Vee San Cheong

Assessments of 3D geometry, bone density distribution and bone strength improve hip fracture risk prediction but currently require the use of computed tomography (CT). 2D-to-3D statistical shape and appearance model (SSAM) reconstructions from dual-energy X-ray absorptiometry (DXA) projections have been proposed as surrogates for CT-based models. Several studies have used 3D-DXAs reconstructed by 3D-Shaper’s software method, but no study has independently cross-validated 3D-DXAs on in vivo clinical images. The first aim of this study was to evaluate the extent 3D-DXA is applicable across a diverse population. 120 paired DXA and CT images from three ethnicities (age: 20–85; aBMD:0.611–1.214 g/cm ² ) were analysed for differences in bone volume (BV), bone mineral content, vertex-to-surface distance, volumetric bone mineral density (vBMD) distribution and predicted bone strength. No subject or parameter groups showed outlier behaviour, as correlations for all results were above R ² > 0.76. However, differences were observed for volumetric measurements (BV: slope = 0.89, bias = 9.73 cm ³ ; vBMD: slope = 0.88, bias = 6.27 g/cm ³ ) and bone strength. To improve the performance, we introduced an image-processing pipeline (named as 3D-DXA*) that calibrated the linear-regression slopes and intercepts for BV, total vBMD and the minimum fall strength (N = 96). Validation results (N = 24) in 11 fall orientations showed successful correction of proportional bias to unitary slope and zero intercept (before: slopes = 0.62–0.79, bias = 0.44–0.86 kN; after: slopes = 0.88–1.03, bias = 0.12–0.70 kN). However, Pearson correlations degraded by 0.01–0.02 for 2 cases and prediction scatter (RMSE) expanded by 3–29% for 10 fall orientations. Sub-analysis showed 3D-DXA* reduced differences in vBMD distribution with the CT models, but cohort-specific differences remained. This is the first study to independently evaluate 3D-DXAs on multi-ethnic data across a wide age, including previously unstudied cohorts, and more than doubling the number of subjects used in prior validation works. These results provide detailed insights into the accuracy and limitations of DXA-based 3D reconstruction methods.

Understanding how bone adapts to external forces is fundamental for exploring potential biomechanical interventions against skeletal diseases. This can be studied preclinically, combining in vivo experiments in rodents and in silico mechanoregulation models. While the in vivo tibial loading model is widely used to study bone adaptation, the common assumption of purely axial loading may be a simplification. This study quantifies the effect of the loading direction on the strain energy density (SED) distribution in the mouse tibia, a commonly used input for mechanoregulated bone remodelling models. To achieve this, validated micro-finite element (micro-FE) models were used to test the differences in local SED when the bone was loaded along different loading directions. In vivo micro-computed tomography (micro-CT) images were acquired from the tibiae of eleven ovariectomised mice at 18 weeks old before intervention and at 20 weeks old, after six mice underwent external mechanical loading. Micro-CT-based micro-FE models were generated for each tibia at both time points and loaded with a unit load in each Cartesian direction independently. The results from these unit load models were linearly combined to simulate various loading directions, defined by angles θ (inferior-superior) and ϕ (anterior–posterior). The results revealed a high sensitivity of the mouse tibia to the loading direction across both groups and time points. Several loading directions (e.g., θ = 10 ° , ϕ = 205–210 ° ) resulted in lower medians of the top 5% SED values compared to those obtained for the nominal axial case ( θ = 0 ° , ϕ = 0 ° ). Conversely, higher values were observed for other directions (e.g., θ = 30 ° , ϕ = 35–50 ° ). These findings emphasise the importance of considering the loading direction in experimental and computational bone adaptation studies.

Few studies have investigated the effect of a monosaturated diet high in ω-9 on osteoporosis. We hypothesized that omega-9 (ω-9) protects ovariectomized (OVX) mice from a decline in bone microarchitecture, tissue loss, and mechanical strength, thereby serving as a modifiable dietary intervention against osteoporotic deterioration. Female C57BL/6J mice were assigned to sham-ovariectomy, ovariectomy, or ovariectomy + estradiol treatment prior to switching their feed to a diet high in ω-9 for 12 weeks. Tibiae were evaluated using DMA, 3-point-bending, histomorphometry, and microCT. A significant decrease in lean mass (p = 0.05), tibial area (p = 0.009), and cross-sectional moment of inertia (p = 0.028) was measured in OVX mice compared to the control. A trend was seen where OVX bone displayed increased elastic modulus, ductility, storage modulus, and loss modulus, suggesting the ω-9 diet paradoxically increased both stiffness and viscosity. This implies beneficial alterations on the macro-structural, and micro-tissue level in OVX bone, potentially decreasing the fracture risk. Supporting this, no significant differences in ultimate, fracture, and yield stresses were measured. A diet high in ω-9 did not prevent microarchitectural deterioration, nevertheless, healthy tibial strength and resistance to fracture was maintained via mechanisms independent of bone structure/shape. Further investigation of ω-9 as a therapeutic in osteoporosis is warranted.

The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9. Male C57BL/6J mice were fed either a control diet, 50:50 mix (saturated:unsaturated) high in ω-9 (HFD^50:50), a diet high in saturated fat (HSF) or a polyunsaturated fat diet high in ω-6 (PUFA) over an 8-week duration. Tibiae were retrieved and evaluated using DMA, 3-point-bending, histomorphometry, and microCT. Mice fed a HSF diet displayed key features characteristic of osteoporosis. The loss tangent was significantly increased in the HFD^50:50 diet group compared with control (p = 0.016) and PUFA-fed animals (p = 0.049). HFD^50:50-fed mice presented with an increased viscous component, longer tibiae, increased loss modulus (p = 0.009), and ultimate stress, smaller microcracks (p < 0.001), and increased trabecular width (p = 0.002) compared with control animals. A diet high in ω-9 resulted in an overall superior bone response and further analysis of its role in bone health is warranted.

The in vivo mouse tibial loading model is used to evaluate the effectiveness of mechanical loading treatment against skeletal diseases. Although studies have correlated bone adaptation with the induced mechanical stimulus, predictions of bone remodeling remained poor, and the interaction between external and physiological loading in engendering bone changes have not been determined. The aim of this study was to determine the effect of passive mechanical loading on the strain distribution in the mouse tibia and its predictions of bone adaptation. Longitudinal micro-computed tomography (micro-CT) imaging was performed over 2 weeks of cyclic loading from weeks 18 to 22 of age, to quantify the shape change, remodeling, and changes in densitometric properties. Micro-CT based finite element analysis coupled with an optimization algorithm for bone remodeling was used to predict bone adaptation under physiological loads, nominal 12N axial load and combined nominal 12N axial load superimposed to the physiological load. The results showed that despite large differences in the strain energy density magnitudes and distributions across the tibial length, the overall accuracy of the model and the spatial match were similar for all evaluated loading conditions. Predictions of densitometric properties were most similar to the experimental data for combined loading, followed closely by physiological loading conditions, despite no significant difference between these two predicted groups. However, all predicted densitometric properties were significantly different for the 12N and the combined loading conditions. The results suggest that computational modeling of bone’s adaptive response to passive mechanical loading should include the contribution of daily physiological load.

Additive manufactured, porous bone implants have the potential to improve osseointegration and reduce failure rates of orthopaedic devices. Substantially porous implants are increasingly used in a number of orthopaedic applications. HA plasma spraying–a line of sight process—cannot coat the inner surfaces of substantially porous structures, whereas electrochemical deposition of calcium phosphate can fully coat the inner surfaces of porous implants for improved bioactivity, but the osseous response of different types of hydroxyapatite (HA) coatings with ionic substitutions has not been evaluated for implants in the same in vivo model. In this study, laser sintered Ti6Al4V implants with pore sizes of Ø 700 μm and Ø 1500 μm were electrochemically coated with HA, silicon-substituted HA (SiHA), and strontium-substituted HA (SrHA), and implanted in ovine femoral condylar defects. Implants were retrieved after 6 weeks and histological and histomorphometric evaluation were compared to electrochemically coated implants with uncoated and HA plasma sprayed controls. The HA, SiHA and SrHA coatings had Ca:P, Ca:(P+Si) and (Ca+Sr):P ratios of 1.53, 1.14 and 1.32 respectively. Electrochemically coated implants significantly promoted bone attachment to the implant surfaces of the inner pores and displayed improved osseointegration compared to uncoated scaffolds for both pore sizes (p<0.001), whereas bone ingrowth was restricted to the surface for HA plasma coated or uncoated implants. Electrochemically coated HA implants achieved the highest osseointegration, followed by SrHA coated implants, and both coatings exhibited significantly more bone growth than plasma sprayed groups (p≤0.01 for all 4 cases). SiHA had significantly more osseointegration when compared against the uncoated control, but no significant difference compared with other coatings. There was no significant difference in ingrowth or osseointegration between pore sizes, and the bone-implant-contact was significantly higher in the electrochemical HA than in SiHA or SrHA. These results suggest that osseointegration is insensitive to pore size, whereas surface modification through the presence of an osteoconductive coating plays an important role in improving osseointegration, which may be critically important for extensively porous implants.