Vertebral Compressive Strength Research Articles

Benefits of Targeted Vibration for Bone Strength and Bone Density in Postmenopausal Women with Osteopenia: A Randomized, Sham-Controlled Trial

Abstract Postmenopausal women are at increased risk of fractures due to higher bone turnover that accompanies reduced estrogen production. Vibration may be an effective intervention for maintaining bone strength and bone density. The Osteoboost Belt is a wearable, home-use device that delivers targeted vibration to the lumbar spine and hips. This randomized, sham-controlled trial evaluated the safety and effectiveness of targeted vibration on bone strength and density in postmenopausal women with osteopenia. Participants (n = 126) were randomized (1:1) to receive the Active (vibration therapy device) or Sham (inactive device) treatment for 30 minutes/day over 12 months. At baseline and 12 months, computed tomography scans of the lumbar spine were analyzed to measure finite element analysis-assessed vertebral bone compressive strength (vertebral strength) and volumetric bone mineral density (vBMD) of the L1 vertebra. The primary endpoint, the difference in percentage change of vertebral strength between the Active (-1.40%, [95% CI: -2.73, -0.08]) and Sham (-2.74% [-4.04, -1.43]) groups in the modified intent-to-treat population, did not reach statistical significance (relative benefit: +1.33% [-0.57, 3.24], P=.17). However, a statistically significant benefit of targeted vibration was observed for participants who met the prespecified per-protocol compliance criterion (averaged ≥3 treatment sessions/week): -0.48% [-2.12, 1.17]) and -2.84% [-4.21, -1.47] (n = 73, P=.028) for Active and Sham groups, respectively. Similarly, in this compliant cohort, targeted vibration provided a statistically significant benefit on vertebral bone density, with the percentage change in vBMD of -0.29% [-1.28, 0.70] and -1.97% [-2.92, -1.01] (P=.016) for the Active and Sham groups, respectively. The vibration therapy was well-tolerated, and there were no serious device-related adverse events. These results demonstrate that targeted vibration is safe and, in adherent individuals, can significantly mitigate the decline in vertebral bone strength and vertebral bone density in postmenopausal women with osteopenia.

Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.

ABSTRACTHumans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross‐linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic‐loading fatigue life, we conducted total‐body, acute, gamma‐irradiation experiments on skeletally mature (17‐week‐old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short‐term (11‐day) or long‐term (12‐week) time point after exposure. Micro‐computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post‐exposure, 5 Gy irradiation significantly reduced trabecular mass (p < 0.001), altered microarchitecture (eg, connectivity density p < 0.001), and increased collagen cross‐links (p < 0.001). Despite these changes, vertebral strength (p = 0.745) and fatigue life (p = 0.332) remained unaltered. At 12 weeks after 5 Gy exposure, the trends in trabecular bone persisted; in addition, regardless of irradiation, cortical thickness (p < 0.01) and fatigue life (p < 0.01) decreased. These results demonstrate that the highly significant effects of 5 Gy total‐body irradiation on the trabecular bone morphology and collagen cross‐links did not translate into detectable effects on vertebral mechanics. The only mechanical deficits observed were associated with aging. Together, these vertebral results suggest that for spaceflight, irradiation alone will likely not alter failure properties, and for radiotherapy, more investigations that include post‐exposure time as a positive control and testing of both failure modalities are needed to determine the cause of increased fracture risk. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Change in vertebral strength and bone mineral density in men and women over the year post-hip fracture: a subgroup analysis.

Compare changes over the first year post-hip fracture in vertebral bone mineral density (BMD) and compressive strength, measured from quantitative computed tomography (QCT) scans of the spine (T12-L1), between women and men. QCT scans were performed on 37 participants (21 men and 16 women) at 2 and 12 months post-hip fracture as part of an ancillary observational study of hip fracture recovery in older community-dwelling men and women. Vertebral BMD and compressive strength were calculated using VirtuOst® (O.N. Diagnostics, Berkeley, CA). Unpaired t-tests were used to compare men and women with respect to baseline demographics, measurements of BMD and bone strength for the whole vertebra and the cortical and trabecular compartments, and any changes in these parameters between months 2 and 12. At 2 months post-fracture, there were no significant sex differences in any measurements of vertebral strength or BMD. Between months 2 and 12, vertebral strength decreased significantly in women (- 3.8%, p < 0.05) but not in men (- 2.3%, p < 0.20), vertebral trabecular BMD decreased similarly in both sexes (- 5.7% women; - 6.0% men), but cortical BMD did not change for either sex. Despite the small sample size, these findings suggest that appreciable loss of vertebral trabecular bone can occur for both sexes in the year following hip fracture, which may increase the risk of subsequent vertebral fracture, particularly for women.

Association Between Liver Fat and Bone Density is Confounded by General and Visceral Adiposity in a Community-Based Cohort.

Nonalcoholic fatty liver disease (NAFLD) is associated with low bone mineral density (BMD); however, it is not known whether early-stage NAFLD may be associated with BMD after accounting for BMI or visceral adipose tissue (VAT). This was a cross-sectional study of 3,462 Framingham Heart Study participants who underwent computed tomographic measurement of liver fat, VAT volume, volumetric spine BMD, vertebral cross-sectional area (CSA), and vertebral compressive strength. This study excluded heavy alcohol consumers. Multivariable linear regression models were used to assess the association between NAFLD and volumetric BMD, CSA, and vertebral compressive strength after accounting for covariates, including BMI or VAT. A total of 2,253 participants (mean age, 51.2 [SD 10.7] years; 51.1% women) were included. In multivariable-adjusted models, positive associations between NAFLD and integral BMD, trabecular BMD, and vertebral compressive strength were observed. However, results were attenuated and no longer significant after additionally adjusting for BMI or VAT. NAFLD was observed to be weakly associated with a lower vertebral CSA in adjusted models. In a community-based cohort, the associations between NAFLD and BMD and vertebral strength were confounded by BMI and VAT. However, NAFLD was associated with a reduced vertebral CSA in adjusted models.

Examination of Prediction Method of Vertebral Compressive Strength using Machine Learning

Examination of Prediction Method of Vertebral Compressive Strength using Machine Learning

Effect of variations in tissue-level ductility on human vertebral strength.

Although the ductility of bone tissue is a unique element of bone quality and varies with age and across the population, the extent to which and mechanisms by which typical population-variations in tissue-level ductility can alter whole-bone strength remains unclear. To provide insight, we conducted a finite element analysis parameter study of whole-vertebral (monotonic) compressive strength on six human L1 vertebrae. Each model was generated from micro-CT scans, capturing the trabecular micro-architecture in detail, and included a non-linear constitutive model for the bone tissue that allowed for plastic yielding, different strengths in tension and compression, large deformations, and, uniquely, localized damage once a specified limit in tissue-level ultimate strain was exceeded. Those strain limits were based on reported (mean±SD) values from cadaver experiments (8.8±3.7% strain for trabecular tissue and 2.2±0.9% for cortical tissue). In the parameter study, the strain limits were varied by ±1 SD from their mean values, for a combination of nine analyses per specimen; bounding values of zero and unlimited post-yield strain were also modeled. The main outcomes from the finite element analysis were the vertebral compressive strength and the amount of failed (yielded or damaged) tissue at the overall structure-level failure. Compared to a reference case of using the mean values of ultimate strain, we found that varying both trabecular and cortical tissue ultimate strains by ±1 SD changed the computed vertebral strength by (mean±SD)±6.9±1.1% on average. Mechanistically, that modest effect arose because the proportion of yielded tissue (without damage) was 0.9±0.3% of all the bone tissue across the nine cases and the proportion of damaged tissue (i.e. tissue exceeding the prescribed tissue-level ultimate strain) was 0.2±0.1%. If the types of variations in tissue-level ductility investigated here accurately represent real typical variations in the population, the consistency of our results across specimens and the modest effect size together suggest that typical variations in tissue-level ductility only have a modest impact on vertebral compressive strength, in large part because so few trabeculae are damaged at the load capacity of the bone.

Prediction of incident vertebral fracture using CT-based finite element analysis.

We aimed to determine the association between vertebral strength by quantitative computed tomography (CT)-based finite element analysis (FEA) and incident vertebral fracture (VF). In addition, we examined sensitivity and specificity of previously proposed diagnostic thresholds for fragile bone strength and low BMD in predicting VF. In a case-control study, 26 incident VF cases (13 men, 13 women) and 62 age- and sex-matched controls aged 50 to 85years were selected from the Framingham multi-detector computed tomography cohort. Vertebral compressive strength, integral vBMD, trabecular vBMD, CT-based BMC, and CT-based aBMD were measured from CT scans of the lumbar spine. Lower vertebral strength at baseline was associated with an increased risk of new or worsening VF after adjusting for age, BMI, and prevalent VF status (odds ratio (OR) = 5.2 per 1 SD decrease, 95% CI 1.3-19.8). Area under receiver operating characteristic (ROC) curve comparisons revealed that vertebral strength better predicted incident VF than CT-based aBMD (AUC = 0.804 vs. 0.715, p = 0.05) but was not better than integral vBMD (AUC = 0.815) or CT-based BMC (AUC = 0.794). Additionally, proposed fragile bone strength thresholds trended toward better sensitivity for identifying VF than that of aBMD-classified osteoporosis (0.46 vs. 0.23, p = 0.09). This study shows an association between vertebral strength measures and incident vertebral fracture in men and women. Though limited by a small sample size, our findings also suggest that bone strength estimates by CT-based FEA provide equivalent or better ability to predict incident vertebral fracture compared to CT-based aBMD. Our study confirms that CT-based estimates of vertebral strength from FEA are useful for identifying patients who are at high risk for vertebral fracture.

Prediction of lumbar vertebral body compressive strength of overweight and obese older adults using morphed subject-specific finite-element models to evaluate the effects of weight loss.

Diet and exercise can promote weight loss in older adults; however, there is potential to increase fracture risk due to loss of bone mineral density (BMD) known to accompany weight loss. Weight loss effects on measures of bone quality and strength are currently unknown. The purpose of this study is to develop subject-specific finite-element (FE) models of the lumbar spine and study the effect of intentional weight loss on bone strength in a pilot data set. Computed tomography (CT) scans of the lumbar spine of 30 overweight and obese (mean BMI = 29.7 ± 3.9kg/m2), older adults (mean age = 65.9 ± 4.6years) undergoing an 18-month intentional weight loss intervention were obtained at baseline and post-intervention. Measures of volumetric BMD (vBMD) and variable cortical thickness were derived from each subject CT scan. Development of the subject-specific FE models of the lumbar spine involved model morphing techniques to accelerate the development of the models. vBMD-derived material properties and cortical thickness measures were directly mapped to baseline and post-intervention models. Bone strength was estimated through simulation of a quasi-static uniaxial compression test. From baseline to 18-month post-weight loss intervention, there were statistically significant decreases in estimated bone strength (6.5% decrease; p < 0.05). Adjusting for baseline bone measures and gender revealed no statistically significant correlations between weight change and change in vBMD, cortical thickness, or bone strength. Integration of CT-based measures and FE models with conventional areal BMD can improve the understanding of the effects of intentional weight loss on bone health.

Higher Dairy Food Intake Is Associated With Higher Spine Quantitative Computed Tomography (QCT) Bone Measures in the Framingham Study for Men But Not Women.

Previous studies found that dairy foods were associated with higher areal bone mineral density (BMD). However, data on bone geometry or compartment-specific bone density is lacking. In this cross-sectional study, the association of milk, yogurt, cheese, cream, milk+yogurt, and milk+yogurt+cheese intakes with quantitative computed tomography (QCT) measures of bone were examined, and we determined if associations were modified by serum vitamin D (25-OH D, tertiles) or age (<50 versus ≥50 years). Participants were 1522 men and 1104 women (aged 32 to 81 years, mean 50 years [men]; 55 years [women]) from the Framingham Heart Study with measures of dairy food intake (servings/wk) from a food-frequency questionnaire, volumetric BMD (vBMD, integral and trabecular, g/cm3 ), cross-sectional area (CSA, cm2 ), and estimated vertebral compressive strength (VCS, N) and 25-OH D (radioimmunoassay). Sex-specific multivariable linear regression was used to calculate the association of dairy food intake (energy adjusted) with each QCT measure, adjusting for covariates. Mean milk intake ±SD was 6 ± 7 servings/week in both men and women. In men, higher intake of milk, milk+yogurt, and milk+yogurt+cheese was associated with higher integral (p = 0.001 to 0.006) and trabecular vBMD (p = 0.006 to 0.057) and VCS (p = 0.001 to 0.010). Further, a higher cheese intake was related with higher CSA (p = 0.049). In women, no significant results were observed for the dairy foods, except for a positive association of cream intake with CSA (p = 0.016). The associations appeared to be stronger in older men. Across 25-OH D tertiles, dairy was positively associated with bone health. In summary, men with higher intakes of milk, milk+yogurt, and milk+yogurt+cheese had higher trabecular and integral vBMD and VCS but not CSA. Dairy intake seems to be most beneficial for older men, and dairy continued to have positive associations among all 25-OH D levels. © 2018 American Society for Bone and Mineral Research.

Effects of a bone graft substitute consisting of porous gradient HA/ZrO2 and gelatin/chitosan slow-release hydrogel containing BMP-2 and BMSCs on lumbar vertebral defect repair in rhesus monkey.

Dense biomaterial plays an important role in bone replacement. However, it fails to induce bone cell migration into graft material. In the present study, a novel bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. The morphological characteristics of the BGS evaluated by a scanning electron microscope showed that it had a three-dimensional network structure with uniformly distributed chitosan microspheres on the surfaces of the graft material and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testing for bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed to examine the reparative efficacy of the BGS and PGHC. The BGS displayed excellent ability to repair the lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scanning, and histomorphological characterization showed that the newly formed bone volume in the interior of the pores in the BGS was significantly higher than in the PGHC. The results of biomechanical testing indicated that the vertebral body compression strength of the PGHC implant was lower than the other implants. Reverse-transcription polymerase chain reaction and western blot analyses showed that the expression of bone-related proteins in the BGS implant was significantly higher than in the PGHC implant. The BGS displayed reparative effects similar to autologous bone. Therefore, BGS use in vertebral bone defect repair appears promising.

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta

In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios.

Novel porous gradient HA/ZrO2 engineering bone carrying gelatin/chitosan slow-release hydrogel loading BMP-2 and BMSCs repair vertebra defect in rhesus macaque

Objective To examine the bone regeneration capability of a novel bone graft substitute (BGS) of porous gradient HA/ZrO2 carrying BMP-2 and BMSCs in gelatin/chitosan slow-release hydrogel (BBGC-h) to lumbar vertebral body defect in rhesus monkey. Methods The BBGC-h was evaluated by scanning electron microscope for its morphological characteristics. The BGS with or without BBGC-h was implanted into the lumbar vertebral body defects in rhesus monkeys. Twenty-four healthy rhesus monkeys (5-7 years, 5-8 kg) were provided by the Kunming Institute of Zoology, Chinese Academy of Sciences. They were randomly divided into groups A (Test, BGC_BBCG-h, n=10), B (Control, BGC, n=10) and C (Autologous, n=4), respectively. The anteroposterior and lateral radiographs of the lumbar spine were conducted under anesthesia at 24 h, 8 weeks, and 16 weeks postoperatively. Micro-CT and histomorphometry were performed on samples collected from 2 of 10 samples in each group A and B to observe the newly formed bone volume at 8 and 16 weeks postoperatively. At 16 weeks postoperatively, bone matrix composition markers, including typeⅠcollagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase and vascular endothelial growth factor, were analyzed for groups A and B by RT-PCR and Western Blot. Biomechanical testing was performed on harvested vertebral samples of 4 animals from each of the subgroups and 4 additional non-operated healthy animals. Results The BGS revealed a three-dimensional network structure with uniformly distributed chitosan micro-spheres on the surfaces of the material and the interior of the pores. Hydrogel encapsulated BMSCs were visible in the pores of the BGS. The newly formed bone volume in the interior of the pores in the group A was significantly higher than that in the group B at the two time points after surgery via Micro-CT scanning and histomorphology. The results of biomechanical testing indicated that the vertebral body compression strength was the smallest in the group B compared with those of the other groups and the non-operated healthy group (P <0.05), while the energy to maximal load of group A and group C were higher than those of group B. There were significant higher protein expression of typeⅠcollagen, OCN, OPN, bFGF, ALP and VEGF in group A than in group B (P <0.05). Conclusion There may be a promising to use BGS_BBGC-h to repair vertebral bone defects. The novel bone graft substitute has similar effects compared with autologous bone. Key words: Gelatin; Chitosan; Hydrogel; Bone morphogenetic protein 2; Mesenchymal stem cells; Ceramics; Tissue engineering

Vertebral Body Compressive Strength Evaluated by Dual-Energy X-Ray Absorptiometry and Hounsfield Units In Vitro

Dual-energy X-ray absorptiometry (DXA) and Hounsfield unit (HU) are 2 technologies used in vivo to assess bone mineral density and to predict fracture risk. However, few in vitro studies focus on the difference between the 2 technologies in the ability to determine vertebral body compressive strength. Forty-two lumbar vertebrates were harvested from 7 mature goats. All the vertebrae were imaged using clinical computed tomography and assessed by DXA subsequently. The individual vertebral body was then mechanically tested to failure in compression, to determine ultimate load and stress. HU has a moderate correlation with DXA (r = 0.64). DXA has significant associations with ultimate load and stress (r = 0.59 and 0.69, respectively). Significant positive linear correlations were also found between HU and ultimate load (r = 0.65) and stress (r = 0.81). There was no significant difference between HU and DXA to predict the ultimate load (t = 0.56, p = 0.577) or the ultimate stress (t = 1.62, p = 0.112). HU has an equal predictive value as the DXA for whole vertebral body compressive strength. This work supports the application of the HU measurement using clinical computed tomography imaging technology to assess bone strength and fracture risk.

Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis.

Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm³) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm³ or lower) and fragile bone strength (vertebral strength of 4500 N or lower). Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. 3.

Reinforcing effect of calcium sulfate cement bovine bone morphogenetic protein on vertebral in the rabbit model of osteoporosis

ObjectiveTo observe reinforcing effect of calcium sulfate cement (CSC) bovine bone morphogenetic protein (bBMP) on vertebral in the rabbit model of osteoporosis. MethodsA total of 48 New Zealand white rabbits were randomly divided into group I (blank control group), group II (CSC injection group), group III (CSC/bBMP injection group) and control group. White rabbit osteoporosis model was established rapidly by using castration method+methylprednisolone candidate. After modeling, groups II, III were given corresponding vertebral body injection material, and 4 animals were sacrificed respectively at 24 h, 6 weeks, 12 weeks after vertebral plasty. Tissue pathological status, vertebral mineral density and vertebral body bone mechanical strength were observed. ResultsVertebral body structure form was normal in the groups II and III. Trabecular bone coarsens, connection and repair were observed in micro fracture and bone defects, bone trabecular connectivity was superior to group I significantly; vertebral body compression strength in the groupI was on the decline, vertebral compression strength in the groups IIand III was on the rise, the largest vertebra. Postoperative BMC and BMD in groups IIand III were incresed, and significantly higher than group I after 6 weeks (P<0.05), BMC and BMD in group III after 12 weeks were higher than the other three groups. ConclusionCompound bBMP CSC has good bone induction. It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula, and can significantly improve the vertebral strength, as a vertebral packing material with good application prospect.

Locally measured microstructural parameters are better associated with vertebral strength than whole bone density

Whole vertebrae areal and volumetric bone mineral density (BMD) measurements are not ideal predictors of vertebral fractures. We introduce a technique which enables quantification of bone microstructural parameters at precisely defined anatomical locations. Results show that local assessment of bone volume fraction at the optimal location can substantially improve the prediction of vertebral strength. Whole vertebrae areal and volumetric BMD measurements are not ideal predictors of vertebral osteoporotic fractures. Recent studies have shown that sampling bone microstructural parameters in smaller regions may permit better predictions. In such studies, however, the sampling location is described only in general anatomical terms. Here, we introduce a technique that enables the quantification of bone volume fraction and microstructural parameters at precisely defined anatomical locations. Specific goals of this study were to investigate at what anatomical location within the vertebrae local bone volume fraction best predicts vertebral-body strength, whether this prediction can be improved by adding microstructural parameters and to explore if this approach could better predict vertebral-body strength than whole bone volume fraction and finite element (FE) analyses. Eighteen T12 vertebrae were scanned in a micro-computed tomography (CT) system and FE meshes were made using a mesh-morphing tool. For each element, bone microstructural parameters were measured and correlated with vertebral compressive strength as measured experimentally. Whole bone volume fraction and FE-predicted vertebral strength were also compared to the experimental measurements. A significant association between local bone volume fraction measured at a specific central region and vertebral-body strength was found that could explain up to 90% of the variation. When including all microstructural parameters in the regression, the predictive value of local measurements could be increased to 98%. Whole bone volume fraction could explain only 64% and FE analyses 76% of the variation in bone strength. A local assessment of volume fraction at the optimal location can substantially improve the prediction of bone strength. Local assessment of other microstructural parameters may further improve this prediction but is not clinically feasible using current technology.

Vertebral size, bone density, and strength in men and women matched for age and areal spine BMD.

To explore the possible mechanisms underlying sex-specific differences in skeletal fragility that may be obscured by two-dimensional areal bone mineral density (aBMD) measures, we compared quantitative computed tomography (QCT)-based vertebral bone measures among pairs of men and women from the Framingham Heart Study Multidetector Computed Tomography Study who were matched for age and spine aBMD. Measurements included vertebral body cross-sectional area (CSA, cm(2) ), trabecular volumetric BMD (Tb.vBMD, g/cm(3) ), integral volumetric BMD (Int.vBMD, g/cm(3) ), estimated vertebral compressive loading and strength (Newtons) at L3 , the factor-of-risk (load-to-strength ratio), and vertebral fracture prevalence. We identified 981 male-female pairs (1:1 matching) matched on age (± 1 year) and QCT-derived aBMD of L3 (± 1%), with an average age of 51 years (range 34 to 81 years). Matched for aBMD and age, men had 20% larger vertebral CSA, lower Int.vBMD (-8%) and Tb.vBMD (-9%), 10% greater vertebral compressive strength, 24% greater vertebral compressive loading, and 12% greater factor-of-risk than women (p < 0.0001 for all), as well as higher prevalence of vertebral fracture. After adjusting for height and weight, the differences in CSA and volumetric bone mineral density (vBMD) between men and women were attenuated but remained significant, whereas compressive strength was no longer different. In conclusion, vertebral size, morphology, and density differ significantly between men and women matched for age and spine aBMD, suggesting that men and women attain the same aBMD by different mechanisms. These results provide novel information regarding sex-specific differences in mechanisms that underlie vertebral fragility.

Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur

With the increasing prevalence of obesity among children and adolescents, it is imperative to understand the implications of early diet-induced obesity on bone health. We hypothesized that cancellous bone of skeletally immature mice is more susceptible to the detrimental effects of a high fat diet (HFD) than mature mice, and that removing excess dietary fat will reverse these adverse effects. Skeletally immature (5weeks old) and mature (20weeks old) male C57BL/6J mice were fed either a HFD (60% kcal fat) or low fat diet (LFD; 10% kcal fat) for 12weeks, at which point, the trabecular bone structure in the distal femoral metaphysis and third lumbar vertebrae were evaluated by micro-computed tomography. The compressive strength of the vertebrae was also measured. In general, the HFD led to deteriorations in cancellous bone structure and compressive biomechanical properties in both age groups. The HFD-fed immature mice had a greater decrease in trabecular bone volume fraction (BVF) in the femoral metaphysis, compared to mature mice (p=0.017 by 2-way ANOVA). In the vertebrae, however, the HFD led to similar reductions in BVF and compressive strength in the two age groups. When mice on the HFD were switched to a LFD (HFD:LFD) for an additional 12weeks, the femoral metaphyseal BVF in immature mice showed no improvements, whereas the mature mice recovered their femoral metaphyseal BVF to that of age-matched lean controls. The vertebral BVF and compressive strength of HFD:LFD mouse bones, following diet correction, were equivalent to those of LFD:LFD mice in both age groups. These data suggest that femoral cancellous metaphyseal bone is more susceptible to the detrimental effects of HFD before skeletal maturity and is less able to recover after correcting the diet. Negative effects of HFD on vertebrae are less severe and can renormalize with LFD:LFD mice after diet correction, in both skeletally immature and mature animals.

Clinical versus pre-clinical FE models for vertebral body strength predictions

The finite element analysis is an accepted method to predict vertebral body compressive strength. This study compares measurements obtained from in vitro tests with the ones from two different simulation models: clinical quantitative computer tomography (QCT) based homogenized finite element (hFE) models and pre-clinical high-resolution peripheral QCT-based (HR-pQCT) hFE models.About 37 vertebral body sections were prepared by removing end-plates and posterior elements, scanned with QCT (390/450μm voxel size) as well as HR-pQCT (82μm voxel size), and tested in compression up to failure. Non-linear viscous damage hFE models were created from QCT/HT-pQCT images and compared to experimental results based on stiffness and ultimate load.As expected, the predictability of QCT/HR-pQCT-based hFE models for both apparent stiffness (r2=0.685/0.801) and strength (r2=0.774/0.924) increased if a better image resolution was used. An analysis of the damage distribution showed similar damage locations for all cases.In conclusion, HR-pQCT-based hFE models increased the predictability considerably and do not need any tuning of input parameters. In contrast, QCT-based hFE models usually need some tuning but are clinically the only possible choice at the moment.

Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation

Effects of cladrin treatment and withdrawal in osteopenic rats were studied. Cladrin improved trabecular microarchitecture, increased lumbar vertebral compressive strength, augmented coupled remodeling, and increased bone osteogenic genes. A significant skeletal gain was maintained 4weeks after cladrin withdrawal. Findings suggest that cladrin has significant positive skeletal effects. We showed that a standardized extract of Butea monosperma preserved trabecular bone mass in ovariectomized (OVx) rats. Cladrin, the most abundant bioactive compound of the extract, promoted peak bone mass achievement in growing rats by stimulating osteoblast function. Here, we studied the effects of cladrin treatment and withdrawal on the osteopenic bones. Adult female Sprague-Dawley rats were OVx and left untreated for 12weeks to allow for significant estrogen deficiency-induced bone loss, at which point cladrin (1 and 10mg/kg/day) was administered orally for another 12weeks. Half of the rats were killed at the end of the treatments and the other half at 4weeks after treatment withdrawal. Sham-operated rats and OVx rats treated with PTH or 17β-estradiol (E2) served as various controls. Efficacy was evaluated by bone microarchitecture using microcomputed tomographic analysis and fluorescent labeling of bone. qPCR and western blotting measured mRNA and protein levels in bone and uterus. Specific ELISA was used for measuring levels of serum PINP and urinary CTx. In osteopenic rats, cladrin treatment dose dependently improved trabecular microarchitecture, increased lumbar vertebral compression strength, bone formation rate (BFR), cortical thickness (Cs.Th), serum PINP levels, and expression of osteogenic genes in bones; and reduced expression of bone osteoclastogenic genes and urinary CTx levels. Cladrin had no uterine estrogenicity. Cladrin at 10mg/kg maintained acquired skeletal gains 4weeks after withdrawal. Cladrin had positive skeletal effects in osteopenic rats that were maintained after treatment withdrawal.