of a scratch in HUVEC cell cultures in a dose dependent manner. In vivo, the mineral density of ectopic bone formed de novo by rhBMP-2/rhVEGF 165 PEM films was approximately 33% higher than when only rhBMP-2 was introduced, with a higher trabecular thickness, which would indicate a decrease in the risk of osteoporotic fracture. Bone formed throughout the scaffold when both growth factors were released, which suggests more complete remodeling due to an increased local vascular network. This study demonstrates a promising approach to delivering precise doses of multiple growth factors for a variety of implant applications where control over spatial and temporal release profile of the biologic is desired.

Gender Differences in Bone Adapting to Endurance Training in Wistar Rats

PURPOSE: To investigate the gender differences in bone material properties adapting to endurance training. METHODS: Wistar rats (7 weeks old) were randomly divided to male and female control groups (MCON and FCON, n=10 for each) and male and female exercise groups (MEXE and FEXE, n=11 for each). Animals in exercise groups subjected to an 8-week endurance running training with a protocol of 15 ∼ 28m/min, 60min/day and 5days/week. Two-way (gender×exercise) ANOVA was used for statistical analysis (α=.05). RESULTS: Significant main effects in gender (p<.001) and exercise (p<.001) were shown in body weight (BW), that male rats were higher than female rats (382.8±5.8 vs. 282.6±5.9 g) and exercise rats were lower than non-exercise rats (316.1±5.8 vs. 349.3±6.0 g).Simple main effects analysis showed that only the MEXE group was significantly lower in BW than the MCON group (353.5±8.0 vs. 412.1±8.4). In biomaterial properties, femora of male rats were significantly higher in yield load (YL, 217±4.9 vs. 147.6±4.9 N), ultimate load (UL, 249.2±6.0 vs. 165.2±6.0 N), yield load energy (YL energy, 54.5±2.1 vs. 37.3±2.1 mJ), ultimate load energy (UL energy, 100.8±4.9 vs. 68.3±4.9 mJ), post-yield energy (PY energy, 46.3±4.7 vs. 31.0±4.7 mJ) and stiffness (529.2±20.7 vs. 385.6±20.7 mm/N) as compared to female rats. Conversely, after eliminating the factor of tissue size, male rats were significant lower in yield stress (YS, 151.8±3.9 vs. 183.4±3.9 MPa) and Young's modulus (4.9±0.3 vs. 7.7±0.3 GPa). In the main effects for exercise, exercise rats were lower than control rats in CSMI (12.3±0.6 vs. 14.4±0.6 mm4), cortical area (7.4±0.2 vs. 8.1±0.2 mm2), YL (174.9±4.9 vs. 189.8 .(N 6.0±215.9.vs 6.0±198.5)UL,(N 4.9±3.0±58.8.vs 3.0±50.2)Simple main effect analysis showed that YL energy was significant lower in the MEXE group as compared to the MCON group 0.1±7.0)and phosphorous (dl/mg 0.1±10.2.vs 0.1±8.8)Serum calcium.(mJ vs. 6.4±0.1 mg/dl) were significantly lower and higher in male rats, respectively. In histomorphometry, male rats showed significantly lower bone volume ratio (17.0±1.2 vs. 20.7±1.1%) but higher trabecular thickness (110.6±1.6 vs. 40.8±1.5μm). CONCLUSIONS: Bone material properties adapting to endurance training were gender-dependant without showing disturbances in status of bone metabolism.

Increased bone strength is associated with improved bone microarchitecture in intact female rats treated with strontium ranelate: A finite element analysis study

Strontium ranelate has been previously shown to act on bone metabolism and to be effective in postmenopausal osteoporosis treatment by preventing vertebral and non-vertebral fractures. Animal studies explicitly demonstrated that bone strength was improved with strontium ranelate treatment, but the contribution of either improved bone microarchitecture or intrinsic quality of the bone tissue is not clear. Therefore, the purpose of this research was to address this issue by using the unique capability of finite element (FE) analysis to integrate both intrinsic bone quality properties from nano-indentation and microarchitecture measured by micro-computed tomography (μCT). The two groups included intact female Fischer rats fed a normal diet (controls, N = 12) or a diet containing strontium ranelate (900 mg/kg/day; N = 12) for a period of 104 weeks. The L 5 vertebra was scanned by μCT and a morphological analysis of the vertebral body was performed. Subsequently, those μCT data were the basis of FE models with added virtual endcaps that simulated axial compression tests. The FE models were solved with the vertebral bodies only and repeated with the vertebral processes intact. In the initial stages, the intrinsic bone properties were kept constant between the control and the treated animals in order to independently study the impact of microarchitectural changes on bone strength. Morphological data indicated a significant improvement in bone microarchitecture associated with strontium ranelate compared to controls, including a 40% ( p < 0.01) higher trabecular thickness, a 28% ( p < 0.01) higher cortical thickness, and no significant change in the number of trabeculae ( p = 0.56). The poor correlation of bone strontium content against bone volume fraction (BV/TV) ( R 2 = 0.013, p = 0.74) and BMD ( R 2 = 0.153, p = 0.23) indicated that the morphological data were not biased by the presence of strontium in bone. The FE simulations demonstrated a 22% ( p < 0.01) increase of stiffness and 29% ( p < 0.01) increase in strength compared to controls. The magnitudes were greater, but the relative differences were similar when the entire intact vertebra was modeled compared to the vertebral body alone. Adjusting the FE models to account for differences in intrinsic bone tissue quality between control and treated animals resulted in an even higher bone strength with strontium ranelate. Furthermore, load transfer in strontium ranelate treated animals shifted from an equal distribution between cortical and trabecular compartments to more load being supported by the trabecular bone (a shift of 8%, p < 0.02). Tissue-level stresses were reduced on average (− 7%, p < 0.01) and more homogeneously distributed. Together, these findings indicated that, independently from bone strontium content, microarchitectural adaptations played a major role in the increased bone strength associated with strontium ranelate exposure and that the changes in load distribution resulted in patterns that were more favorable to resisting fracture.

High-Resolution Peripheral Quantitative Computed Tomographic Imaging of Cortical and Trabecular Bone Microarchitecture in Patients with Type 2 Diabetes Mellitus

Cross-sectional epidemiological studies have found that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of certain fragility fractures despite normal or elevated bone mineral density (BMD). In this study, high-resolution peripheral quantitative computed tomography was applied to characterize cortical and trabecular microarchitecture and biomechanics in the peripheral skeleton of female patients with T2DM. A cross-sectional study was conducted in patients with T2DM recruited from a diabetic outpatient clinic. Elderly female patients (age, 62.9 ± 7.7 yr) with a history of T2DM (n = 19) and age- and height-matched controls (n = 19) were recruited. Subjects were imaged using high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Quantitative measures of volumetric (BMD), cross-sectional geometry, trabecular and cortical microarchitecture were calculated. Additionally, compressive mechanical properties were determined by micro-finite element analysis. Compared to the controls, the T2DM cohort had 10% higher trabecular volumetric BMD (P < 0.05) adjacent to the cortex and higher trabecular thickness in the tibia (13.8%; P < 0.05). Cortical porosity differences alone were consistent with impaired bone strength and were significant in the radius (>+50%; P < 0.05), whereas pore volume approached significance in the tibia (+118%; P = 0.1). The results of this pilot investigation provide a potential explanation for the inability of standard BMD measures to explain the elevated fracture incidence in patients with T2DM. The findings suggest that T2DM may be associated with impaired resistance to bending loads due to inefficient redistribution of bone mass, characterized by loss of intracortical bone offset by an elevation in trabecular bone density.

Cancellous Bone Volume Is Restored By Intermittent PTH After Mechanical Unloading

PURPOSE Skeletally mature rats subjected to 28 days of hindlimb unloading (HU) experience a significant loss of proximal tibia bone mineral density (BMD) and plantar flexor muscle strength. Although muscle strength recovers within 14 days of reambulation, there is no sign of BMD recovery through 28 days. The purpose of this study was to evaluate the effectiveness of daily PTH (1–34; 80μg/kg/day) administration on enhancing recovery of bone parameters following 28 days of HU to better match rate of muscle strength recovery. METHODS Six-month-old male Sprague Dawley rats were divided into 3 groups: 28 day HU (HU; n=4), 28 day HU + 28 day recovery with vehicle (VEH; n=8) and 28 day HU + 28 day recovery with PTH (PTH; n=8). Both recovery groups received daily subcutaneous injections for 28 days during recovery from HU. In vivo peripheral quantitative computed tomography (pQCT; Stratec, Research M) scans of the proximal tibia metaphysis were obtained at baseline, after 28 days of HU (R+0), and at recovery days 14 (R+14) and 28 (R+28). In vivo peak isometric torque (ISO) and mass of plantar flexor muscles were obtained at sacrifice. RESULTS After HU (R+0), there was a significant loss of volumetric bone mineral density (vBMD) for both total (cortical shell + cancellous core) and cancellous-only compartments (−7 and 9%, respectively). At R+14, total and cancellous BMD of VEH -treated animals (544± 14 and 223 ±10 mg/cm3, respectively) remained similar to R+0 values while PTH-treated animals significantly increased both total and cancellous BMD (635 ± 17 and 257 ± 6 mg/cm3, respectively), to baseline levels. By R+28, BMD of VEH animals remained at R+0 levels while values in PTH-treated animals exceeded baseline values (+11 and 21 % for total and cancellous BMD). Muscle mass was significantly greater in both VEH and PTH groups compared to HU (+37 and 29%, respectively) while ISO was non-significantly higher (+3 and 4%, respectively). A subset of bones (n=2/gp) were analyzed using microCT (GE Medical Systems, RS-9) at the same location as studied by pQCT. PTH-treated animals had significantly higher cancellous BV/TV (+ 141%), accounted for by higher trabecular thickness (+33%) and number (+ 83%), compared to VEH-treated animals; there was no difference between HU and VEH-treated values. CONCLUSIONS These data demonstrate that mechanical unloading of bone does not preclude a robust response to PTH during subsequent reloading, and that recovery of cancellous bone volume and architecture is significantly enhanced by intermittent PTH.

OA24 Magnetic resonance imaging of the trabecular bone microarchitecture at 3 Tesla - comparison with 1.5 Tesla

Objectifs High-resolution MRI has currently evolved as a promising technique to depict trabecular bone architecture. However, one drawback is a limited spatial resolution and signal-to-noise ratio (SNR). With the advent of 3T MRI it is possible to improve spatial resolution and SNR in a clinical setting. The purpose of this study was to compare standard 1,5T MR imaging of trabecular bone structure with imaging at 3T. Materiels et methodes Ten human calcaneus specimens were imaged with a wrist coil at 1,5T (Fast Gradient Recalled Echo (FGRE) - sequence with TR = 19 ms, TE = 4,6 ms, flip angle 20°) and at 3 T (FGRE-sequence with TR = 19,6 ms, TE = 4,7 ms, flip angle 20°) using the same spatial resolution. Structural analysis was performed after an alignment procedure between MR images at 1,5 T and at 3 T. Structural parameters and SNR determined in the corresponding sections, were compared. Resultats SNR was substantially higher in the images obtained at 3T. Qualitative analysis showed a better depiction of the trabecular bone structure at 3T and the quantitative analysis demonstrated significantly higher apparent trabecular number and trabecular thickness, thus also increasing bone volume fraction. Conclusion These preliminary results show that imaging at 3T may substantially improve the depiction of trabecular bone microarchitecture though suceptibility artifacts also increase.