Contribution of Trabecular and Cortical Components to Biomechanical Behavior of Human Vertebrae: An Ex Vivo Study

Whereas there is clear evidence for a strong influence of bone quantity (i.e., bone mass or bone mineral density) on vertebral mechanical behavior, there are fewer data addressing the relative influence of cortical and trabecular bone microarchitecture. The aim of this study was to determine the relative contributions of bone mass, trabecular microarchitecture, and cortical thickness and curvature to the mechanical behavior of human lumbar vertebrae. Thirty‐one L3 vertebrae (16 men, 15 women, aged 75 ± 10 years and 76 ± 10 years, respectively) were obtained. Bone mineral density (BMD) of the vertebral body was assessed by lateral dual energy X‐ray absorptiometry (DXA), and 3D trabecular microarchitecture and anterior cortical thickness and curvature was assessed by micro‐computed tomography (µCT). Then compressive stiffness, work to failure, and failure load were measured on the whole vertebral body. BMD was correlated with compressive stiffness (r = 0.60), failure load (r = 0.70), and work to failure (r = 0.55). Except for the degree of anisotropy, all trabecular and cortical parameters were correlated with mechanical behavior (r = 0.36 to 0.58, p = .05 to .001, and r = 0.36 to 0.61, p = .05 to .0001, respectively). Stepwise and multiple regression analyses indicated that the best predictor of (1) failure load was the combination of BMD, structural model index (SMI), and trabecular thickness (Tb.Th) (R = 0.80), (2) stiffness was the combination of BMD, Tb.Th, and curvature of the anterior cortex (R = 0.82), and (3) work to failure was the combination of anterior cortical thickness and BMD (R = 0.68). Our data imply that measurements of cortical thickness and curvature may enhance prediction of vertebral fragility and that therapies that improve both vertebral cortical and trabecular bone properties may provide a greater reduction in fracture risk. © 2010 American Society for Bone and Mineral Research     

The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study

Summary

We investigated the association of trabecular bone score (TBS) with microarchitecture and mechanical behavior of human lumbar vertebrae. We found that TBS reflects vertebral trabecular microarchitecture and is an independent predictor of vertebral mechanics. However, the addition of TBS to areal BMD (aBMD) did not significantly improve prediction of vertebral strength.

Introduction

The trabecular bone score (TBS) is a gray-level measure of texture using a modified experimental variogram which can be extracted from dual-energy X-ray absorptiometry (DXA) images. The current study aimed to confirm whether TBS is associated with trabecular microarchitecture and mechanics of human lumbar vertebrae, and if its combination with BMD improves prediction of fracture risk.

Methods

Lumbar vertebrae (L3) were harvested fresh from 16 donors. The anteroposterior and lateral bone mineral content (BMC) and areal BMD (aBMD) of the vertebral body were measured using DXA; then, the TBS was extracted using TBS iNsight software (Medimaps SA, France). The trabecular bone volume (Tb.BV/tissue volume, TV), trabecular thickness (Tb.Th), degree of anisotropy, and structure model index (SMI) were measured using microcomputed tomography. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies to assess failure load and stiffness.

Results

The TBS was significantly correlated to Tb.BV/TV and SMI (r?=?0.58 and ?0.62; p?=?0.02, 0.01), but not related to BMC and BMD. TBS was significantly correlated with stiffness (r?=?0.64; p?=?0.007), independently of bone mass. Using stepwise multiple regression models, we failed to demonstrate that the combination of BMD and TBS was better at explaining mechanical behavior than either variable alone. However, the combination TBS, Tb.Th, and BMC did perform better than each parameter alone, explaining 79 % of the variability in stiffness.

Conclusions

In our study, TBS was associated with microarchitecture parameters and with vertebral mechanical behavior, but TBS did not improve prediction of vertebral biomechanical properties in addition to aBMD.     

Trabecular Bone Structure Analysis in the Osteoporotic Spine Using a Clinical In Vivo Setup for 64‐Slice MDCT Imaging: Comparison to μCT Imaging and μFE Modeling

Assessment of trabecular microarchitecture may improve estimation of biomechanical strength, but visualization of trabecular bone structure in vivo is challenging. We tested the feasibility of assessing trabecular microarchitecture in the spine using multidetector CT (MDCT) on intact human cadavers in an experimental in vivo–like setup. BMD, bone structure (e.g., bone volume/total volume = BV/TV; trabecular thickness = Tb.Th; structure model index = SMI) and bone texture parameters were evaluated in 45 lumbar vertebral bodies using MDCT (mean in‐plane pixel size, 274 μm²; slice thickness, 500 μm). These measures were correlated with structure measures assessed with μCT at an isotropic spatial resolution of 16 μm and to microfinite element models (μFE) of apparent modulus and stiffness. MDCT‐derived BMD and structure measures showed significant correlations to the density and structure obtained by μCT (BMD, R² = 0.86, p < 0.0001; BV/TV, R² = 0.64, p < 0.0001; Tb.Th, R² = 0.36, p < 0.01). When comparing μCT‐derived measures with μFE models, the following correlations (p < 0.001) were found for apparent modulus and stiffness, respectively: BMD (R² = 0.58 and 0.66), BV/TV (R² = 0.44 and 0.58), and SMI (R² = 0.44 and 0.49). However, the overall highest correlation (p < 0.001) with μFE app. modulus (R² = 0.75) and stiffness (R² = 0.76) was achieved by the combination of QCT‐derived BMD with the bone texture measure Minkowski Dimension. In summary, although still limited by its spatial resolution, trabecular bone structure assessment using MDCT is overall feasible. However, when comparing with μFE‐derived bone properties, BMD is superior compared with single parameters for microarchitecture, and correlations further improve when combining with texture measures.     

Human parathyroid hormone (1-34) increases mass and structure of the cortical shell,with resultant increase in lumbar bone strength,in ovariectomized rats

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42–84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.     

Differential Effects of Bone Mineral Content and Bone Area on Vertebral Strength in a Swine Model

Since the biomechanical competence of a vertebral body may be closely related to the content and distribution of the bone mineral, we have evaluated the effects of projected vertebral bone area (BA) and bone mineral parameters [bone mineral content (BMC) or bone mineral density (BMD)] on their biomechanical competence. We used dual-energy X-ray absorptiometry (DXA) to assess the bone mineral parameters of 36 swine thoracic vertebrae (T1–T12) and 15 lumbar vertebrae (L1–L5) after removal of the posterior elements. The failure load, compressive stress, and the stored strain energy of these vertebral bodies were assessed by a uniaxial compressive test using an MTS 810 testing system. Multiple regression analysis showed a significantly negative effect of BA and significantly positive effect of BMC on the biomechanical competence (compressive stress, r²= 0.67, P < 0.0001; failure load, r²= 0.75, P < 0.0001). However, the stored strain energy was only related to the BMC (r²= 0.35, P < 0.0001). The contributory effects of BMC and BA on the biomechanical competence were not equal. The effects of BMC was larger than BA in determining the failure load and stored strain energy, whereas the reverse was found for the compressive stress. Using the log-transformed parameters as the regressors resulted in similar results. These results suggested the differential effects of BA and BMC in determining the biomechanical competence of vertebral bodies. We recommend the use of both parameters instead of BMD alone for evaluation of the vertebral biomechanical competence. Received: 26 June 1997 / Accepted: 8 January 1998     

Determinants of the mechanical behavior of human lumbar vertebrae after simulated mild fracture

The ability of a vertebra to carry load after an initial deformation and the determinants of this postfracture load‐bearing capacity are critical but poorly understood. This study aimed to determine the mechanical behavior of vertebrae after simulated mild fracture and to identify the determinants of this postfracture behavior. Twenty‐one human L₃ vertebrae were analyzed for bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA) and for microarchitecture by micro–computed tomography (µCT). Mechanical testing was performed in two phases: initial compression of vertebra to 25% deformity, followed, after 30 minutes of relaxation, by a similar test to failure to determine postfracture behavior. We assessed (1) initial and postfracture mechanical parameters, (2) changes in mechanical parameters, (3) postfracture elastic behavior by recovery of vertebral height after relaxation, and (4) postfracture plastic behavior by residual strength and stiffness. Postfracture failure load and stiffness were 11% ± 19% and 53% ± 18% lower than initial values (p = .021 and p < .0001, respectively), with 29% to 69% of the variation in the postfracture mechanical behavior explained by the initial values. Both initial and postfracture mechanical behaviors were significantly correlated with bone mass and microarchitecture. Vertebral deformation recovery averaged 31% ± 7% and was associated with trabecular and cortical thickness (r = 0.47 and r = 0.64; p = .03 and p = .002, respectively). Residual strength and stiffness were independent of bone mass and initial mechanical behavior but were related to trabecular and cortical microarchitecture (|r| = 0.50 to 0.58; p = .02 to .006). In summary, we found marked variation in the postfracture load‐bearing capacity following simulated mild vertebral fractures. Bone microarchitecture, but not bone mass, was associated with postfracture mechanical behavior of vertebrae. © 2011 American Society for Bone and Mineral Research.     

Cortical and trabecular load sharing in the human vertebral body.

The biomechanical role of the vertebral cortical shell remains poorly understood. Using high-resolution finite element modeling of a cohort of elderly vertebrae, we found that the biomechanical role of the shell can be substantial and that the load sharing between the cortical and trabecular bone is complex. As a result, a more integrative measure of the trabecular and cortical bone should improve noninvasive assessment of fracture risk and treatments. INTRODUCTION: A fundamental but poorly understood issue in the assessment of both osteoporotic vertebral fracture risk and effects of treatment is the role of the trabecular bone and cortical shell in the load-carrying capacity of the vertebral body. MATERIALS AND METHODS: High-resolution microCT-based finite element models were developed for 13 elderly human vertebrae (age range: 54-87 years; 74.6 +/- 9.4 years), and parameter studies-with and without endplates-were performed to determine the role of the shell versus trabecular bone and the effect of model assumptions. RESULTS: Across vertebrae, whereas the average thickness of the cortical shell was only 0.38 +/- 0.06 mm, the shell mass fraction (shell mass/total bone mass)-not including the endplates-ranged from 0.21 to 0.39. The maximum load fraction taken by the shell varied from 0.38 to 0.54 across vertebrae and occurred at the narrowest section. The maximum load fraction taken by the trabecular bone varied from 0.76 to 0.89 across vertebrae and occurred near the endplates. Neither the maximum shell load fraction nor the maximum trabecular load fraction depended on any of the densitometric or morphologic properties of the vertebra, indicating the complex nature of the load sharing mechanism. The variation of the shell load-carrying capacity across vertebrae was significantly altered by the removal of endplates, although these models captured the overall trend within a vertebra. CONCLUSIONS: The biomechanical role of the thin cortical shell in the vertebral body can be substantial, being about 45% at the midtransverse section but as low as 15% close to the endplates. As a result of the complexity of load sharing, sampling of only midsection trabecular bone as a strength surrogate misses important biomechanical information. A more integrative approach that combines the structural role of both cortical and trabecular bone should improve noninvasive assessment of vertebral bone strength in vivo.     

Microarchitecture Influences Microdamage Accumulation in Human Vertebral Trabecular Bone

It has been suggested that accumulation of microdamage with age contributes to skeletal fragility. However, data on the age‐related increase in microdamage and the association between microdamage and trabecular microarchitecture in human vertebral cancellous bone are limited. We quantified microdamage in cancellous bone from human lumbar (L₂) vertebral bodies obtained from 23 donors 54–93 yr of age (8 men and 15 women). Damage was measured using histologic techniques of sequential labeling with chelating agents and was related to 3D microarchitecture, as assessed by high‐resolution μCT. There were no significant differences between sexes, although women tended to have a higher microcrack density (Cr.Dn) than men. Cr.Dn increased exponentially with age (r = 0.65, p < 0.001) and was correlated with bone volume fraction (BV/TV; r = ?0.55; p < 0.01), trabecular number (Tb.N; r = ?0.56 p = 0.008), structure model index (SMI; r = 0.59; p = 0.005), and trabecular separation (Tb.Sp; r = 0.59; p < 0.009). All architecture parameters were strongly correlated with each other and with BV/TV. Stepwise regression showed that SMI was the best predictor of microdamage, explaining 35% of the variance in Cr.Dn and 20% of the variance in diffuse damage accumulation. In addition, microcrack length was significantly greater in the highest versus lowest tertiles of SMI. In conclusion, in human vertebral cancellous bone, microdamage increases with age and is associated with low BV/TV and a rod‐like trabecular architecture.     

Influence of Early and Late Zoledronic Acid Administration on Vertebral Structure and Strength in Ovariectomized Rats

An annual infusion of zoledronic acid (ZOL) reduces fracture risk in osteoporotic patients. Previously, we showed that a single ZOL injection inhibited changes in bone microstructure and strength in rat tibiae after ovariectomy. Here, we determined the effects of a single ZOL injection as preventive and restorative treatment on the bone microstructure and strength in lumbar and caudal vertebrae of ovariectomized (OVX) rats. Twenty-nine female 35-week-old Wistar rats were divided into four groups: SHAM-OVX (n = 9), OVX (n = 5), OVX and early ZOL (n = 8), and OVX and late ZOL (n = 7). ZOL was given once (20 μg/kg body weight s.c.) at OVX in the early ZOL group and 8 weeks later in the late ZOL group; rats were killed 16 weeks after OVX. Trabecular and cortical bone microarchitecture were measured in lumbar (L3) and caudal (Cd6) vertebrae using micro-computed tomography, and compressive mechanical properties were determined in L3 vertebrae. Compared to SHAM-OVX, OVX rats had significantly lower BV/TV; SMI, Tb.N, Tb.Sp, and Conn.D tended to be deteriorated in lumbar vertebrae, while both ZOL groups did not differ from the SHAM-OVX group. Both ZOL groups had significantly higher BV/TV than OVX; the early ZOL group also had significantly lower SMI and higher Tb.Th. OVX tended to decrease mechanical properties, while early and late ZOL treatment inhibited OVX-induced degeneration. Neither OVX nor ZOL induced changes in the trabecular microarchitecture of caudal vertebrae. In summary, in adult rats a single ZOL injection inhibited OVX-induced changes in lumbar vertebral bone microarchitecture and strength.     

Histomorphometric and μCT Analysis of Bone Biopsies From Postmenopausal Osteoporotic Women Treated With Strontium Ranelate

Strontium ranelate is a new anti‐osteoporotic treatment. On bone biopsies collected from humans receiving long‐term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate. Introduction: Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans. Materials and Methods: One hundred forty‐one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1–5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1–5 yr of placebo. Results and Conclusions: Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3‐yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using μCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (?22%, p = 0.01) and trabecular separation (?16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.     

Effects of preexisting microdamage,collagen cross‐links,degree of mineralization,age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely collagen cross‐link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54–95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi‐static compression tests. Collagen cross‐link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r² = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and collagen cross‐link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as cross‐link profile, microdamage and mineralization. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:481–488, 2011     

Finite element analysis performed on radius and tibia HR‐pQCT images and fragility fractures at all sites in men

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Men's Bones (STRAMBO) cohort. In this case‐control study, areal BMD (aBMD) was measured by DXA, bone microarchitecture was assessed by high resolution (HR)‐pQCT, and finite element (µFE) analysis was based on HR‐pQCT images of distal radius and tibia. A principal component (PC) analysis (PCA) was used to study the association of synthetic PCs with fracture by computing their odds ratio (OR [95%CI]) per SD change. Specific associations with vertebral fracture (n = 100), and nonvertebral fracture (n = 85) were also computed. At both sites, areal and volumetric BMD, cortical thickness and trabecular number, separation, and distribution were significantly worse in cases than in controls, with differences ranging from ?6% to 15%. µFE‐derived stiffness and failure load were 8% to 9% lower in fractures (p < .01). No difference in load distribution was found between the two groups. After adjustment for aBMD, only differences of µFE‐derived stresses, stiffness, and failure load at the tibia remained significant (p < .05). PCA resulted in defining 4 independent PCs, explaining 83% of the total variability of bone characteristics. Nonvertebral fractures were associated with PC1, reflecting bone quantity and strength at the radius (tibia) with OR = 1.64 [1.27–2.12] (2.21 [1.60–3.04]), and with PC2, defined by trabecular microarchitecture, with OR = 1.27 [1.00–1.61]. Severe vertebral fractures were associated with PC1, with OR = 1.56 [1.16–2.09] (2.21 [1.59–3.07]), and with PC2, with OR = 1.55 [1.17–2.06] (1.45 [1.06–1.98]). In conclusion, microarchitecture and biomechanical properties derived from µFE were associated with all types of fractures in men, showing that radius and tibia mechanical properties were relatively representative of distant bone site properties. © 2011 American Society for Bone and Mineral Research.     

Dietary Restriction‐Induced Alterations in Bone Phenotype: Effects of Lifelong Versus Short‐Term Caloric Restriction on Femoral and Vertebral Bone in C57BL/6 Mice

Caloric restriction (CR) is a well‐described dietary intervention that delays the onset of aging‐associated biochemical and physiological changes, thereby extending the life span of rodents. The influence of CR on metabolism, strength, and morphology of bone has been controversially discussed in literature. Thus, the present study evaluated whether lifelong CR versus short‐term late‐onset dietary intervention differentially affects the development of senile osteoporosis in C57BL/6 mice. Two different dietary regimens with 40% food restriction were performed: lifelong CR starting in 4‐week‐old mice was maintained for 4, 20, or 74 weeks. In contrast, short‐term late‐onset CR lasting a period of 12 weeks was commenced at 48 or 68 weeks of age. Control mice were fed ad libitum (AL). Bone specimens were assessed using microcomputed tomography (μCT, femur and lumbar vertebral body) and biomechanical testing (femur). Adverse effects of CR, including reduced cortical bone mineral density (Ct.BMD) and thickness (Ct.Th), were detected to some extent in senile mice (68+12w) but in particular in cortical bone of young growing mice (4+4w), associated with reduced femoral failure force (F). However, we observed a profound capacity of bone to compensate these deleterious changes of minor nutrition with increasing age presumably via reorganization of trabecular bone. Especially in lumbar vertebrae, lifelong CR lasting 20 or 74 weeks had beneficial effects on trabecular bone mineral density (Tb.BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N). In parallel, lifelong CR groups showed reduced structure model index values compared to age‐matched controls indicating a transformation of vertebral trabecular bone microarchitecture toward a platelike geometry. This effect was not visible in senile mice after short‐term 12‐week CR. In summary, CR has differential effects on cortical and trabecular bone dependent on bone localization and starting age. Our study underlines that bone compartments possess a lifelong capability to cope with changing nutritional influences. © 2015 American Society for Bone and Mineral Research.     

Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures

Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower whole bone and trabecular bone stiffness at the radius and tibia. Our results suggest that abnormalities in trabecular plate and rod microstructure may be important mechanisms of vertebral fracture in postmenopausal women.     

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.     

Skeletal Structure in Postmenopausal Women With Osteopenia and Fractures Is Characterized by Abnormal Trabecular Plates and Cortical Thinning

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity. Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius. In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls, despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia. © 2014 American Society for Bone and Mineral Research.     

Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice.

To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (microCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness--geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The microCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific.     

The role of bone intrinsic properties measured by infrared spectroscopy in whole lumbar vertebra mechanics: Organic rather than inorganic bone matrix?

Whole bone strength is determined by bone mass, microarchitecture and intrinsic properties of the bone matrix. However, few studies have directly investigated the contribution of bone tissue material properties to whole bone strength in humans. This study assessed the role of bone matrix composition on whole lumbar vertebra mechanics. We obtained 17 fresh frozen human lumbar spines (8 W, 9 M, aged 76 ± 11 years). L3 bone mass was measured by DXA and microarchitecture by μ-CT with a 35 μm-isotropic resolution. Microarchitectural parameters were directly measured: Tb.BV/TV, SMI, Tb.Th, DA, Ct.Th, Ct.Po and radius of anterior cortical curvature. Failure load (N), stiffness (N/mm) and work to failure (N.mm) were extracted from quasi-static uniaxial compressive testing performed on L3 vertebral bodies. FTIRM analysis was performed on 2 μm-thick sections from L2 trabecular cores, with a Perkin-Elmer GXII Auto-image Microscope equipped with a wide band detector. Twenty measurements per sample were performed at 30 1 100 μm of spatial resolution. Each spectrum was collected at 4 cm^− 1 resolution and 50 scans in transmission mode. Mineral and collagen maturity, and mineralization and crystallinity index were measured. There was no association between the bone matrix characteristics and bone mass or microarchitecture. Mineral maturity, mineralization and crystallinity index were not related to whole vertebra mechanics. However, collagen maturity was positively correlated with whole vertebra failure load and stiffness (r = 0.64, p = 0.005 and r = 0.54, p = 0.025, respectively). The collagen maturity (3rd step) in combination with bone mass (i.e. BMC, 1st step) and microarchitecture (i.e. Tb.Th, 2nd step) improved the prediction of whole vertebra mechanical properties in forward stepwise multiple regression models, together explaining 71% of the variability in whole vertebra stiffness (p = 0.001). In conclusion, we demonstrated a substantial contribution of collagen maturity, but not mineralization parameters, to whole bone strength of human lumbar vertebrae that was independent of bone mass and microarchitecture.     

Quantitative ultrasound of cortical bone in the femoral neck predicts femur strength: Results of a pilot study

A significant risk of femoral neck (FN) fracture exists for men and women with an areal bone mineral density (aBMD) higher than the osteoporotic range, as measured with dual‐energy X‐ray absorptiometry (DXA). Separately measuring the cortical and trabecular FN compartments and combining the results would likely be a critical aspect of enhancing the diagnostic capabilities of a new technique. Because the cortical shell determines a large part of FN strength a novel quantitative ultrasound (QUS) technique that probes the FN cortical compartment was implemented. The sensitivity of the method to variations of FN cortical properties and FN strength was tested. Nine femurs (women, mean age 83 years) were subjected to QUS to measure the through transmission time‐of‐flight (TOF) at the FN and mechanical tests to assess strength. Quantitative computed tomography (QCT) scans were performed to enable analysis of the dependence of TOF on bone parameters. DXA was also performed for reference. An ultrasound wave propagating circumferentially in the cortical shell was measured in all specimens. Its TOF was not influenced by the properties of the trabecular compartment. Averaged TOF for nine FN measurement positions/orientations was significantly correlated to strength (R² = 0.79) and FN cortical QCT variables: total BMD (R² = 0.54); regional BMD in the inferoanterior (R² = 0.90) and superoanterior (R² = 0.57) quadrants; and moment of inertia (R² = 0.71). The results of this study demonstrate that QUS can perform a targeted measurement of the FN cortical compartment. Because the method involves mechanical guided waves, the QUS variable is related to the geometric and material properties of the cortical shell (cortical thickness, tissue elasticity, and porosity). This work opens the way to a multimodal QUS assessment of the proximal femur, combining our approach targeting the cortical shell with the existing modality sensitive to the trabecular compartment. In vivo feasibility of our approach has to be confirmed with experimental data in patients. © 2013 American Society for Bone and Mineral Research     

The Influence of High‐Impact Exercise on Cortical and Trabecular Bone Mineral Content and 3D Distribution Across the Proximal Femur in Older Men: A Randomized Controlled Unilateral Intervention

Regular exercisers have lower fracture risk, despite modest effects of exercise on bone mineral content (BMC). Exercise may produce localized cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical CT. Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localized cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualized and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty‐four men aged mean (SD) 70 (4) years exercised for 12‐months, attending 92% of prescribed sessions. In traditional regions of interest, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whereas femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; p < 0.001), with larger changes (> 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; p < 0.001), with localized changes of > 12% at the anterior femoral neck, trochanter, and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise‐induced changes were localized rather than being evenly distributed across the proximal femur. © 2015 American Society for Bone and Mineral Research.