Energy Balance and Bone Health: a Nutrient Availability Perspective.

PURPOSE OF REVIEW: Obesity is highly prevalent and is associated with bone fragility and fracture. The changing nutrient availability to bone in obesity is an important facet of bone health. The goal of this article is to summarize current knowledge on the effects of carbohydrate and dietary fat availability on bone, particularly in the context of other tissues. RECENT FINDINGS: The skeleton is a primary site for fatty acid and glucose uptake. The trafficking of carbohydrates and fats into tissues changes with weight loss and periods of weight gain. Exercise acutely influences nutrient uptake into bone and may affect nutrient partitioning to bone. Bone cells secrete hormones that signal to the brain and other tissues information about its energetic state, which may alter whole-body nutrient trafficking. There is a critical need for studies to address the changes that metabolic perturbations have on nutrient availability in bone.

Femoral neck structural properties are altered in adults with type 1 diabetes.

AIMS: To determine differences in hip geometry in adults with type 1 diabetes (T1D) compared with healthy adults without diabetes. METHODS: In this cross-sectional study, 43 adults with T1D (mean age 56 years, 84 % female, 92 % White, mean duration of diabetes of 39 years, A1c of 7.8 %) and 40 adults without diabetes (mean age 60 years, 80 % female, 77 % white) who had hip dual-energy x-ray absorptiometry (DXA) scans from previous studies were included. Areal bone mineral density (aBMD) and measures of hip structural properties at the narrow neck, intertrochanteric and femoral shaft regions of the left proximal femur were analyzed between adults with T1D and controls using linear models controlled for age, sex, and body mass index. RESULTS: There were no significant differences in DXA-based aBMD at the hip (0.769 ± 0.132 vs. 0.900 ± 0.139 g/cm2, p = 0.07) or femoral neck (0.722 ± 0.116 vs. 0.849 ± 0.114 g/cm2, p = 0.09) regions between adults with T1D and controls. When controlling for age, sex, and BMI, DXA-based aBMD at the hip (0.880 ± 0.022 vs. 0.943 ± 0.020 g/cm2, p = 0.02) and femoral neck (0.750 ± 0.021 vs. 0.812 ± 0.020 g/cm2, p = 0.02) regions were significantly lower in adults with T1D than controls. Cortical thickness was significantly lower in all three hip regions in adults with T1D than in controls (narrow-neck: 0.169 ± 0.005 vs. 0.186 ± 0.005 cm, p = 0.011; intertrochanteric: 0.388 ± 0.013 vs. 0.425 ± 0.012 cm, p = 0.017; femoral shaft: 0.529 ± 0.017 vs. 0.586 ± 0.016 cm, p = 0.006). Moreover, adults with T1D had a smaller cross-sectional area at the narrow-neck (3.06 ± 0.09 vs. 3.32 ± 0.08 cm2, p = 0.015), a higher femoral shaft endocortical diameter (2.23 ± 0.07 vs. 2.02 ± 0.06 cm, p = 0.011), and higher buckling ratios (an indicator of cortical instability) at the intertrochanteric (9.22 ± 0.34 vs. 8.23 ± 0.32, p = 0.016) and femoral shaft (3.32 ± 0.15 vs. 2.89 ± 0.14, p = 0.016) regions. CONCLUSIONS: Adults with T1D have several significant differences in proximal femur morphology compared with controls. These morphological differences may adversely affect the mechanical integrity of the proximal femur, thereby contributing to an increased risk of fracture in the event of a fall.

Effect of foam densification and impact velocity on the performance of a football helmet using computational modeling.

The NFL recently released validated helmet-impact models to study the performance of currently used helmets. This study used the model of a Riddell Speed Classic helmet to determine the influence of the properties of protective foam padding on acceleration and deformation at two common impact locations to cause concussions. The performance of the helmet was measured before and after manipulating the material properties of the protective foam liner material using FEA software. The densification strain was adjusted by using the scale factor tool in LS-DYNA to create four material categories - soft, standard, stiff, and rigid. The helmet was tested under side and rear impacts using the four material properties at 2.0, 5.5, 7.4, 9.3 and 12.3 m/s impact speeds using the NOCSAE linear impactor model. This study suggests that the standard foam material compresses to a range that could be considered to have "bottomed out" at impact speeds at 5.5 m/s for side impacts. Despite testing a wide range of material properties, the measured accelerations did not vary dramatically across material properties. Rather, impact speed played the dominant role on measured acceleration. This is the first study to demonstrate how open-source impact models can be used to run a design of experiments and investigate the role between different materials used inside a helmet and football helmet performance.

Impact of Exercise and Activity on Weight Regain and Musculoskeletal Health Post-Ovariectomy.

The purpose of this study was to determine whether obesity and/or exercise training alters weight regain and musculoskeletal health after ovariectomy (OVX). Female rats were fed high-fat diet (HFD) to reveal obesity-prone (OP) and obesity-resistant (OR) phenotypes. The OP and OR exercising (EX) and sedentary (SED) rats were calorically restricted to lose 15% of body weight using medium-fat diet. Rats were then maintained in energy balance for 8 wk before OVX. After OVX and a brief calorically limited phase, rats were allowed to eat ad libitum until body weight plateaued. Starting at weight loss, EX ran 1 h·d, 6 d·wk, 15 m·min. Energy intake, spontaneous physical activity (SPA), and total energy expenditure were evaluated at the end of weight maintenance pre-OVX, and at three time points post-OVX: before weight regain, during early regain, and after regain. Data are presented as mean ± SE. Exercise attenuated weight regain after OVX in OP only (OP-EX, 123 ± 10 g; OP-SED, 165 ± 12 g; OR-EX, 121 ± 6 g; OR-SED, 116 ± 6 g), which was primarily an attenuation of fat gain. The early post-OVX increase in energy intake explained much of the weight regain, and was similar across groups. Exercising improved bone strength, as did maintaining SPA. Group differences in muscle mitochondrial respiration were not significant. The large decrease in SPA due to OVX was persistent, but early weight regain was dependent on decreased SPA. In conclusion, leanness and exercise do not necessarily protect from OVX-induced weight gain. Exercise prevented weight gain in obese rats, but loss of SPA was the greatest contributor to post-OVX weight gain. Thus, understanding the mechanisms resulting in reduction in SPA after ovarian hormone loss is critical in the prevention of menopause-associated metabolic dysfunction.

Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice.

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD. We evaluated bone from young adult (6 mo.), middle-age (18 mo.), and old (24 mo.) male C57Bl/6 mice three months following either 5/6th nephrectomy, to induce CKD, or Sham procedures. CKD exacerbated losses of cortical and trabecular microarchitecture associated with aging. Aging and CKD each resulted in thinner, more porous cortices and fewer and thinner trabeculae. Bone material quality was also reduced with CKD, and these changes to bone material were distinct from those due to age. Aging reduced whole-bone flexural strength and modulus, micrometer-scale nanoindentation modulus, and nanometer-scale tissue and collagen strain (small-angle x-ray scattering [SAXS]. By contrast, CKD reduced work to fracture and variation in bone tissue modulus and composition (Raman spectroscopy), and increased percent collagen strain. The increased collagen strain burden was associated with loss of toughness in CKD. In addition, osteocyte lacunae became smaller, sparser, and more disordered with age for Sham mice, yet these age-related changes were not clearly observed in CKD. However, for CKD, larger lacunae positively correlated with increased serum phosphate levels, suggesting that osteocytes play a role in systemic mineral homeostasis. This work demonstrates that CKD reduces bone quality, including microarchitecture and bone material properties, and that loss of bone quality with age is compounded by CKD. These findings may help reconcile why bone mass does not consistently predict fracture in the CKD population, as well as why older individuals with CKD are at high risk of fragility.

Type 1 diabetes onset at young age is associated with compromised bone quality.

Women with type 1 diabetes (T1D) are at increased risk for fracture. We studied the association of T1D and young age at T1D onset (T1D onset before 20 years) on bone structural quality. 24 postmenopausal women with T1D (mean age 60.9 years, mean T1D duration 41.7 years) and 22 age, sex- and body mass index (BMI)-matched controls underwent dual X-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the lumbar spine, hip and distal radius. Bone mass, geometry and estimated bone strength were assessed at distal and shaft of non-dominant radius and tibia using peripheral quantitative computed tomography (pQCT). Postmenopausal women with T1D had lower trabecular volumetric bone mineral density (vBMD) (LSM ±â€¯SEM; 166.1 ±â€¯8.2 vs 195.9 ±â€¯8.3 mg/cm3, p = 0.02) and compressive bone strength (24.6 ±â€¯1.8 vs 30.1 ±â€¯1.9 mg2/mm4, p = 0.04) at the distal radius compared to controls adjusting for age, BMI and radius length. At the distal radius, patients with young onset T1D had lower total vBMD (258.7 ±â€¯19.7 vs 350.8 ±â€¯26.1 mg/cm3, p = 0.02) and trabecular vBMD (141.4 ±â€¯11.6 vs 213.6 ±â€¯15.4 mg/cm3, p = 0.003) compared to adult onset T1D patients adjusting for age, BMI and the radius length. At the tibial shaft, young onset T1D patients had larger endosteal circumference (39.1 ±â€¯1.2 vs 32.1 ±â€¯1.6 mm, p = 0.005) with similar periosteal circumference (67.1 ±â€¯0.9 vs 65.1 ±â€¯1.2 mm, p = 0.2) resulting in reduced cortical thickness (4.4 ±â€¯0.1 vs 5.2 ±â€¯0.1 mm, p = 0.004) compared to adult onset T1D patients adjusting for age, BMI and the tibia length. There was no difference in the lumbar spine, femoral neck, total hip and distal radius DXA-measured aBMD between subjects with T1D and controls. T1D is associated with lower trabecular vBMD at the distal radius. T1D onset before age 20 is associated with cortical bone size deficits at the tibial shaft.

Effects on hip stress following sacroiliac joint fixation: A finite element study.

For those patients who suffer from low back pain generated by the sacroiliac (SI) joint, fusion of the SI joint has proven to be an effective means of stabilizing it and reducing pain. Though it has shown promise, SI joint fusion raises clinical questions regarding its effect on neighboring joints such as the hip. As such, the purpose of this study was to determine the effects of SI joint fixation on the hip. A finite element spine-sacroiliac-hip (SSIH) model was developed and its functionality was verified against SI joint range of motion (ROM) and hip contact stress, respectively. The intact model was fixed in double leg stance at the distal femora, and loading was applied at the lumbar spine to simulate stance, flexion, extension, right and left lateral bending, and right and left axial rotation. Functionality was confirmed by measuring and comparing SI joint ROM and contact stress and area at the hip with data from the literature. Following verification of the intact SSIH model, both unilateral and bilateral SI joint fixation were modeled; hip contact stress and area were compared to the intact state. Average hip contact stress was ~2 MPa, with most motions resulting in changes less than 5% relative to intact; contact area changed less than 10% for any motion. Clinical significance: these results demonstrated that SI joint fixation with triangular titanium implants imparted little change in stress at the hip, which suggests that the risk of developing adjacent segment disease is likely low. Future clinical studies may be executed to confirm the results of this computational study.

New Guinea bone daggers were engineered to preserve social prestige.

Bone daggers were once widespread in New Guinea. Their purpose was both symbolic and utilitarian; they functioned as objects of artistic expression with the primary function of stabbing and killing people at close quarters. Most daggers were shaped from the tibiotarsus of cassowaries, but daggers shaped from the femora of respected men carried greater social prestige. The greater cross-sectional curvature of human bone daggers indicates superior strength, but the material properties of cassowary bone are unknown. It is, therefore, uncertain whether the macrostructure of human bone daggers exists to compensate for inferior material properties of human femora or to preserve the symbolic value of a prestigious object. To explore this question, we used computed tomography to examine the structural mechanics of 11 bone daggers, 10 of which are museum-accessioned objects of art. We found that human and cassowary bones have similar material properties and that the geometry of human bone daggers results in higher moments of inertia and a greater resistance to bending. Data from finite-element models corroborated the superior mechanical performance of human bone daggers, revealing greater resistance to larger loads with fewer failed elements. Taken together, our findings suggest that human bone daggers were engineered to preserve symbolic capital, an outcome that agrees well with the predictions of signalling theory.

Bone health in type 1 diabetes.

PURPOSE OF REVIEW: This article reviews recent publications on the effect of type 1 diabetes (T1D) on fracture risk, bone mineral density (BMD), bone structure, and bone tissue quality. Possible fracture prevention strategies for patients with T1D have also been reviewed. RECENT FINDINGS: T1D is associated with substantially elevated fracture risk and modestly low BMD at the femoral neck. However, BMD alone does not explain higher observed fracture risk in T1D. T1D also affects bone macro- and microstructure, characterized by thinner cortices and trabecular bone changes such as thinner and more widely spaced trabeculae. Structural bone deficit is pronounced in the presence of microvascular complications. Tissue-level changes, such as accumulation of advanced glycation endproducts, detrimental alterations of the mineral phase because of low bone turnover, and occlusion of vascular channels in bone by mineralized tissue, are implicated in pathophysiology of bone fragility in T1D. There are no guidelines on screening and prevention of osteoporotic fractures in T1D. SUMMARY: More studies are needed to understand the influence of T1D on structural bone quality and tissue material properties. There is a need for a prospective study to evaluate better screening strategies for diagnosis and treatment of osteoporosis in T1D.

Biological evaluation and finite-element modeling of porous poly(para-phenylene) for orthopaedic implants.

Poly(para-phenylene) (PPP) is a novel aromatic polymer with higher strength and stiffness than polyetheretherketone (PEEK), the gold standard material for polymeric load-bearing orthopaedic implants. The amorphous structure of PPP makes it relatively straightforward to manufacture different architectures, while maintaining mechanical properties. PPP is promising as a potential orthopaedic material; however, the biocompatibility and osseointegration have not been well investigated. The objective of this study was to evaluate biological and mechanical behavior of PPP, with or without porosity, in comparison to PEEK. We examined four specific constructs: 1) solid PPP, 2) solid PEEK, 3) porous PPP and 4) porous PEEK. Pre-osteoblasts (MC3T3) exhibited similar cell proliferation among the materials. Osteogenic potential was significantly increased in the porous PPP scaffold as assessed by ALP activity and calcium mineralization. In vivo osseointegration was assessed by implanting the cylindrical materials into a defect in the metaphysis region of rat tibiae. Significantly more mineral ingrowth was observed in both porous scaffolds compared to the solid scaffolds, and porous PPP had a further increase compared to porous PEEK. Additionally, porous PPP implants showed bone formation throughout the porous structure when observed via histology. A computational simulation of mechanical push-out strength showed approximately 50% higher interfacial strength in the porous PPP implants compared to the porous PEEK implants and similar stress dissipation. These data demonstrate the potential utility of PPP for orthopaedic applications and show improved osseointegration when compared to the currently available polymeric material. STATEMENT OF SIGNIFICANCE: PEEK has been widely used in orthopaedic surgery; however, the ability to utilize PEEK for advanced fabrication methods, such as 3D printing and tailored porosity, remain challenging. We present a promising new orthopaedic biomaterial, Poly(para-phenylene) (PPP), which is a novel class of aromatic polymers with higher strength and stiffness than polyetheretherketone (PEEK). PPP has exceptional mechanical strength and stiffness due to its repeating aromatic rings that provide strong anti-rotational biaryl bonds. Furthermore, PPP has an amorphous structure making it relatively easier to manufacture (via molding or solvent-casting techniques) into different geometries with and without porosity. This ability to manufacture different architectures and use different processes while maintaining mechanical properties makes PPP a very promising potential orthopaedic biomaterial which may allow for closer matching of mechanical properties between the host bone tissue while also allowing for enhanced osseointegration. In this manuscript, we look at the potential of porous and solid PPP in comparison to PEEK. We measured the mechanical properties of PPP and PEEK scaffolds, tested these scaffolds in vitro for osteocompatibility with MC3T3 cells, and then tested the osseointegration and subsequent functional integration in vivo in a metaphyseal drill hole model in rat tibia. We found that PPP permits cell adhesion, growth, and mineralization in vitro. In vivo it was found that porous PPP significantly enhanced mineralization into the construct and increased the mechanical strength required to push out the scaffold in comparison to PEEK. This is the first study to investigate the performance of PPP as an orthopaedic biomaterial in vivo. PPP is an attractive material for orthopaedic implants due to the ease of manufacturing and superior mechanical strength.

Effect of porous orthopaedic implant material and structure on load sharing with simulated bone ingrowth: A finite element analysis comparing titanium and PEEK.

Osseointegration of load-bearing orthopaedic implants, including interbody fusion devices, is critical to long-term biomechanical functionality. Mechanical loads are a key regulator of bone tissue remodeling and maintenance, and stress-shielding due to metal orthopaedic implants being much stiffer than bone has been implicated in clinical observations of long-term bone loss in tissue adjacent to implants. Porous features that accommodate bone ingrowth have improved implant fixation in the short term, but long-term retrieval studies have sometimes demonstrated limited, superficial ingrowth into the pore layer of metal implants and aseptic loosening remains a problem for a subset of patients. Polyether-ether-ketone (PEEK) is a widely used orthopaedic material with an elastic modulus more similar to bone than metals, and a manufacturing process to form porous PEEK was recently developed to allow bone ingrowth while preserving strength for load-bearing applications. To investigate the biomechanical implications of porous PEEK compared to porous metals, we analyzed finite element (FE) models of the pore structure-bone interface using two clinically available implants with high (> 60%) porosity, one being constructed from PEEK and the other from electron beam 3D-printed titanium (Ti). The objective of this study was to investigate how porous PEEK and porous Ti mechanical properties affect load sharing with bone within the porous architectures over time. Porous PEEK substantially increased the load share transferred to ingrown bone compared to porous Ti under compression (i.e. at 4 weeks: PEEK = 66%; Ti = 13%), tension (PEEK = 71%; Ti = 12%), and shear (PEEK = 68%; Ti = 9%) at all time points of simulated bone ingrowth. Applying PEEK mechanical properties to the Ti implant geometry and vice versa demonstrated that the observed increases in load sharing with PEEK were primarily due to differences in intrinsic elastic modulus and not pore architecture (i.e. 4 weeks, compression: PEEK material/Ti geometry = 53%; Ti material/PEEK geometry = 12%). Additionally, local tissue energy effective strains on bone tissue adjacent to the implant under spinal load magnitudes were over two-fold higher with porous PEEK than porous Ti (i.e. 4 weeks, compression: PEEK = 784 ± 351 microstrain; Ti = 180 ± 300 microstrain; and 12 weeks, compression: PEEK = 298 ± 88 microstrain; Ti = 121 ± 49 microstrain). The higher local strains on bone tissue in the PEEK pore structure were below previously established thresholds for bone damage but in the range necessary for physiological bone maintenance and adaptation. Placing these strain magnitudes in the context of literature on bone adaptation to mechanical loads, this study suggests that porous PEEK structures may provide a more favorable mechanical environment for bone formation and maintenance under spinal load magnitudes than currently available porous 3D-printed Ti, regardless of the level of bone ingrowth.

A new open-source tool for measuring 3D osteocyte lacunar geometries from confocal laser scanning microscopy reveals age-related changes to lacunar size and shape in cortical mouse bone.

Osteocytes can participate in systemic mineral homeostasis through perilacunar maintenance and remodeling, where changes to osteocyte lacunar morphology may affect bone structural integrity, tissue strains, and osteocyte mechanosensitivity. Though aging is associated with both decreased bone quality and altered mineral metabolism, it is not known if osteocyte lacunae undergo age-related changes in geometry. In order to survey lacunar changes with age, we developed an open-source program whereby 3D osteocyte lacunae are automatically segmented and then subsequently reconstructed from confocal laser scanning microscopy (CLSM) depth stacks for quantitative analysis of geometry and orientation. This approach takes advantage of the availability and speed of CLSM while avoiding time-consuming and bias-prone manual segmentation. Unlike conventional approaches used to quantify osteocyte lacunar morphology, CLSM enables facile analysis in three-dimensions with clear identification of osteocyte lacunae. We report that 3D osteocyte lacunae measured by CLSM become smaller, more spherical, more oblate, more spatially disorganized, and more sparsely populated with increased age in C57Bl/6 mouse cortical bone in groups spanning 6-24 months old. Critically, these age-related changes are in large part not observed in 2D analyses from the same samples. These results (1) demonstrate proof-of-concept of an efficient method to quantitatively assess osteocyte lacunae in 3D for application to a wide range of studies and (2) motivate further inquiry into how changes to osteocyte lacunar geometries and perilacunar material contribute to diminished bone quality in aging.

Ibuprofen before Exercise Does Not Prevent Cortical Bone Adaptations to Training.

Using a nonsteroidal anti-inflammatory drug (NSAID) before a single bout of mechanical loading can reduce bone formation response. It is unknown whether this translates to an attenuation of bone strength and structural adaptations to exercise training. PURPOSE: This study aimed to determine whether nonsteroidal anti-inflammatory drug use before exercise prevents increases in bone structure and strength in response to weight-bearing exercise. METHODS: Adult female Wistar rats (n = 43) were randomized to ibuprofen (IBU) or vehicle (VEH) and exercise (EX) or sedentary (SED) groups in a 2 × 2 (drug and activity) ANCOVA design with body weight as the covariate, and data are reported as mean ± SE. IBU drops (30 mg·kg BW) or VEH (volume equivalent) were administered orally 1 h before the bout of exercise. Treadmill running occurred 5 d·wk for 60 min·d at 20 m·min with a 5° incline for 12 wk. Micro-CT, mechanical testing, and finite element modeling were used to quantify bone characteristics. RESULTS: Drug-activity interactions were not significant. Exercise increased tibia cortical cross-sectional area (EX = 5.67 ± 0.10, SED = 5.37 ± 0.10 mm, P < 0.01) and structural estimates of bone strength (Imax: EX = 5.16 ± 0.18, SED = 4.70 ± 0.18 mm, P < 0.01; SecModPolar: EX = 4.01 ± 0.11, SED = 3.74 ± 0.10 mm, P < 0.01). EX had increased failure load (EX = 243 ± 9, SED = 202 ± 7 N, P < 0.05) and decreased distortion in response to a 200-N load (von Mises stress at tibia-fibula junction: EX = 48.2 ± 1.3, SED = 51.7 ± 1.2 MPa, P = 0.01). There was no effect of ibuprofen on any measurement tested. Femur results revealed similar patterns. CONCLUSION: Ibuprofen before exercise did not prevent the skeletal benefits of exercise in female rats. However, exercise that engenders higher bone strains may be required to detect an effect of ibuprofen.

An evolutionary model of osteoarthritis including articular cartilage damage, and bone remodeling in a computational study.

With osteoarthritis, a complex set of progressive chemical, biological, and mechanical changes occur in both cartilage and bone. The aim of this study is to develop a high-fidelity computational model of the complete bone-cartilage unit to study the evolution of osterarthritis-induced articular cartilage (AC) damage and remodeling of subchondral cortical bone (SCB) and subchondral trabecular bone (STB). A finite element model of spherical indentation was developed with a depth-dependent anisotropic model of degenerating articular cartilage, a calcified cartilage (CC) zone, and SCB and STB remodeling regions. Calcified tissue (CC, SCB, and STB) and AC material regions were integrated to form an evolutionary bone-cartilage unit model. Results indicate that with indentation loading, articular cartilage damage occurs at the articular surface. Furthermore, bone remodeling was predicted to occur with a net stiffening of the subchondral bone plate. Changes in indentation force were minimal (<2%) between initial and final peak indentation loading. However, additional degradation and wear of AC and/or alterations in loading may have more pronounced effects on the mechanical response of the bone-cartilage unit. Bone remodeling and articular cartilage damage predictions are consistent with experimental observations that cartilage damage begins at the articular surface and subchondral bone experiences a thickening (i.e., stiffening) response with osteoarthritis. Our results provide insight into the early-term initiation behavior of osteoarthritis; the potential consequences of evolutions in AC, SCB, and STB with disease progression; and may guide future experimental and computational studies to elucidate mechanisms of osteoarthritis progression.

Finite element analysis of a pseudoelastic compression-generating intramedullary ankle arthrodesis nail.

Tibio-talo-calcaneal (TTC) arthrodesis is an end-stage treatment for patients with severe degeneration of the ankle joint. This treatment consists of using an intramedullary nail (IM) to fuse the calcaneus, talus, and tibia bones together into one construct. Poor bone quality within the joint prior to surgery is common and thus the procedure has shown complications due to non-union. However, a new FDA-approved IM nail has been released that houses a nickel titanium (NiTi) rod that uses its inherent pseudoelastic material properties to apply active compression across the fusion site. Finite element analysis was performed to model the mechanical response of the NiTi within the device. A bone model was then developed based on a quantitative computed tomography (QCT) image for anatomical geometry and bone material properties. A total bone and device system was modeled to investigate the effect of bone quality change and gather load-sharing properties during gait loading. It was found that during the highest magnitude loading of gait, the load taken by the bone was more than 50% higher than the load taken by the nail. When comparing the load distribution during gait, results from this study would suggest that the device helps to prevent stress shielding by allowing a more even distribution of load between bone and nail. In conditions where bone quality may vary patient-to-patient, the model indicates that a 10% decrease in overall bone modulus (i.e. material stiffness) due to reduced bone mineral density would result in higher stresses in the nail (3.4%) and a marginal decrease in stress for the bone (0.5%). The finite element model presented in this study can be used as a quantitative tool to further understand the stress environment of both bone and device for a TTC fusion. Furthermore, the methodology presented gives insight on how to computationally program and use the unique material properties of NiTi in an active compression state useful for bone fracture healing or fusion treatments.

The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues.

Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading.

Inter-scanner differences in in vivo QCT measurements of the density and strength of the proximal femur remain after correction with anthropomorphic standardization phantoms.

In multicenter studies and longitudinal studies that use two or more different quantitative computed tomography (QCT) imaging systems, anthropomorphic standardization phantoms (ASPs) are used to correct inter-scanner differences and allow pooling of data. In this study, in vivo imaging of 20 women on two imaging systems was used to evaluate inter-scanner differences in hip integral BMD (iBMD), trabecular BMD (tBMD), cortical BMD (cBMD), femoral neck yield moment (My) and yield force (Fy), and finite-element derived strength of the femur under stance (FEstance) and fall (FEfall) loading. Six different ASPs were used to derive inter-scanner correction equations. Significant (p<0.05) inter-scanner differences were detected in all measurements except My and FEfall, and no ASP-based correction was able to reduce inter-scanner variability to corresponding levels of intra-scanner precision. Inter-scanner variability was considerably higher than intra-scanner precision, even in cases where the mean inter-scanner difference was statistically insignificant. A significant (p<0.01) effect of body size on inter-scanner differences in BMD was detected, demonstrating a need to address the effects of body size on QCT measurements. The results of this study show that significant inter-scanner differences in QCT-based measurements of BMD and bone strength can remain even when using an ASP.

Finite element analysis of the hip and spine based on quantitative computed tomography.

Quantitative computed tomography (QCT) provides three-dimensional information about bone geometry and the spatial distribution of bone mineral. Images obtained with QCT can be used to create finite element models, which offer the ability to analyze bone strength and the distribution of mechanical stress and physical deformation. This approach can be used to investigate different mechanical loading scenarios (stance and fall configurations at the hip, for example) and to estimate whole bone strength and the relative mechanical contributions of the cortical and trabecular bone compartments. Finite element analyses based on QCT images of the hip and spine have been used to provide important insights into the biomechanical effects of factors such as age, sex, bone loss, pharmaceuticals, and mechanical loading at sites of high clinical importance. Thus, this analysis approach has become an important tool in the study of the etiology and treatment of osteoporosis at the hip and spine.

Three-dimensional in vivo patellofemoral kinematics and contact area of anterior cruciate ligament-deficient and -reconstructed subjects using magnetic resonance imaging.

PURPOSE: The purpose of this study was to test whether (1) the 3-dimensional in vivo patellofemoral kinematics and patellofemoral contact area of anterior cruciate ligament (ACL)-deficient knees are different from those of normal, contralateral knees and (2) ACL reconstruction restores in vivo patellofemoral kinematics and contact area. METHODS: Ten ACL-deficient knees and twelve ACL-reconstructed knees, as well as the contralateral uninjured knees, were tested. Magnetic resonance imaging was performed at full extension and 40 degrees of flexion under simulated partial weight-bearing conditions. Six-degrees of freedom patellofemoral kinematics, patellofemoral contact area, and contact location were analyzed by use of magnetic resonance image-based 3-dimensional patellofemoral knee models. RESULTS: The patella in the ACL-deficient knees underwent significantly more lateral tilt during flexion (P < .05) and tended to translate more laterally (P = .083) than the patella in contralateral knees. After ACL reconstruction, no kinematic parameters were significantly different from those in contralateral knees. The patellofemoral contact areas of ACL-deficient knees at both the extended and flexed positions (37 +/- 22 mm(2) and 357 +/- 53 mm(2), respectively) were significantly smaller than those of contralateral knees (78 +/- 45 mm(2) and 437 +/- 119 mm(2), respectively) (P < .05). After reconstruction, the patellofemoral contact area of ACL-reconstructed knees in the extended position (86 +/- 41 mm(2)) was significantly larger (P < .05) than that of contralateral knees (50 +/- 34 mm(2)), but no difference was detected in the flexed position. Reproducibility of all patellofemoral kinematic parameters, contact centroid translation, and contact area showed coefficients of variation of less than 6.8%. CONCLUSIONS: ACL injuries alter patellofemoral kinematics including patellar tilt and patellar lateral translation, but ACL reconstruction with hamstring or allograft restores altered patellar tilt. ACL injuries reduce the patellofemoral contact area at both the extended and flexed positions, but ACL reconstruction enlarges the patellofemoral contact area at extension and restores the normal contact area at low angles of flexion. LEVEL OF EVIDENCE: Level III, case-control study.

Quantitative computed tomography reveals the effects of race and sex on bone size and trabecular and cortical bone density.

To examine the effects of race and sex on bone density and geometry at specific sites within the proximal femur and lumbar spine, we used quantitative computed tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men, 30 CA women, and 17 AA women aged 35-45 yr. Volumetric integral bone mineral density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric cortical BMD (cBMD) was also measured in the femur regions of interest. Differences were ascertained using a multivariate regression model. Overall, AA subjects had denser bones than CA subjects, but there were no racial differences in bone size. Men had larger femoral necks but not larger vertebrae than women. The AA men had higher tBMD and cBMD in the femur than CA men, whereas AA women had higher femoral tBMD but not higher femoral cBMD than CA women. These data support the idea that higher hip fracture rates in women compared with men are associated with smaller bone size. Lower fracture rates in AA elderly compared with CA elderly are consistent with higher peak bone density, particularly in the trabecular compartment, and potentially lower rates of age-related bone loss rather than larger bone size.