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Children with type 1 diabetes (T1D) experience an increased risk of fracture, which may be related to altered bone development. We aimed to assess differences in bone, muscle and physical activity (PA), and explore if better muscle and PA measures would mitigate bone differences between children and adolescents with T1D and typically developing peers (TDP). We matched 56 children and adolescents with T1D (mean age 11.9 yrs) and 56 TDP (11.5 yrs) by sex and maturity from 171 participants with T1D and 66 TDP (6-17 yrs). We assessed the distal radius and tibia with high-resolution peripheral quantitative computed tomography (HR-pQCT), and the radius and tibia shaft bone and muscle with pQCT. We also measured muscle function from force-related measures in neuromuscular performance tests (push-up, grip test, countermovement and long jump). We compared PA based on questionnaire scores and accelerometers between groups. Bone, muscle, and neuromuscular performance measures were compared using MANOVA. We used mediation to explore the role of PA and muscle in bone differences. Children and adolescents with T1D had 6-10 % lower trabecular density, bone volume fraction, thickness and number at both distal radius and tibia, and 11 % higher trabecular separation at the distal radius than TDP. They also had 3-16 % higher cortical and tissue mineral density, and cortical thickness at the distal radius, 5-7 % higher cortical density and 1-3 % higher muscle density at both shaft sites compared to TDP. PA mediated the between-group difference in trabecular number (indirect effect -0.04) at the distal radius. Children and adolescents with T1D had lower trabecular bone density and deficits in trabecular micro-architecture, but higher cortical bone density and thickness at the radius and tibia compared to TDP. They engaged in less PA but had comparable muscle measures to those of TDP. PA participation may assist in mitigating deficit in trabecular number observed in children and adolescents with T1D., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: En-bloc resection of giant cell tumors (GCTs) of the distal radius remains the mainstay treatment for those with high-graded lesions. Several techniques have been described for reconstruction of the resected segment, of which transposition of the ipsilateral ulna is scarcely reported., Objectives: To investigate the efficacy and safety of the different techniques of ulnar translocation following GCTs total resection., Methods: A systematic review and meta-analysis was conducted concerning the reported functional outcomes, including grip strength, range of forearm motion, functional scores, and new bone formation, as well as postoperative complications, such as delayed union, local recurrence and metastasis. The ranges of functional outcomes were reviewed and the pooled prevalence rates of complication and their respective 95% confidence intervals (95% CIs) were computed., Results: In a total of 12 studies, 90 patients (51.1% males, 84.8% had Campanacci grade III tumors) underwent five different reconstruction techniques. As compared to the normal side, the mean grip strength in the affected side ranged between 59 and 71%. The average union time was 1-8 months, while delayed union was reported in 50% (95% CI, 15.35 to 84.65) of patients whom their grafts were fixed with Steinmann pins. The shortest union time, the highest forearm supination and pronation degrees, new bone formation at the ulnar stump, and the highest functional scores were reported following a modified distal radius plate technique. Using a dynamic compression plate and a clover leaf plate provided lower, but considerable, functional outcomes., Conclusion: Ulnar translocation following GCT en-bloc resection warrants additional investigation in large cohorts and well-designed studies to corroborate the promising outcomes presented in this review., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification, is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on initiation stage of bone healing and underlying mechanism were thoroughly investigated in vitro and in vivo. Intriguingly, apart from its superiority in stem cell recruitment to BMP-2, IL-8 not only endowed a histological "prep-state" of endochondral ossification by up-regulating chondrogenic genes and inducing the formation of extensive cartilage tissues, facilitating rapid bone transformation by BMP-2, but also triggered a cellular "prep-state" with high expression of BMP receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid initiation including efficient stem cell recruitment and a "chondrogenic/osteogenic balance" at the first stage of endochondral ossification, and the scaffold facilitated sufficient osteoconductivity, together resulting in early extensive bone mineralization and an advanced regeneration throughout the repair of large bone defect. We believe this new idea could provide insights toward designing bone-repairing biomaterials with higher regenerative efficiency., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Forward falls represent a risk of injury for the elderly. The risk is increased in elderly persons with bone diseases, such as osteoporosis. However, half of the patients with fracture were not considered at risk based on bone density measurement (current clinical technique). We assume that loading conditions are of high importance and should be considered. Real loading conditions in a fall can reach a loading speed of 2m/s on average. The current study aimed to apply more realistic loading conditions that simulate a forward fall on the radius ex vivo. Thirty radii from elderly donors (79y.o.±12y.o., 15 males, 15 females) were loaded at 2m/s using a servo-hydraulic testing machine to mimic impact that corresponds to a fall. Among the 30 radii, 14 had a fracture after the impact, leading to two groups (fractured and non-fractured). Surfacic strain fields were measured using stereovision and allow for visualization of fracture patterns. The average maximum load was 2963±1274N. These experimental data will be useful for assessing the predictive capability of fracture risk prediction methods such as finite element models., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Boys with autism spectrum disorder (ASD) have lower areal bone mineral density (aBMD) than typically developing controls (TDC). Studies of volumetric BMD (vBMD) and bone microarchitecture provide information about fracture risk beyond that provided by aBMD but are currently lacking in ASD., Objectives: To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC., Design/methods: Cross-sectional study of 34 boys (16 ASD, 18 TDC) that assessed (i) aBMD at the whole body (WB), WB less head (WBLH), hip and spine using dual X-ray absorptiometry (DXA), (ii) vBMD and bone microarchitecture at the ultradistal radius and distal tibia using high-resolution peripheral quantitative CT (HRpQCT), and (iii) bone strength estimates (stiffness and failure load) using micro-finite element analysis (FEA). We controlled for age in all groupwise comparisons of HRpQCT and FEA measures. Activity questionnaires, food records, physical exam, and fasting levels of 25(OH) vitamin D and bone markers (C-terminal collagen crosslinks and N-terminal telopeptide (CTX and NTX) for bone resorption, N-terminal propeptide of Type 1 procollagen (P1NP) for bone formation) were obtained., Results: ASD participants were slightly younger than TDC participants (13.6 vs. 14.2years, p=0.44). Tanner stage, height Z-scores and fasting serum bone marker levels did not differ between groups. ASD participants had higher BMI Z-scores, percent body fat, IGF-1 Z-scores, and lower lean mass and aBMD Z-scores than TDC at the WB, WBLH, and femoral neck (P<0.1). At the radius, ASD participants had lower trabecular thickness (0.063 vs. 0.070mm, p=0.004), compressive stiffness (56.7 vs. 69.7kN/mm, p=0.030) and failure load (3.0 vs. 3.7kN, p=0.031) than TDC. ASD participants also had 61% smaller cortical area (6.6 vs. 16.4mm 2 , p=0.051) and thickness (0.08 vs. 0.22mm, p=0.054) compared to TDC. At the tibia, ASD participants had lower compressive stiffness (183 vs. 210kN/mm, p=0.048) and failure load (9.4 vs. 10.8kN, p=0.043) and 23% smaller cortical area (60.3 vs. 81.5mm 2 , p=0.078) compared to TDC. A lower proportion of ASD participants were categorized as "very physically active" (20% vs. 72%, p=0.005). Differences in physical activity, calcium intake and IGF-1 responsiveness may contribute to group differences in stiffness and failure load., Conclusion: Bone microarchitectural parameters are impaired in ASD, with reductions in bone strength estimates (stiffness and failure load) at the ultradistal radius and distal tibia. This may result from lower physical activity and calcium intake, and decreased IGF-1 responsiveness., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Fractures of the distal section of the radius (Colles' fractures) occur earlier in life than other osteoporotic fractures. Therefore, they can be interpreted as a warning signal for later, more deleterious fractures of vertebral bodies or the femoral neck. In the past decade, the advent of HR-pQCT allowed a detailed architectural analysis of the distal radius and an automated but time-consuming estimation of its strength with linear micro-finite element (μFE) analysis. Recently, a second generation of HR-pQCT scanner (XtremeCT II, SCANCO Medical, Switzerland) with a resolution beyond 61 μm became available for even more refined biomechanical investigations in vivo. This raises the question how biomechanical outcome variables compare between the original (LR) and the new (HR) scanner resolution. Accordingly, the aim of this work was to validate experimentally a patient-specific homogenized finite element (hFE) analysis of the distal section of the human radius for the fast prediction of Colles' fracture load based on the last generation HR-pQCT. Fourteen pairs of fresh frozen forearms (mean age = 77.5±9) were scanned intact using the high (61 μm) and the low (82 μm) resolution protocols that correspond to the new and original HR-pQCT systems. From each forearm, the 20mm most distal section of the radius were dissected out, scanned with μCT at 16.4 μm and tested experimentally under compression up to failure for assessment of stiffness and ultimate load. Linear and nonlinear hFE models together with linear micro finite element (μFE) models were then generated based on the μCT and HR-pQCT reconstructions to predict the aforementioned mechanical properties of 24 sections. Precision errors of the short term reproducibility of the FE analyses were measured based on the repeated scans of 12 sections. The calculated failure loads correlated strongly with those measured in the experiments: accounting for donor as a random factor, the nonlinear hFE provided a marginal coefficient of determination (R m 2 ) of 0.957 for the high resolution (HR) and 0.948 for the low resolution (LR) protocols, the linear hFE with R m 2 of 0.957 for the HR and 0.947 for the LR protocols. Linear μFE predictions of the ultimate load were similar with an R m 2 of 0.950 for the HR and 0.954 for the LR protocols, respectively. Nonlinear hFE strength computation led to precision errors of 2.2 and 2.3% which were higher than the ones calculated based on the linear hFE (1.6 and 1.9%) and linear μFE (1.2 and 1.6%) for the HR and LR protocols respectively. Computation of the fracture load with nonlinear hFE demanded in average 6h of CPU time which was 3 times faster than with linear μFE, while computation with linear hFE took only a few minutes. This study delivers an extensive experimental and numerical validation for the application of an accurate and fast hFE diagnostic tool to help in identifying individuals who may be at risk of an osteoporotic wrist fracture and to follow up pharmacological and other treatments in such patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue., (Published by Elsevier Inc.)

Purpose: Chronic heavy alcohol consumption is associated with bone density loss and increased fracture risk, while low levels of alcohol consumption have been reported as beneficial in some studies. However, studies relating alcohol consumption to bone geometry, volumetric bone mineral density (vBMD) and bone microarchitecture, as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), are lacking., Methods: Here we report an analysis from the Hertfordshire Cohort Study, in which we studied associations between HR-pQCT measures at the distal radius and tibia and alcohol consumption in 376 participants (198 men and 178 women) aged 72.1-81.4 years., Results: A total of 30 (15.2%), 90 (45.5%) and 78 (39.4%) men drank minimal/none (<1 unit/week), low (≥1 unit/week and <11 units/week) and moderate/high (≥11 units/week) amounts of alcohol respectively. These figures were 74 (41.8%), 80 (45.2%) and 23 (13.0%) respectively in women for minimal/none (<1 unit/week), low (≥1 unit/week and <8 units/week) and moderate/high (≥8 units/week). At the distal radius, after adjustment for confounding factors (age, BMI, smoking status, dietary calcium intake, physical activity and socioeconomic status and years since menopause and HRT use for women), men that drank low alcohol had lower cortical thickness (p=0.038), cortical vBMD (p=0.033), and trabecular vBMD (p=0.028) and higher trabecular separation (p=0.043) than those that drank none/minimal alcohol. Similar differences were shown between minimal/none and moderate/high alcohol although these only reached statistical significance for the cortical parameters. Interestingly, after similar adjustment, women showed similar differences in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia. However, women that drank moderate/high alcohol had significantly higher trabecular vBMD (p=0.007), trabecular thickness (p=0.026), and trabecular number (p=0.042) and higher trabecular separation (p=0.026) at the distal radius than those that drank low alcohol., Conclusions: Our results suggest that alcohol consumption (low and moderate/high) may have a detrimental impact on bone health in men in both the cortical and trabecular compartments at the distal radius with similar results in women in the trabecular compartment between none/minimal alcohol and low alcohol at the distal tibia suggesting that avoidance of alcohol may be beneficial for bone health., (Copyright © 2015. Published by Elsevier Inc.)

Bone tuberculosis (TB) is one of the most common extrapulmonary TB. Effective integration of chemotherapy and bone regeneration is an optimal solution for bone TB therapy. Herein, we produce a composite scaffold drug delivery system fabricated with an isoniazid conjugated star poly(lactide-co-glycolide) (PLGA-INH4) and β-TCP. The cytological assay indicated the composite system possesses good biocompatibility. The in vitro and in vivo drug release evaluations showed that the composite system can intactly release the pristine INH and maintain effective INH concentration in a controlled manner for more than 100 days, and achieve high localized drug concentration and low systemic drug concentration. The rabbit radius repair experiment testified the scaffold has good bone regeneration capacity. Our work demonstrate the composite system can simultaneously achieve localized long-term drug controlled release and bone regeneration, which provides a promising route for improved bone TB treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Non healing bone defects remain a worldwide health problem and still only few osteoinductive growth factors are available for clinical use in bone regeneration. By introducing BMP-2 residues into growth and differentiation factor (GDF)-5 we recently produced a mutant GDF-5 protein BB-1 which enhanced heterotopic bone formation in mice. Designed to combine positive features of GDF-5 and BMP-2, we suspected that this new growth factor variant may improve long bone healing compared to the parent molecules and intended to unravel functional mechanisms behind its action. BB-1 acquired an increased binding affinity to the BMP-IA receptor, mediated enhanced osteogenic induction of human mesenchymal stem cells versus GDF-5 and higher VEGF secretion than BMP-2 in vitro. Rabbit radius defects treated with a BB-1-coated collagen carrier healed earlier and with increased bone volume compared to BMP-2 and GDF-5 according to in vivo micro-CT follow-up. While BMP-2 callus often remained spongy, BB-1 supported earlier corticalis and marrow cavity formation, showing no pseudojoint persistence like with GDF-5. Thus, by combining positive angiogenic and osteogenic features of GDF-5 and BMP-2, only BB-1 restored a natural bone architecture within 12 weeks, rendering this promising growth factor variant especially promising for long bone regeneration., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In primary hyperparathyroidism (PHPT), protracted elevation of serum parathyroid hormone (PTH) is held to be associated with cortical, but not trabecular, bone loss. However, an alternative explanation for the apparent preservation of trabecular bone is fragmentation of the cortex by intracortical remodeling. The cortical fragments resemble trabeculae and so may be erroneously included in the quantification of 'trabecular' bone density. To test this hypothesis, we compared bone microarchitecture in 43 patients with untreated PHPT (mean 62.9 years, range 31-84) with 47 healthy age-matched controls and 25 patients with surgically treated PHPT (63.6 years, 30-82). Images of the distal radius and tibia were acquired using high-resolution peripheral quantitative CT and analysed using StrAx1.0, a new software program that quantifies bone morphology in-vivo. Results were expressed as the mean number of standardized deviations (SD) from the age-specific mean (Z scores, mean±SEM). In subjects with PHPT, total tibial cortical area was reduced -0.26±0.08 SD; p=0.002). Cortical volumetric bone mineral density (vBMD) was reduced (-0.29±0.06 SD; p<0.001) due to higher cortical porosity (0.32±0.06 SD; p<0.001) and lower tissue mineralization density (-0.21±0.06 SD; p=0.002). Medullary area was increased (0.26±0.08 SD; p=0.002) and trabecular vBMD was reduced (-0.14±0.04 SD; p<0.001). In subjects who underwent successful parathyroidectomy, cortical area (-0.18±0.10 SD; NS) and medullary area (0.18±0.10 SD; NS) did not differ from controls. Cortical vBMD was reduced (-0.15±0.05 SD; p=0.003) due to high porosity (0.15±0.05 SD; p=0.006), values numerically lower than in untreated PHPT. Tissue mineralization density (-0.26±0.04 SD; p<0.001) and trabecular vBMD were reduced (-0.16±0.04 SD, p<0.001). The results were similar in the distal radius. In PHPT, chronically elevated endogenous PTH does not spare trabecular bone; it causes bone loss and microarchitectural deterioration in both cortical and trabecular compartments of bone., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The purpose of this study was to develop a multivariate distal radius injury risk prediction model that incorporates dynamic loading variables in multiple directions, and interpret the distal radius failure data in order to establish injury probability thresholds. Repeated impacts with increasing intensity were applied to the distal third of eight human cadaveric radius specimens (mean (SD) age=61.9 (9.7)) until injury occurred. Crack (non-propagating damage) and fracture (specimen separated into at least two fragments) injury events were recorded. Best subsets analysis was performed to find the best multivariate injury risk model. Force-only risk models were also determined for comparison. Cumulative distribution functions were developed from the parameters of a Weibull analysis and the forces and risk scores (i.e., values calculated from the injury risk models) from 10% to 90% probability were calculated. According to the adjusted R(2), variance inflation factor and p-values, the model that best predicted the crack event included medial/lateral impulse, Fz load rate, impact velocity and the natural logarithm of Fz (Adj. R(2)=0.698), while the best predictive model of the fracture event included medial/lateral impulse, impact velocity and peak Fz (Adj. R(2)=0.845). The multivariate models predicted injury risk better than both the Fz-only crack (Adj. R(2)=0.551) and fracture (Adj. R(2)=0.293) models. Risk scores of 0.5 and 0.6 corresponded to 10% failure probability for the crack and fracture events, respectively. The inclusion of medial/lateral impulse and impact velocity in both crack and fracture models, and Fz load rate in the crack model, underscores the dynamic nature of these events. This study presents a method capable of developing a set of distal radius fracture prediction models that can be used in the assessment and development of distal radius injury prevention interventions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in-vivo technique used to analyze the distal radius and tibia. It provides a voxel size of 82μm. In addition to providing the usual microarchitecture parameters, local topological analysis (LTA) depicting rod- and plate-like trabeculae may improve prediction of bone fragility. Thirty-three women with prevalent wrist fractures from the OFELY cohort were compared with age-matched controls. Bone microarchitecture, including the structural model index (SMI), was assessed by HR-pQCT, and micro-finite element analysis (μFE) was computed on trabecular bone images of the distal radius (XtremeCT, Scanco Medical AG). A new LTA method was applied to label each bone voxel as a rod, plate or node. Then the bone volume fraction (BV/TV*), the rod, plate and node ratios over bone volume (RV/BV*, PV/BV*, NV/BV*) or total volume (RV/TV*, PV/TV*, NV/TV*) and the rod to plate ratio (RV/PV*) were calculated. Associations between LTA parameters and wrist fractures were computed in a conditional logistic regression model. Multivariate models were tested to predict the μFE-derived trabecular bone stiffness. RV/TV* (OR=4.41 [1.05-18.62]) and BV/TV* (OR=6.45 [1.06-39.3]), were significantly associated with prevalent wrist fracture, after adjustment for ultra distal radius aBMD. Multivariate linear models including PV/TV* or BV/TV*+RV/PV* predicted trabecular stiffness with the same magnitude as those including SMI. Conversion from plates into rods was significantly associated with bone fragility, with a negative correlation between RV/PV* and trabecular bone stiffness (r=-0.63, p<0.0001). We conclude that our local topological analysis is feasible for a voxel size of 82μm. After further validation, it may improve bone fragility description., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Colles' fracture, a transverse fracture of the distal radius bone, is one of the most frequently observed osteoporotic fractures resulting from low energy or traumatic events, associated with low and high strain rates, respectively. Although experimental studies on Colles' fracture were carried out at various loading rates ranging from static to impact loadings, there is no systematic study in the literature that isolates the influence of strain rate on Colles' fracture load. In order to provide a better understanding of fracture risk, the current study combines experimental material property measurements under varying strain rates with computational modeling and presents new information on the effect of strain rate on Colles' fracture. The simulation results showed that Colles' fracture load decreased with increasing strain rate with a steeper change in lower strain rates. Specifically, strain rate values (0.29s(-1)) associated with controlled falling without fracture corresponded to a 3.7% reduction in the fracture load. On the other hand, the reduction in the fracture load was 34% for strain rate of 3.7s(-1) reported in fracture inducing impact cadaver experiments. Further increase in the strain rate up to 18s(-1) led to an additional 22% reduction. The most drastic reduction in fracture load occurs at strain rates corresponding to the transition from controlled to impact falling. These results are particularly important for the improvement of fracture risk assessment in the elderly because they identify a critical range of loading rates (10-50mm/s) that can dramatically increase the risk of Colles' fracture., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Reduced bone mineral density (BMD) and bone mass have been observed in children with idiopathic hypercalciuria. Whether urinary calcium excretion at the higher end of the normal physiologic range can influence bone health in healthy children independent of dietary intake is unknown. Urinary calcium was quantified in 603 24-h urine samples from 154 healthy children and adolescents who had ≥3 urine collections and parallel 3-day weighed dietary records during the 4years preceding proximal forearm bone analyses by peripheral quantitative computed tomography (pQCT). Urinary potential renal acid load (uPRAL) was determined according to urine ionogram by subtracting measured quantitatively important mineral cations from nonbicarbonate anions. Urinary calcium excretion was significantly associated with volumetric (v)BMD (P=0.04), almost significantly with cortical bone mineral content (BMC) (P=0.05), but not with cortical cross-sectional area (CSA) (P=0.09), total CSA (P=0.3), or Strength-Strain Index (P=0.8) in the total population sample. Stratified analyses based on the median split of uPRAL showed that calcium excretion was negatively associated with vBMD (P=0.007), cortical BMC (P=0.001), and cortical CSA (P=0.004) in those children with higher uPRALs, but not in those with low uPRALs (P>0.3). In conclusion, long-term higher calciuria within the physiological range predicts reduced diaphyseal bone mass and bone density particularly in healthy children and adolescents with long-term unfavorable higher dietary acid load, i.e., with lower fruit and vegetable intake., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A distal radius fracture in middle-age and older adults is often considered a sentinel indicator of osteoporosis. Mechanical testing of cadaveric specimens is often used to quantify bone strength and develop insight for relating in-vivo measures to fracture force. Mechanical testing protocols using an intact forearm have been successful at replicating a Colles fracture, however, excised isolated radius protocols based on the intact forearm testing protocol have not been as successful. One protocol originally designed to replicate the physiological condition of a fall on an outstretched hand was reproduced in our laboratory, yet surprisingly the produced distal radius fracture patterns were not consistent among specimens nor was dorsal angulation of the distal fragment that is characteristic of a Colles fracture observed. The purpose of this study was to perform a mechanics-based analysis of the excised radius loading protocol in order to quantify the imposed and internal forces on the radius. An idealized beam model of the excised radius revealed that in the area of the distal radius where Colles fractures occur, 99.99% of the maximum strain on the bone outer surface was the result of pure compressive loading. This loading condition is in direct contrast to the accepted mechanics of a Colles fracture, which is characterized as a metaphyseal bending fracture with the volar cortex failing due to tensile stresses and the dorsal cortex exhibiting compression and comminution. The results suggest that additional research, particularly related to overcoming the difficulties of reliably supporting and applying a force to the distal end of the radius, is necessary for clinical fracture patterns to be reliably reproduced with an excised radius mechanical testing protocol., (Published by Elsevier Ltd.)

Serial reproducibility and reliability critically determine sensitivity to detect changes in response to intervention and provide a basis for sample size estimates. Here, we evaluated the performance of the MRI-based virtual bone biopsy in terms of 26 structural and mechanical parameters in the distal radius of 20 women in the age range of 50 to 75 years (mean=62.0 years, S.D.=8.1 years), representative of typical study populations in drug intervention trials and fracture studies. Subjects were examined three times at average intervals of 20.2 days (S.D.=14.5 days) by MRI at 1.5 T field strength at a voxel size of 137×137×410 μm(3). Methods involved prospective and retrospective 3D image registration and auto-focus motion correction. Analyses were performed from a central 5×5×5 mm(3) cuboid subvolume and trabecular volume consisting of a 13 mm axial slab encompassing the entire medullary cavity. Whole-volume axial stiffness and sub-regional Young's and shear moduli were computed by finite-element analysis. Whole-volume-derived aggregate mean coefficient of variation of all structural parameters was 4.4% (range 1.8% to 7.7%) and 4.0% for axial stiffness; corresponding data in the subvolume were 6.5% (range 1.6% to 13.0%) for structural, and 5.5% (range 4.6% to 6.5%) for mechanical parameters. Aggregate ICC was 0.976 (range 0.947 to 0.986) and 0.992 for whole-volume-derived structural parameters and axial stiffness, and 0.946 (range 0.752 to 0.991) and 0.974 (range 0.965 to 0.978) for subvolume-derived structural and mechanical parameters, respectively. The strongest predictors of whole-volume axial stiffness were BV/TV, junction density, skeleton density and Tb.N (R(2) 0.79-0.87). The same parameters were also highly predictive of sub-regional axial modulus (R(2) 0.88-0.91). The data suggest that the method is suited for longitudinal assessment of the response to therapy. The underlying technology is portable and should be compatible with all general-purpose MRI scanners, which is appealing considering the very large installed base of this modality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The presence of the residual stresses in bone tissue has been noted and the authors have reported that there are residual stresses in bone tissue. The aim of our study is to measure the residual stress distribution in the cortical bone of the extremities of vertebrates and to describe the relationships with the osteon population density. The study used the rabbit limb bones (femur, tibia/fibula, humerus, and radius/ulna) and measured the residual stresses in the bone axial direction at anterior and posterior positions on the cortical surface. The osteons at the sections at the measurement positions were observed by microscopy. As a result, the average stresses at the hindlimb bones and the forelimb bones were 210 and 149 MPa, respectively. In the femur, humerus, and radius/ulna, the residual stresses at the anterior position were larger than those at the posterior position, while in the tibia, the stress at the posterior position was larger than that at the anterior position. Further, in the femur and humerus, the osteon population densities in the anterior positions were larger than those in the posterior positions. In the tibia, the osteon population density in the posterior position was larger than that in the anterior position. Therefore, tensile residual stresses were observed at every measurement position in the rabbit limb bones and the value of residual stress correlated with the osteon population density (r=0.55, P<0.01)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Forearm rotation is an indispensable activity of daily living and comprises complex motions with rotational and translational components. It is thought that changes in these motions with injury or disease may affect diagnostic indices. Several studies have assessed in vivo forearm kinematics with static conditions, but dynamic forearm kinematics have not yet been reported. The purpose of this study was to analyze forearm kinematics during dynamic rotation using radiographic 3D-2D registration methods., Methods: Ten forearms of five healthy males with the mean age of 37 years old were enrolled. Lateral fluoroscopic images were taken during forearm rotation from maximum supination to maximum pronation with their elbows flexed to approximately 45°. Geometric bone models were created from CT scans of the humerus, the radius and the ulna. Three-dimensional kinematics were determined using 3D-2D model registration techniques with the images and models, and the arc of axial rotation of the radius, volar/dorsal translation of the ulna at the distal radioulnar joint and rotation axis of forearm were computed., Findings: The radial rotation arc was 157°. The ulna translated 3.9 mm (SD 1.5mm) dorsally during activity. The rotation axis of the forearm passed through the center of the radial head and the ulnar head at the 1.9 mm (SD 0.7 mm) posterior from its geometric centroid., Interpretation: The posteriorly deviated rotation axis at the ulnar head may result in the ulnar head translating dorsally during pronation. These data provide a basis for objective assessment of pathological forearm function., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The purpose of these analyses was to explore whether physical activity score, leg power or grip strength were associated with tibia and radius estimates of bone strength, cortical density, or total bone area. Peripheral quantitative computed tomography (pQCT) was used to compare tibial and radial bone volumetric density (vBMD, mg/cm(3)), total (ToA, mm(2)) and cortical (CoA, mm(2)) bone area, and estimates of bone compressive strength (bone strength index, BSI) and bending strength (polar strength strain index, SSIp) in a subset (n=1171) of men (> or = 65 years) who participated in the multi-site Osteoporotic Fractures in Men (MrOS) study. Physical activity was assessed by questionnaire (PASE), leg power by Nottingham Power Rig, and grip strength by a hand-held Dynamometer. Participants were categorized into quartiles of PASE, grip strength or leg power. The model was adjusted for age, race, clinic, weight, and limb length. In the tibia, BSI (+7%) and SSIp (+4%) were highest in the most active physically quartile compared to the least active (p<0.05). At the 4% site of the tibia, men with the greatest leg power had both greater ToA (+5%, p<0.001) and BSI (+5.3%, p=0.086) compared to men with the least leg power. At the 66% site of the tibia, the men with the highest leg power, compared to the men with the lowest leg power, had greater ToA (+3%, p=0.045) SSIp (+5%, p=0.008). Similar results were found at both the distal and midshaft of the radius. The findings of this study suggest the importance of maintaining levels of physical activity and muscle strength in older men to prevent bone fragility., (Copyright 2010. Published by Elsevier Inc.)

Severe hyperhomocysteinemia, as seen in classic homocystinuria, is associated with several skeletal malformations and osteopenia. Moreover, hyperhomocysteinemia during pregnancy has been associated with multiple developmental defects in the fetus. This study was undertaken to determine whether offspring of hyperhomocysteinemic mothers have demonstrable changes in bone volume and the epiphyseal growth plate. Ten adult female Sprague-Dawley rats were randomly assigned to the control or experimental group. The experimental group received 100 mg/kg/day of homocysteine in their drinking water for 3 weeks before mating and for the total duration of pregnancy. In each group, three pups per mother were randomly selected. The histomorphometric properties of tibial, radial and vertebral growth plates of newborn rats and the volume fraction of bone were compared between groups. The plasma homocysteine concentration at the end of study was significantly higher in dams in the experimental group (16.42+/-1.5 vs. 4.7+/-1.7 mumol/L, P<0.05). In offspring born to dams given the homocysteine supplement, the volume fraction of bone in the tibia (30.7+/-1.5% vs. 36.8+/-1.9%, P<0.05), radius (29.6+/-1.1% vs. 37.4+/-2%, P<0.05) and vertebra (34.4+/-1.8% vs. 41+/-1.9%, P<0.05) were significantly decreased whereas vertical heights of proliferative (423+/-25.1 vs. 301.8+/-28.1 microm for radius and 131.9+/-5.9 vs. 107.8+/-3.5 microm for vertebra) and hypertrophic zones (213.1+/-12 vs. 163.3+/-7.5 microm for tibia, 153.2+/-7.7 vs. 121.1+/-7.9 microm for radius and 112+/-9.9 vs. 88.4+/-10.1 microm for the vertebra) were increased (P<0.05). The results showed that the administration of homocysteine caused osteopenia in newborn rats. In addition, these data suggest that hyperhomocysteinemia may induce disruption of normal development of epiphyseal cartilage in the rat embryo., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

A major hurdle to surmount in bone-tissue engineering is ensuring a sufficient oxygen supply to newly forming tissue to avoid cell death or delayed development of osteogenic features. We hypothesized that an oxygen-enriched hydrogel scaffold would enhance tissue-engineered bone formation in vivo. To test this, we used a well-characterized mesenchymal stem cell (MSC) line, Tet-off BMP2 MSC, whose cells were engineered to express recombinant human bone morphogenetic protein-2. Cells were suspended in hydrogel supplemented with perfluorotributylamine (PFTBA) and implanted subcutaneously in an ectopic site, a radial bone defect, or a lumbar paravertebral muscle (mouse model of spinal fusion) in C3H/HeN mice. For controls, we used cells suspended in the same gel without PFTBA. In the ectopic site, there were significant increases in bone formation (2.5-fold increase), cell survival, and osteocalcin activity in the PFTBA-supplemented groups. PFTBA supplementation significantly increased structural parameters of bone in radial bone defects and triggered a significant 1.4-fold increase in bone volume in the spinal fusion model. We conclude that synthetic oxygen carrier supplementation of tissue-engineered implants enhances ectopic bone formation and yields better bone quality and volume in bone-repair and spinal fusion models, probably due to increased cell survival.

In our previous study, a three-dimensional zein porous scaffold was prepared. This scaffold showed proper mechanical properties, good biocompatibility, and controllable biodegradation. In addition, it allowed blood vessels to form inside in vivo. In the current study, we prepared the complexes of zein scaffolds and rabbit MSCs, and investigated ectopic bone formation in nude mice. Furthermore, we implanted them into the radius defects of rabbits and assessed whether they could be helpful in the repair of critical-sized bone defects. The results showed that the complexes of zein scaffolds and rabbit MSCs could undergo ectopic bone formation in the thigh muscle pouches of nude mice. More importantly, the complexes could lead to the repair of critical-sized radius defects in rabbits accompanied with blood vessels' formation, which clearly demonstrates promise for the treatment of bone defects through tissue engineering.

Nanocomposite of hydroxyapatite (HAP) surface-grafted with poly(l-lactide) (PLLA) (g-HAP) shows a wide application for bone fixation materials due to its improved interface compatibility, mechanical property and biocompatibility in our previous study. In this paper, a 3-D porous scaffold of g-HAP/poly(lactide-co-glycolide) (PLGA) was fabricated using the solvent casting/particulate leaching method to investigate its applications in bone replacement and tissue engineering. The composite of un-grafted HAP/PLGA and neat PLGA were used as controls. Their in vivo mineralization and osteogenesis were investigated by intramuscular implantation and replacement for repairing radius defects of rabbits. After surface modification, more uniform distribution of g-HAP particles but a lower calcium exposure on the surface of g-HAP/PLGA was observed. Intramuscular implantation study showed that the scaffold of g-HAP/PLGA was more stable than that of PLGA, and exhibited similar mineralization and biodegradability to HAP/PLGA at the 12-20 weeks post-surgery. The implantation study for repairing critical radius defects showed that the scaffold of g-HAP/PLGA exhibited rapid and strong mineralization and osteoconductivity, and the incorporation of BMP-2 could enhance the osteogenic process of the composite implant. The new bone formation with the intact structure of a long bone was guided by the implant of g-HAP/PLGA.

Cyclical intravenous pamidronate is a widely used symptomatic therapy in moderate to severe osteogenesis imperfecta (OI). The effects of treatment discontinuation on long bone development have not been characterized. In this observational study we used peripheral quantitative computed tomography to assess the radius at the distal metaphysis and at the diaphysis in 23 young OI patients (11 female) who had received pamidronate for at least 3 years. Measurements were performed twice, at the time of treatment discontinuation (when the age of the patients ranged from 5.9 to 21.3 years) and at an average of 1.9 years (range 1.5 to 2.4 years) later. At the time of pamidronate discontinuation, all but one of the patients who were below 15 years of age (n=14) had a positive age- and sex-specific z-score for bone mineral content (BMC) at the metaphysis, resulting in a mean z-score of +2.0 (SD=1.0) for this subgroup. In contrast, patients aged 15 years or older (n=9) had an average metaphyseal BMC z-score of -1.5 (SD=1.5). After pamidronate discontinuation, metaphyseal BMC z-score decreased by an average of 2.4 (SD=2.0) in the whole group. The change in BMC z-score was growth-dependent, as BMC z-scores decreased by about 2 or more in all patients in whom distal radius growth plates were open when pamidronate was discontinued. In contrast, none of the 11 patients with closed distal radius growth plates experienced a decrease in metaphyseal BMC z-score by more than 2. At the diaphysis, the average BMC z-score was low at the time of the last pamidronate infusion [z-score -1.7 (SD=1.4)]. After pamidronate discontinuation, the average diaphyseal BMC z-score decreased by only 0.3 (SD=0.4). In summary, this study shows that the effect of pamidronate discontinuation is much larger at the radial metaphysis than at the diaphysis and is dependent on growth. Metaphyseal bone tissue added by longitudinal growth after treatment discontinuation has a lower density than tissue created during treatment. It is possible that this produces zones of localized bone fragility after pamidronate treatment is stopped in growing children.

Children and adolescents with osteogenesis imperfecta (OI) generally have low bone mineral density (BMD) at the lumbar spine and hip. However, the effects of the disease on diaphyseal bone have not been well characterized, even though long-bone fractures are common in such patients. In this study on 42 fully mobile children and adolescents with mild OI (age 6-19 years; 17 girls), lumbar spine, radius (metaphysis and diaphysis) and second metacarpal (diaphysis) were analyzed using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography and radiogrammetry, respectively. Bone mineral content at the lumbar spine, radial metaphysis and radial diaphysis was between 25% and 31% lower than in age-matched healthy children and adolescents. At the lumbar spine and radial metaphysis, bone size (as estimated from projection area and cross-sectional area, respectively) was normal or only slightly below the results expected for healthy individuals, whereas bone size was very small at the diaphyseal sites of the radius and the second metacarpal. Total volumetric BMD is defined as the ratio between bone mineral content and bone volume. Therefore, these differences in bone size between skeletal locations led to markedly discrepant results for total volumetric BMD. Total volumetric BMD was low at the lumbar spine (23% below result expected for healthy subjects of the same age) and the radial metaphysis (-15%) but elevated at the radial diaphysis (+25%; all differences to controls significant at P < 0.001). Despite high volumetric BMD, estimated bending strength at the radial diaphysis was very low. These results demonstrate that volumetric BMD can be abnormally high and low within the same bone in the same individual and highlight the fact that volumetric BMD at diaphyseal sites does not provide a good estimate of bone strength when bone size is abnormal.

Muscle atrophy and bone loss pose substantial problems for long-term space flight and in clinical immobilization. We therefore tested the efficacy of flywheel resistive exercise and pamidronate to counteract such losses. Twenty five young healthy males underwent strict bed rest with -6 degrees head-down tilt for 90 days. Subjects were randomized into an exercise group that practiced resistive exercise with a 'flywheel' (FW) device every 2-3 days, a pamidronate group (Pam) that received 60 mg pamidronate i.v. 14 days prior to bed rest and a control group (Ctrl) that received none of these countermeasures. During the study, Ca(++) and protein intake were controlled. Peripheral quantitative computed tomography (pQCT) was used to assess bone mineral content (BMC) and muscle cross sectional area (mCSA) of calf and forearm. Measurements were taken twice during baseline data collection, after 28 and after 89 days bed rest, and after 14 days recovery. On the same days, urinary Pyridinoline excretion and serum levels of alkaline phosphatase, Ca(++) and PTH were measured. Pre-study exercise habits were assessed through the Freiburg questionnaire. Losses in calf mCSA were significantly reduced in FW (Ctrl: -25.6% +/- 2.5% Pam: -25.6% +/- 3.7%, FW: -17.3% +/- 2.7%), but not in the forearm mCSA (Ctrl: -6.4% +/- 4.33%, Pam: -7.7% +/- 4.1%, FW: -7.6% +/- 3.3%). Both diaphyseal and epiphyseal BMC losses of the tibia were mitigated in Pam and FW as compared to Ctrl, although this was significant only at the diaphysis. Inter-individual variability was significantly greater for changes in BMC than in mCSA, and correlation of BMC losses was poor among different locations of the tibia. A significant positive correlation was found between change in tibia epiphyseal BMC and serum cortisol levels. These findings suggest that both countermeasures are only partly effective to preserve BMC (FW and Pam) and mCSA (FW) of the lower leg during bed rest. The partial efficacy of flywheel exercise as well as the bones' response to unloading per se underlines the importance of mechanical stimuli. The huge variability of BMC changes, however, suggests that other factors affect changes in whole-bone strength following acute mechanical disuse.

Metabolic bone diseases such as osteoporosis usually cause a decrease in bone mass and a deterioration of bone microarchitecture leading to a decline in bone strength. Methods to predict bone strength in patients are currently based on bone mass only. It has been suggested that an improved prediction of bone strength might be possible if structural changes are taken into account as well. In this study we evaluated which structural parameters (other than bone mass) are the best predictors for changes in bone mechanical properties of the human radius after different bone atrophy scenarios and whether the original strength of the affected bone can be recovered if bone loss is restored by thickening of the remaining structures. To answer these questions, a human radius was measured with a microcomputer tomography scanner to extract the full three-dimensional architecture of the distal radius at an isotropic resolution of 80 microm. Eight models with modified bone architecture were created and the mechanical variations due to these modifications were studied using microfinite element (micro-FE) simulations. In four models mass was lowered by 20%, either by reducing cortical thickness, trabecular thickness, or number of trabeculae or by overall thinning of structures. In the other four models bone mass was restored to the original value using a trabecular bone thickening procedure. The micro-FE analyses revealed that most load was carried by the cortical bone. For this reason, bone strength was affected most in the reduced cortical thickness model. For the same reason, the trabecular bone atrophy scenarios, all of which affected bone strength in a very similar way, resulted in less dramatic bone strength reduction. The restoration of bone mass did not recover the original bone strength. These findings demonstrate that the importance of different parameters for the prediction of bone strength also depends on the mechanical loading. This could explain why results of earlier studies on the importance of structural parameters can be inconsistent and site-dependent.

Objective: The purpose of this study was to determine the effect of radial head fracture size on radiocapitellar stability., Design: Repeated measures using Instron materials testing machine., Background: Radial head fractures are common injuries and controversy exists as to the optimal management of displaced wedge fractures., Methods: Fractures were simulated in six fresh-frozen cadaveric radiocapitellar joints by removing sequential 20 degree wedges from the anterolateral aspect of each radial head until 140 degrees of the radial head was removed. Decreased shear load at the radial head during joint loading was used as an indicator of decreased stability at the radiocapitellar joint. Using a custom designed jig and employing a compressive joint load of 100 N, the maximum shear load at the radiocapitellar joint was measured at 30, 60, 90 and 120 degrees of elbow flexion., Results: There was no difference in the shear load between the intact specimen and that with a 20 degree wedge removed at all flexion angles (P>0.05). Shear load decreased with each increase in wedge size between 20 and 120 degrees (P<0.05). After 120 degrees, one-third the diameter of the radial head, the shear load was always less than 0.8 N., Conclusions: This study demonstrated an inverse relationship between radiocapitellar joint stability and radial head fracture size., Relevance: Small radial head fracture fragments are biomechanically significant. Therefore, the use of an arbitrary fragment size as an indication for surgery should be reconsidered, particularly if there is an associated ligamentous injury.

Biocompatibility of two calcium phosphate cements (CPCs), reinforced with phosphorylated chitosan (P-chitosan), was investigated in rabbits in present study. The two CPCs are monocalcium phosphate monohydrate (MPCM) with calcium oxide (CaO) in 1 M phosphate buffer (i.e. MCPM/CaO/1 M phosphate buffer cement, CPC-I) and dicalcium phosphate dihydrate (DCPD) with calcium hydroxide [Ca(OH)2] in 1 M Na2HPO4 solution (i.e. DCPD/Ca(OH)2/1 M Na2HPO4 cement, CPC-II). Different amount of P-chitosan was added to the liquid phase before the power phase was mixed with the liquid phase. The MCPM/CaO/1 M phosphate buffer/P-chitosan cements (P-CPC-I) with neutral pH were filled into the holey defects of rabbit tibias. While the DCPD/Ca(OH)2/1 M Na2HPO4/P-chitosan cements (P-CPC-II) shaped as prehardened cylinders were implanted into rabbit radial defects. After operation, the two serial groups and CPC-II controls were observed for 1, 4, 12 and 22 weeks, respectively. Histological and histomorphological studies proved that P-chitosan containing cements are biocompatible, bioabsorbable and osteoinductive. The biodegradation rate has a negative relationship with the P-chitosan content. Progressive substitution took place at the interface of implants and host bones. No adverse effects were found in tissues around the bone defects. Thus, they could be used as bone substitutes in clinic.

There is increasing evidence that, in addition to bone mass, bone microarchitecture and its mechanical load distribution are important factors for the determination of bone strength. Recently, it has been shown that new high-resolution imaging techniques in combination with new modeling algorithms based on the finite element (FE) method can account for these additional factors. Such models thus could provide more relevant information for the estimation of bone failure load. The purpose of the present study was to determine whether results of whole-bone micro-FE (microFE) analyses with models based on three-dimensional peripheral quantitative computer tomography (3D-pQCT) images (isotropic voxel resolution of 165 microm) could predict the failure load of the human radius more accurately than results with dual-energy X-ray absorptiometry (DXA) or bone morphology measurements. For this purpose, microFE models were created using 54 embalmed cadaver arms. It was assumed that bone failure would be initiated if a certain percentage of the bone tissue (varied from 1% to 7%) would be strained beyond the tissue yield strain. The external force that produced this tissue strain was calculated from the FE analyses. These predictions were correlated with results of real compression testing on the same cadaver arms. The results of these compression tests were also correlated with results of DXA and structural measurements of these arms. The compression tests produced Colles-type fractures in the distal 4 cm of the radius. The predicted failure loads calculated from the FE analysis agreed well with those measured in the experiments (R(2) = 0.75 p < 0.001). Lower correlations were found with bone mass (R(2) = 0.48, p < 0.001) and bone structural parameters (R(2) = 0.57 p < 0.001). We conclude that application of the techniques investigated here can lead to a better prediction of the bone failure load for bone in vivo than is possible from DXA measurements, structural parameters, or a combination thereof.

The purpose of this case-control study was to determine bone mineral content and areal bone mineral density at various skeletal sites in former preterm girls, aged 7-9 years, and to compare these data with age-matched term controls. Subjects included 25 white, prepubertal, former preterm girls (gestational age 30.8 +/- 0.3 weeks, birthweight 1461 +/- 56 g [mean +/- SEM]). Controls included 50 healthy, white, prepubertal girls born at term and matched for age (two controls per case). Measurements included anthropometric variables, calcium intake according to a food-frequency questionnaire, bone mineral content (BMC; grams), and areal bone mineral density (aBMD; grams per square centimeter), using dual-energy X-ray absorptiometry (DXA) at six skeletal sites. Thirteen preterm girls and 13 age-matched term controls were reassessed 1 year after the first DXA measurement. The former preterm girls were similar to controls in terms of age and height, but were lighter (24.6 +/- 0.6 vs. 27.0 +/- 0.6 kg, p = 0.02). They also reported a higher median calcium intake (1058 vs. 759 mg/day, p = 0.004). aBMD was lower in former preterms compared with controls at the level of the radial metaphysis (0.283 +/- 0.006 vs. 0.298 +/- 0.004, p = 0.04), femoral neck (0.593 +/- 0.011 vs. 0.638 +/- 0.010, p = 0.007), and total hip (0.596 +/- 0.012 vs. 0.640 +/- 0.010, p = 0.007), but was similar between the two groups at the radial diaphysis (0.437 +/- 0.004 vs. 0.436 +/- 0.004) and femoral diaphysis (1.026 +/- 0.015 vs. 1.030 +/- 0.011). Femoral neck aBMD remained lower compared with controls in the subgroup of preterm girls reassessed after 1 year (0.608 +/- 0.017 vs. 0.672 +/- 0.020, p = 0.02). In random effects models for longitudinal data, taking into account the effects of age, weight, and height on aBMD (dependent variable), femoral neck aBMD remained lower in former preterms (p < 0.001). Prepubertal former preterm girls showed growth recovery, but had lower aBMD at the hip and radial metaphysis than age-matched term controls, despite spontaneously higher calcium intake. Preterm girls had similar aBMD results compared with controls at sites with predominantly cortical bone (radial and femoral diaphysis), which are known to be more sensitive to calcium intake.

A key feature of postmenopausal osteoporosis is the loss of trabecular bone mass and connectivity. The current study focuses on these parameters in the assessment of long-term (12 and 18 months) parathyroid hormone (PTH) therapy and its withdrawal (6 months) in the ovariectomized cynomolgus monkey (Macaca fascicularis), a well-characterized model for bone changes associated with postmenopausal osteoporosis. We used static and dynamic histomorphometric parameters to assess the amount and architecture of cancellous bone in four clinically important sites for osteoporotic fractures, including the lumbar vertebra, femoral neck, distal radius, and iliac crest. Recombinant human PTH(1-34) was administered daily to two groups for 18 months at 1.0 microg/kg per day (n = 19) and 5.0 microg/kg per day (n = 21). To study the effects of PTH withdrawal, two groups were administered PTH(1-34) daily for 12 months at 1.0 microg/kg per day (n = 20) and 5.0 microg/kg per day (n = 20), followed by daily administration of vehicle for 6 months. Sham-ovariectomized and ovariectomized (ovx) groups each received daily injections of vehicle for 18 months. Treatment with PTH had minimal effects on bone formation rates at the timepoints studied, but markedly increased cancellous bone volume relative to ovx monkeys in iliac crest biopsies at 6 and 15 months, as well as in terminal specimens of lumbar vertebrae, femoral neck, and distal radius after 18 months. At all sites, PTH significantly improved trabecular architecture, as evidenced by increased trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp), with no significant change in trabecular thickness (Tb.Th). The mechanism of these structural changes is suggested by qualitative observations of trabecular tunneling observed in the iliac crest and vertebra. Longitudinal tunneling of thickened individual trabeculae is hypothesized to convert them into multiple trabeculae, resulting in a normalization of Tb.Th, but an increase in Tb.N. A significant positive effect on cancellous bone volume was still apparent after a 3-6 month withdrawal period following 12 months of PTH treatment in the iliac crest, vertebra, and femoral neck. Corresponding increases in Tb.N and decreases in Tb.Sp also remained significant after PTH withdrawal at these three sites. The distal radius was relatively insensitive to PTH treatment or its withdrawal, compared with the other bones. In summary, PTH therapy dramatically improved cancellous bone mass and architecture in both axial and appendicular sites.

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.

The mechanical properties of cancellous bone have been shown to depend on bone density and on the anisotropy of the trabecular bone structure. By means of high-resolution quantitative computed tomography (QCT), providing a nominal resolution of 0.17 mm, it became possible to assess both apparent density and trabecular microstructure of intact bones. In order to study the influence of age- and disease-related bone loss on the mechanical properties of cancellous bone, a more phenomenological approach was used to develop a novel bone resorption algorithm, called simulated bone atrophy. The algorithm, which is principally based on constrained Gauss filtration of segmented data volumes, was applied to create derived microstructural models. The mechanical behavior of the cancellous bone can be expressed as a function of the anisotropic bone properties of the microstructural model on the continuum level. To study the influence of bone atrophy on bone strength we compared three models: the originally noninvasively measured bone biopsy and two derived models simulating moderate and pronounced atrophy. For the comparison of the three models, the apparent Young's moduli in the three orthogonal directions were predicted for each model with the help of three-dimensional finite-element analysis. Realistic results for the apparent Young's moduli were found for the tissue moduli chosen. The results suggest that the prediction of anisotropic material properties of cancellous bone based on noninvasive measurements of trabecular microstructures and the application of simulated bone atrophy may be helpful to understand the influence of age- and disease-related bone loss on bone strength.

Sodium fluoride has for more than 2 decades been a commonly used therapeutic agent for established osteoporosis because of a repeatedly documented anabolic effect on trabecular bone mass. Recently, however, three controlled trials have failed to demonstrate any therapeutic advantage of NaF over placebo with respect to vertebral fracture rate. Also, there have been several reports of an increased incidence of nonvertebral fractures during fluoride administration. Thus, the efficacy of fluoride therapy remains a controversial issue. The aim of this longitudinal study was to investigate the effect of sodium fluoride (40-60 mg per day), calcium (45 mmol), and vitamin D2 (18,000 IU) on trabecular bone strength, assessed before and after 1 or 5 years of treatment for osteoporosis. Iliac crest biopsies were taken before and after 1 year of treatment in 12 patients, and before and after 5 years of treatment in 14 patients. Measurements were made of biomechanical competence, ash content, and bone fluoride content, and bone strength parameters were normalized for ash content, thereby obtaining a measure of trabecular bone quality. Bone fluoride content was significantly increased after both 1 and 5 years of treatment, indicating that the administered fluoride had been ingested. After 1 year of treatment, no difference was observed in iliac crest trabecular bone ash content. A general trend for decreased bone strength and bone quality was observed, but this was insignificant. After 5 years of fluoride treatment, an insignificant decrease in iliac crest trabecular bone ash content was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential for the recovery of bone lost during the active phase of disuse osteoporosis, both in the diaphyseal compacta and metaphyseal spongiosa was tested in young adult and old Beagle dogs. Immobilization for up to 60 weeks was achieved by placing the forelimb in a spica cast and remobilization by removing it. Bone volume was estimated in the third metacarpus, radius, ulna and humerus at the mid-diaphysis and at the level of distal metaphyseal spongiosa in both forelimbs by radiography and histomorphometry. Measurements carried out on animals remobilized showed considerable recovery of the original bone loss. In both age groups, the residual deficits increased, however, with the duration of immobilization and were similar in the metaphyseal spongiosa and in the diaphyseal compacta. The old dogs which began the study with 10% less bone than the younger dogs, showed smaller proportional losses than the younger dogs but greater residual deficits, most evident in the diaphysis. In both age groups the distal, weight-bearing bones tended to show greater losses and also greater recovery both in diaphyseal compacta and the metaphyseal spongiosa. Thus, 28 weeks after cast removal following 32 weeks of immobilization the following findings were noted: In the third metacarpal diaphyseal compacta in the younger dogs, a 53.6% loss (mostly from the periosteal envelope) decreased to 16.3% (a 70% recovery) while in the older dogs a 37.6% loss (mostly from the endosteal envelope) decreased to 23% (a 40% recovery).(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to evaluate the representativity of iliac crest biopsy for the amount of mineralized trabecular and cortical bone in the skeleton. The following data were obtained on bone from 14 necropsies: right sided iliac crest biopsy, lumbar spine biopsy, dry fat free weight of lumbar spine, bone mineral density (BMD) in the lumbar spine and dry fat free weight of cortical and trabecular bone from the left distal forearm. The amount of mineralized cortical and trabecular bone from various sites was compared by linear regression analysis. The results confirm iliac crest biopsy as a good predictor of the amount of trabecular bone, but not of cortical bone. Furthermore, iliac crest biopsy is a better estimate of the amount of trabecular bone in the lumbar spine than spinal BMD.