The contribution of lower-mineralized tissue to the healing of distal radius fractures assessed using HR-pQCT.

High-resolution peripheral quantitative CT (HR-pQCT) enables quantitative assessment of distal radius fracture healing. In previous studies, lower-mineralized tissue formation was observed on HR-pQCT scans, starting early during healing, but the contribution of this tissue to the stiffness of distal radius fractures is unknown. Therefore, the aim of this study was to investigate the contribution of lower-mineralized tissue to the stiffness of fractured distal radii during the first twelve weeks of healing. We did so by combining the results from two series of micro-finite element (µFE-) models obtained using different density thresholds for bone segmentation. Forty-five postmenopausal women with a conservatively-treated distal radius fracture had HR-pQCT scans of their fractured radius at baseline (BL; 1-2 weeks post-fracture), 3-4 weeks, 6-8 weeks, and 12 weeks post-fracture. Compression stiffness (S) was computed using two series of µFE-models from the scans: one series (Msingle) included only higher-mineralized tissue (>320 mg HA/cm3), and one series (Mdual) differentiated between lower-mineralized tissue (200-320 mg HA/cm3) and higher-mineralized tissue. µFE-elements were assigned a Young's Modulus of 10 GPa (higher-mineralized tissue) or 5 GPa (lower-mineralized tissue), and an axial compression test to 1 % strain was simulated. The contribution of the lower-mineralized tissue to S was quantified as the ratio Sdual/Ssingle. Changes during healing were quantified using linear mixed effects models and expressed as estimated marginal means (EMMs) with 95 %-confidence intervals (95 %-CI). Median time to cast removal was 5.0 (IQR: 1.1) weeks. Sdual and Ssingle gradually increased during healing to a significantly higher value than BL at 12 weeks post-fracture (both p < 0.0001). In contrast, Sdual/Ssingle was significantly higher than BL at 3-4 weeks post-fracture (p = 0.0010), remained significantly higher at 6-8 weeks post-fracture (p < 0.0001), and then decreased to BL-values at the 12-week visit. EMMs ranged between 1.05 (95 %-CI: 1.04-1.06) and 1.08 (95 %-CI: 1.07-1.10). To conclude, combining stiffness results from two series of µFE-models obtained using single- and dual-threshold segmentation enables quantification of the contribution of lower-mineralized tissue to the stiffness of distal radius fractures during healing. This contribution is minor but changes significantly around the time of cast removal. Its course and timing during healing may be clinically relevant. Quantification of the contribution of lower-mineralized tissue to stiffness gives a more complete impression of strength recovery post-fracture than the evaluation of stiffness using a single series of µFE-models.

The Effect of Bolus Vitamin D3 Supplementation on Distal Radius Fracture Healing: A Randomized Controlled Trial Using HR-pQCT.

Vitamin D is an important factor in bone metabolism. Animal studies have shown a positive effect of vitamin D3 supplementation on fracture healing, but evidence from clinical trials is inconclusive. A randomized controlled trial was performed to assess the effects of vitamin D3 supplementation on fracture healing using HR-pQCT-based outcome parameters. Thirty-two postmenopausal women with a conservatively treated distal radius fracture were included within 2 weeks postfracture and randomized to a low-dose (N = 10) and a high-dose (N = 11) vitamin D intervention group receiving a 6-week bolus dose, equivalent to 700 and 1800 IU vitamin D3 supplementation per day, respectively, in addition to a control group (N = 11) receiving no supplementation. After the baseline visit 1-2 weeks postfracture, follow-up visits were scheduled at 3-4, 6-8, and 12 weeks postfracture. At each visit, HR-pQCT scans of the fractured radius were performed. Cortical and trabecular bone density and microarchitectural parameters and microfinite element analysis-derived torsion, compression, and bending stiffness were assessed. Additionally, serum markers of bone resorption (CTX) and bone formation (PINP) were measured. Baseline serum levels of 25OHD3 were <50 nmol/L in 33% of all participants and <75 nmol/L in 70%. Compared with the control group, high-dose vitamin D3 supplementation resulted in a decreased trabecular number (regression coefficient ß: -0.22; p < 0.01) and lower compression stiffness (B: -3.63; p < 0.05, together with an increase in the bone resorption marker CTX (B: 0.062; p < 0.05). No statistically significant differences were observed between the control and low-dose intervention group. In conclusion, the bolus equivalent of 700 U/day vitamin D3 supplementation in a Western postmenopausal population does not improve distal radius fracture healing and an equivalent dose of 1800 IU/day may be detrimental in restoring bone stiffness during the first 12 weeks of fracture healing. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Risk factors of non-union in intramedullary stabilized diaphyseal long bone fractures: identifying the role of fracture stabilization strategies and concomitant injuries.

PURPOSE: Concomitant chest injury is known to negatively affect bone metabolism and fracture healing, whereas traumatic brain injury (TBI) appears to have positive effects on bone metabolism. Osteogenesis can also be influenced by the timing of fracture stabilization. We aimed to identify how chest injuries, TBI and fracture stabilization strategy influences the incidence of non-union. METHODS: Patients with long bone fractures of the lower extremities who had been treated between 2004 and 2014 were retrospectively analysed. Non-union was defined as fracture healing not occurring in the expected time period and in which neither progression of healing nor successful union is expected without intervention. Diverse clinical and radiological parameters were statistically analysed using the Statistical Package for the Social Sciences (SPSS). RESULTS: The total number of operations before consolidation was an independent predictor (odds ratio [OR] = 6.416, p < 0.001) for the development of non-union in patients with long bone fractures. More specifically, patients treated according to the damage control orthopaedics (DCO) principle had a significantly higher risk of developing a non-union than patients treated according to the early total care (ETC) principle (OR = 7.878, p = 0.005). Concomitant chest injury and TBI could not be identified as influencing factors for non-union development. CONCLUSION: Our results indicate that the number of operations performed in patients with long bone fractures should be kept as low as possible and that the indication for and the timing of DCO treatment should be meticulously noted to minimize the risk of non-union development.

Cortical thinning and accumulation of large cortical pores in the tibia reflect local structural deterioration of the femoral neck.

INTRODUCTION: Cortical bone thinning and a rarefaction of the trabecular architecture represent possible causes of increased femoral neck (FN) fracture risk. Due to X-ray exposure limits, the bone microstructure is rarely measurable in the FN of subjects but can be assessed at the tibia. Here, we studied whether changes of the tibial cortical microstructure, which were previously reported to be associated with femur strength, are also associated with structural deteriorations of the femoral neck. METHODS: The cortical and trabecular architectures in the FN of 19 humans were analyzed ex vivo on 3D microcomputed tomography images with 30.3 µm voxel size. Cortical thickness (Ct.Thtibia), porosity (Ct.Potibia) and pore size distribution in the tibiae of the same subjects were measured using scanning acoustic microscopy (12 µm pixel size). Femur strength during sideways falls was simulated with homogenized voxel finite element models. RESULTS: Femur strength was associated with the total (vBMDtot; R2 = 0.23, p < 0.01) and trabecular (vBMDtrab; R2 = 0.26, p < 0.01) volumetric bone mineral density (vBMD), with the cortical thickness (Ct.ThFN; R2 = 0.29, p < 0.001) and with the trabecular bone volume fraction (Tb.BV/TVFN; R2 = 0.34, p < 0.001), separation (Tb.SpFN; R2 = 0.25, p < 0.01) and number (Tb.NFN; R2 = 0.32, p < 0.001) of the femoral neck. Moreover, smaller Ct.Thtibia was associated with smaller Ct.ThFN (R2 = 0.31, p < 0.05), lower Tb.BV/TVFN (R2 = 0.29, p < 0.05), higher Tb.SpFN (R2 = 0.33, p < 0.05) and lower Tb.NFN (R2 = 0.42, p < 0.01). A higher prevalence of pores with diameter > 100 µm in tibial cortical bone (relCt.Po100µm-tibia) indicated higher Tb.SpFN (R2 = 0.36, p < 0.01) and lower Tb.NFN (R2 = 0.45, p < 0.01). CONCLUSION: Bone resorption and structural decline of the femoral neck may be identified in vivo by measuring cortical bone thickness and large pores in the tibia.

Femur strength predictions by nonlinear homogenized voxel finite element models reflect the microarchitecture of the femoral neck.

In the human femoral neck, the contribution of the cortical and trabecular architecture to mechanical strength is known to depend on the load direction. In this work, we investigate if QCT-derived homogenized voxel finite element (hvFE) simulations of varying hip loading conditions can be used to study the architecture of the femoral neck. The strength of 19 pairs of human femora was measured ex vivo using nonlinear hvFE models derived from high-resolution peripheral QCT scans (voxel size: 30.3 µm). Standing and side-backwards falling loads were modeled. Quasi-static mechanical tests were performed on 20 bones for comparison. Associations of femur strength with volumetric bone mineral density (vBMD) or microstructural parameters of the femoral neck obtained from high-resolution QCT were compared between mechanical tests and simulations and between standing and falling loads. Proximal femur strength predictions by hvFE models were positively associated with the vBMD of the femoral neck (R² > 0.61, p < 0.001), as well as with its cortical thickness (R² > 0.27, p < 0.001), trabecular bone volume fraction (R² = 0.42, p < 0.001) and with the first two principal components of the femoral neck architecture (R² > 0.38, p < 0.001). Associations between femur strength and femoral neck microarchitecture were stronger for one-legged standing than for side-backwards falling. For both loading directions, associations between structural parameters and femur strength from hvFE models were in good agreement with those from mechanical tests. This suggests that hvFE models can reflect the load-direction-specific contribution of the femoral neck microarchitecture to femur strength.

Correction: Large cortical bone pores in the tibia are associated with proximal femur strength.

[This corrects the article DOI: 10.1371/journal.pone.0215405.].

Large cortical bone pores in the tibia are associated with proximal femur strength.

Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 µm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 µm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.

BMD-based assessment of local porosity in human femoral cortical bone.

Cortical pores are determinants of the elastic properties and of the ultimate strength of bone tissue. An increase of the overall cortical porosity (Ct.Po) as well as the local coalescence of large pores cause an impairment of the mechanical competence of bone. Therefore, Ct.Po represents a relevant target for identifying patients with high fracture risk. However, given their small size, the in vivo imaging of cortical pores remains challenging. The advent of modern high-resolution peripheral quantitative computed tomography (HR-pQCT) triggered new methods for the clinical assessment of Ct.Po at the peripheral skeleton, either by pore segmentation or by exploiting local bone mineral density (BMD). In this work, we compared BMD-based Ct.Po estimates with high-resolution reference values measured by scanning acoustic microscopy. A calibration rule to estimate local Ct.Po from BMD as assessed by HR-pQCT was derived experimentally. Within areas of interest smaller than 0.5 mm2, our model was able to estimate the local Ct.Po with an error of 3.4%. The incorporation of the BMD inhomogeneity and of one parameter from the BMD distribution of the entire scan volume led to a relative reduction of the estimate error of 30%, if compared to an estimate based on the average BMD. When applied to the assessment of Ct.Po within entire cortical bone cross-sections, the proposed BMD-based method had better accuracy than measurements performed with a conventional threshold-based approach.

Fracture Repair in the Distal Radius in Postmenopausal Women: A Follow-Up 2 Years Postfracture Using HRpQCT.

Fracture healing is characterized by an intense increase in modeling and remodeling of bone, which allows removal of the cast after a stable distal radius fracture within 3 to 5 weeks. However, at that time, bone strength has not recovered yet. We studied the changes in bone mineral density (BMD), microarchitecture, and bone stiffness after a distal radius fracture during a 2-year follow-up in comparison to the contralateral side and the association between the 2-year stiffness and baseline BMD, microarchitecture, and early changes in these parameters. The fractured side of 14 postmenopausal women (mean age 64 ± 8 years) with a conservatively treated distal radius fracture was scanned by high-resolution peripheral quantitative computed tomography (HRpQCT) at 1 to 2, 3 to 4, 6 to 8, and 12 weeks and 2 years postfracture. The same region contralaterally was scanned as well at the 2-year visit. BMD, microarchitecture, and stiffness parameters were determined and the fracture side was compared with the contralateral side using a linear mixed-effect model. Spearman's correlation was used to correlate the 2-year bone stiffness with baseline BMD, microarchitecture, and early 3-month changes in these parameters. Two years postfracture, cortical and trabecular thickness and torsional and bending stiffness were significantly higher at the fractured side compared with the nonfractured side (21%, 55%, 31%, and 29%, respectively, p < 0.05), whereas BMD was similar. Two-year torsional and bending stiffness correlated significantly with baseline BMD and cortical perimeter (|rho| ≥ 0.63, p < 0.016) but not with early changes in bone parameters. Using HRpQCT, this study illustrates that fracture healing is not completed by the time the cast is removed. We showed that from 6 weeks to 2 years postfracture, large changes occur in BMD, microarchitecture, and biomechanical parameters at the fractured side, which were fully recovered after 2 years in comparison to the nonfractured contralateral side. Interestingly, higher 2-year torsional and bending stiffness were associated with lower BMD and higher cortical perimeter at baseline. © 2015 American Society for Bone and Mineral Research.