High‐resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a newly developed in vivo clinical imaging modality. It can assess the 3D microstructure of cortical and trabecular bone at the distal radius and tibia and is suitable as an input for microstructural finite element (µFE) analysis to evaluate bone's mechanical competence. In order for microstructural and image‐based µFE analyses to become standard clinical tools, validation with a current gold standard, namely, high‐resolution micro‐computed tomography (µCT), is required. Microstructural measurements of 19 human cadaveric distal tibiae were performed for the registered HR‐pQCT and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both HR‐pQCT and µCT images were determined by µFE analysis. The standard HR‐pQCT patient protocol measurements, derived bone volume fraction (BV/TV^d), trabecular number (Tb.N*), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and cortical thickness (Ct.Th), as well as the voxel‐based direct measurements, BV/TV, Tb.N*, Tb.Th*, Tb.Sp*, Ct.Th, bone surface‐to‐volume ratio (BS/BV), structure model index (SMI), and connectivity density (Conn.D), correlated well with their respective gold standards, and both contributed to µFE‐predicted mechanical properties in either single or multiple linear regressions. The mechanical measurements, although overestimated by HR‐pQCT, correlated highly with their gold standards. Moreover, elastic moduli of cubic subvolumes of trabecular bone predicted whole bone or trabecular bone stiffness in distal tibia. We conclude that microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR‐pQCT images and provide additional information regarding bone fragility. © 2010 American Society for Bone and Mineral Research     

Interindividual and intraspecimen variability of 3-D bone microarchitectural parameters in iliac crest biopsies imaged by conventional micro-computed tomography

Bone microarchitecture of the iliac bone is used to characterize the properties of bone tissue in osteoporosis, particularly in pharmacological studies. Trabecular bone is known to be heterogeneous media. For a few years, the analysis of three-dimensional (3-D) bone microarchitecture has been based on micro-computed tomography (micro-CT). To assess the interindividual variability (inter-indVar) and the intrasample variability (intra-sampVar) of iliac crest biopsies, we used a Bordier needle trephine in 35 postmenopausal female cadavers (mean age, 74.4 +/- 10.4 years). Finally, we had at our disposal 32 individual iliac crests to assess the inter-indVar and 21 oriented specimens to assess the intra-sampVar. All the samples were chemically defatted, and the images were performed with a desktop micro-CT with a voxel size of 10.77 mum. We measured trabecular bone parameters: bone volume/tissue volume (BV/TV %), trabecular thickness and spacing (Tb. Th*, Tb.Sp* mum), bone surface/bone volume (BS/BV, 1/mm), the trabecular number (Tb.N, 1/mm), structure model index (SMI), trabecular pattern factor (Tb.Pf), and degree of anisotropy (DA). We also measured cortical bone parameters: cortical thickness (Cort.Th), porosity (PoV/TV), and pore diameter (Po.Dm). For the inter-indVar, we analyzed a fixed volume of interest corresponding to 119.8 mm(3) centered on each iliac crest. To assess the intra-sampVar, we divided the whole trabecular volume into three equal height parts (external, middle, internal). BV/TV, Tb.N, and PoV/TV were negatively correlated with age and Tb.Sp* and SMI were positively correlated. The mean difference of absolute individual variations in percentage with the middle area used as a reference, comparatively to external and internal areas, ranged from 6.6% (Tb.Sp*) to 27.8% (BV/TV), except Tb.Pf, which showed large variability. There was no difference between external and internal areas, with a tendency for lower values of BV/TV, Tb.Th*, and Tb.N in the middle of the iliac crest and higher values of Tb.Sp* and BS/BV. The evaluation of bone microarchitecture of iliac crest samples on micro-CT images is reliable. The heterogeneity of bone inside the iliac crest is noticeable as leading to analyzing the largest possible quantity of bone, with standardized location, according to cortex but without any assumption of orientation.     

Side-to-side and within-side variability of 3D bone microarchitecture by conventional micro-computed tomography of paired iliac crest biopsies

Bone microarchitecture in osteoporosis can be characterized by examining iliac bone biopsies and treatment effects assessed by comparing a baseline biopsy from one side to a posttreatment biopsy from the other side, a method that assumes limited side-to-side variability. New techniques based on micro-computed tomography (microCT) provide information on the three-dimensional (3D) microarchitecture of bone. We used microCT to measure side-to-side and within-side variability of 3D microarchitectural parameters of trabecular and cortical bone in paired iliac-crest biopsies, one from each side. A Bordier needle trephine was used to collect biopsies from 30 postmenopausal female cadavers (mean age, 73.7+/-10.7 years; range, 55-96 years). Biopsies were chemically defatted then imaged using a desktop microCT scanner (voxel size, 10.77 microm). Parameters measured in trabecular bone consisted of bone volume/tissue volume (BV/TV, %), direct trabecular thickness and trabecular spacing (Tb.Th and Tb.Sp, microm) using the sphere method, bone surface/bone volume (BS/BV, mm(-1)), trabecular number (Tb.N, mm(-1)), structure model index (SMI), trabecular pattern factor (Tb.Pf), and degree of anisotropy (DA). In cortical bone, we measured cortical thickness (Cort.Th), porosity (Cort.Porosity), and pore diameter (Po.Dm). For trabecular bone parameters, reproducibility as assessed from two microCT acquisitions ranged from 4.1% to 6.9%. To assess side-to-side variability, we matched the volumes of interest selected in the right and left iliac crests. The mean difference in absolute individual percent variation (mAbsDelta(ind)) between the two sides ranged from 10.8% to 14.8% for all trabecular parameters except Tb.Pf (74%) and SMI (84%). In cortical bone, mAbsDelta(ind) were 11.6% for Po.Dm, 15.1% for Cort.Porosity, and 27.6% for Cort.Th. To assess within-side variability, we divided the trabecular iliac crest volume into three equal parts, one adjacent to each cortex and one in the middle. Values of mAbsDelta(ind) versus the middle part were ranging from 7.6% for Tb.Sp to 26.2% for BV/TV. Thus, within-side variability was similar in magnitude to side-to-side variability. The considerable differences in robustness across trabecular parameters indicate a need for selecting the most stable parameters, most notably for longitudinal studies of small numbers of patients. Acquisition by microCT and image analysis must comply with stringent quality criteria, especially the distance from the cortices must be standardized.     

A comparison of bone quality at the distal radius between Asian and white adolescents and young adults: An HR‐pQCT study

Paradoxically, Asians have lower areal bone mineral density (aBMD), but their rates of hip and wrist fractures are lower than whites. Therefore, we used high‐resolution pQCT (HR‐pQCT) to determine whether differences in bone macrostructure and microstructure, BMD, and bone strength at the distal radius were apparent in Asian (n = 91, 53 males, 38 females, [mean ± SD] 17.3 ± 1.5 years) and white (n = 89, 46 males, 43 females, 18.1 ± 1.8 years) adolescents and young adults. HR‐pQCT outcomes included total BMD (Tt.BMD), trabecular bone volume fraction (BV/TV), and trabecular number (Tb.N), thickness (Tb.Th), and separation (Tb.Sp). We used an automated segmentation algorithm to determine total bone area (Tt.Ar), and cortical BMD (Ct.BMD), porosity (Ct.Po), and thickness (Ct.Th), and we applied finite element (FE) analysis to HR‐pQCT scans to estimate bone strength. We fit sex‐specific multivariable regression models to compare bone outcomes between Asians and whites, adjusting for age, age at menarche (girls), lean mass, ulnar length, dietary calcium intake, and physical activity. In males, after adjusting for covariates, Asians had 11% greater Tt.BMD, 8% greater Ct.BMD, and 25% lower Ct.Po than whites (p < 0.05). Also, Asians had 9% smaller Tt.Ar and 27% greater Ct.Th (p < 0.01). In females, Asians had smaller Tt.Ar than whites (16%, p < 0.001), but this difference was not significant after adjusting for covariates. Asian females had 5% greater Ct.BMD, 12% greater Ct.Th, and 11% lower Tb.Sp than whites after adjusting for covariates (p < 0.05). Estimated bone strength did not differ between Asian and white males or females. Our study supports the notion of compensatory elements of bone structure that sustain bone strength; smaller bones as observed between those of Asian origin compared with white origin have, on average, more dense, less porous, and thicker cortices. Longitudinal studies are needed to determine whether ethnic differences in bone structure exist in childhood, persist into old age, and whether they influence fracture risk.     

Patient-specific microarchitecture of vertebral cancellous bone: a peripheral quantitative computed tomographic and histological study

This study directly compares peripheral quantitative computed tomography (pQCT) and histology for the assessment of 11 morphological parameters. Sixty-eight cylindrical cancellous bone samples were cored from the thoracic (T-9) thoracolumbar (T-12 or L-1), and lumbar (L-4) vertebral bodies of nine autopsy subjects (aged 44–88 years). Four transverse slices were acquired by pQCT from the bottom to the top of each cylinder. Slice thickness was 300 μm and pixel size was 70 × 70 μm. Thin sections (5 μm) were obtained at the same location in the samples, stained with Von Kossa, and photographed. Classical morphological parameters and strut analysis parameters were measured on all images (272 pQCT and 272 matched histological sections). Because of the partial volume effect and specific thresholding procedure, pQCT overestimated the absolute value of the bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) by a factor 2. The trabecular number (Tb.N), trabecular spacing (Tb.Sp), and total strut length (TSL) were correctly estimated. However, the direct correlation between pQCT and histology was excellent (r² > 0.85, p < 0.001) for BV/TV, Tb.N, Tb.Sp, TSL, and star surface. For Tb.Th, number of nodes, and number of free ends, the correlation was also good (r² > 0.6, p < 0.001). Using a random regression model, we also explored the ability of these parameters to add structural information to the readily available BV/TV or apparent density. The model identified significant (p < 0.001) differences between subjects. For a given BV/TV, some patients had more trabeculae (Tb.N) that were thinner (Tb.Th) and more disconnected (higher free ends and star). This was observed for both histology and pQCT morphometrical data. Our analysis demonstrates the capacity of both histology and pQCT to detect subjects with specific structural patterns in vertebral cancellous bone.     

Micro‐computed tomography evaluation of vertebral end‐plate trabecular bone changes in a porcine asymmetric vertebral tether

We conducted a micro‐CT analysis of subchondral bone of the vertebral end‐plates after application of compressive stress. Thoracic and lumbar vertebral units were instrumented by carrying out left asymmetric tether in eleven 4‐week‐old pigs. After 3 months of growth, instrumented units and control units were harvested. Micro‐CT study of subchondral bone was performed on one central and two lateral specimens (fixated side and non‐fixated side). In control units, bone volume fraction (BV/TV), number of trabeculae (Tb.N), trabecular thickness (Tb.Th), and degree of anisotropy (DA) were significantly higher, whereas intertrabecular space (Tb.Sp) was significantly lower in center than in periphery. No significant difference between the fixated and non‐fixated sides was found. In instrumented units, BV/TV, Tb.N, Tb.Th, and DA were significantly higher in center than in periphery. BV/TV, Tb.N, and Conn.D were significantly higher in fixated than in non‐fixated side, while Tb.Sp was significantly lower. We noted BV/TV, Tb.N, and Tb.Th significantly lower, and Tb.Sp significantly higher, in the instrumented levels. This study showed, in instrumented units, two opposing processes generating a reorganization of the trabecular network. First, an osteolytic process (decrease in BV/TV, Tb.N, Tb.Th) by stress‐shielding, greater in center and on non‐fixated side. Second, an osteogenic process (higher BV/TV, Tb.N, Conn.D, and lower Tb.Sp) due to the compressive loading induced by growth on the fixated side. This study demonstrates the densification of the trabecular bone tissue of the vertebral end‐plates after compressive loading, and illustrates the potential risks of excessively rigid spinal instrumentation which may induce premature osteopenia. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:232–240, 2010     

Relationships between bone structure in the iliac crest and bone structure and strength in the lumbar spine

The purpose of this study was to examine the relationship between histomorphometric variables of cancellous bone structure and ultimate compressive strength (UCS) in the second lumbar vertebra (L2) and to determine whether structural variables in the iliac crest are predictive of the same variables and of UCS in L2. At autopsy, 7.5 mm diameter cores were removed from the iliac crest and from L2 of 29 subjects who had died suddenly without bone disease. Cancellous bone volume (BV/TV, %) was significantly lower in L2 than in iliac crest due to lower trabecular number (Tb.N, per mm) and thickness (Tb.Th, µm). There were significant correlations between iliac crest and L2 for BV/TV, Tb.N and trabecular separation (Tb.Sp, µm), but not for Tb.Th. BV/TV was negatively correlated, and Tb.Sp was positively correlated with age at both sites. Tb.Th was not significantly correlated with age in the iliac crest, but a significant negative correlation was observed in L2. The UCS of vertebral cores was negatively correlated with age. BV/TV and Tb.Th in L2 were positively correlated with UCS in L2. Cortical width and BV/TV in iliac crest were positively correlated with UCS in L2. We conclude that: (1) cancellous bone volume in the iliac crest is higher than in the lumbar spine due to thicker, more closely spaced trabecular plates, (2) the changes in structural variables with age are generally similar in the iliac crest and lumbar vertebra, but trabecular thinning with age is more evident in the spine than in the ilium, and (3) the compressive strength of cancellous bone in the lumbar spine is correlated with histomorphometric variables of bone structure, as measured both in the lumbar spine and in the iliac crest.     

Abdominal Aortic Calcification,BMD, and Bone Microstructure: A Population‐Based Study

To better define the relationship between vascular calcification and bone mass/structure, we assessed abdominal aortic calcification (AAC), BMD, and bone microstructure in an age‐stratified, random sample of 693 Rochester, MN, residents. Participants underwent QCT of the spine and hip and high‐resolution pQCT (HRpQCT) of the radius to define volumetric BMD (vBMD) and microstructural parameters. AAC was quantified with the Agatston scoring method. In men, AAC correlated with lower vertebral trabecular and femoral neck vBMD (p < 0.001), but not after age or multivariable (age, body mass index, smoking status) adjustment. Separation into <50 and ≥50 yr showed this pattern only in the older men. BV/TV and Tb.Th inversely correlated with AAC in all men (p < 0.001), and Tb.Th remained significantly correlated after age adjustment (p < 0.05). Tb.N positively correlated with AAC in younger men (p < 0.001) but negatively correlated in older men (p < 0.001). The opposite was true with Tb.Sp (p = 0.01 and p < 0.001, respectively). Lower Tb.N and higher Tb.Sp correlated with AAC in older men even after multivariable adjustment. Among all women and postmenopausal women, AAC correlated with lower vertebral and femoral neck vBMD (p < 0.001) but not after adjustment. Lower BV/TV and Tb.Th correlated with AAC (p = 0.03 and p = 0.04, respectively) in women, but not after adjustment. Our findings support an age‐dependent association between AAC and vBMD. We also found that AAC correlates with specific bone microstructural parameters in older men, suggesting a possible common pathogenesis for vascular calcification and deterioration in bone structure. However, sex‐specific differences exist.     

Trabecular architecture in iliac crest bone biopsies: infra-individual variability in structural parameters and changes with age

A histomorphometric study was conducted on bilateral iliac crest samples obtained at autopsy from 27 subjects who had died suddenly. Six parameters related to cancellous bone structure were measured: bone volume (BV/TV), surface density (BS/TV), surface/volume ratio (BS/BV), trabecular thickness (Tb.Th.), trabecular number (Tb.N), and trabecular separation (Tb.Sp). There were no significant differences between right and left sides in the mean values for each parameter. However, when subjects were considered individually, there was a substantial difference in the majority of cases for all parameters. The intra-individual variation (IIV) was calculated for each subject as the percentage deviation from the mean for the two sides. There was a wide range in IIV (0.05-30.27%) with a mean value of approximately 11.5% for each parameter. In males the mean IIV ranged from 9 to 11% and from 14 to 16% in females. The IIV in BV/TV was positively correlated with age. Data generated on a subsample of 15 males were used to predict patient group sizes required to detect minimum significant differences in studies involving repeat biopsies. Sample sizes of 32, 16, and 8 patients would be required for relative increments in BV/TV of 29, 36, and 46%, respectively, to be statistically significant. Tb.Sp increased significantly with age but there was no significant change in Tb.Th. This supports the view that bone loss with aging occurs primarily through a mechanism involving complete disappearance of individual trabecular plates.     

Microarchitecture of the Radial Head and Its Changes in Aging

Fractures of the radial head are common; however, it remains to be determined whether the radial head has to be considered as a typical location for fractures associated with osteoporosis. To investigate whether the human radial head shows structural changes during aging, we analyzed 30 left and 30 right human radial heads taken from 30 individuals. The specimens taken from the left side were analyzed by peripheral quantitative computed tomography (pQCT) and micro-CT. The specimens taken from the right elbow joint were analyzed by radiography and histomorphometry. In these specimens pQCT revealed a significant decrease of total and cortical bone mineral density (BMD_to BMD_co) with aging, regardless of sex. Histomorphometry revealed a significant reduction of cortical thickness (Ct.Th), bone volume per tissue volume (BV/TV), and trabecular thickness (Tb.Th) in male and female specimens. In this context, mean BV/TV and mean trabecular number (Tb.N) values were significantly lower and, accordingly, mean trabecular separation (Tb.Sp) was significantly higher in female samples. The presented study demonstrates that the radial head is a skeletal site where different age- and sex-related changes of the bone structure become manifest. These microarchitectural changes might contribute to the pathogenesis of radial head fractures, especially in aged female patients where trabecular parameters (BMD_tr and Tb.Sp) change significantly for the worse compared to male patients.     

Brazilian normal static bone histomorphometry: effects of age,sex, and race

Bone histomorphometry values for normal individuals within different populations have been well established. We studied iliac crest bone samples from 125 healthy Brazilian subjects. The effect of sex, race, and age variables on histomorphometric parameters was evaluated. Bone volume showed a trend to decrease with age in both sexes, being significantly higher in black females and Caucasian males. Interactions among sex, race, and age had no effect on trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). However, age had a significant effect on Tb.Th and Tb.Sp, and sex had an impact on Tb.Sp. Trabecular number (Tb.N) was higher in black females than in males and was higher in Asian males than in females. Among females, Tb.N was lower in Asians than in other races and was higher in blacks than in Caucasians and or in those of mulattos. In addition, Tb.N was higher in males under 10 than in males over 50 years old, was higher in females under 10 than in females in any other age bracket, and was lower in females in the 41–50 age bracket than in younger females. Osteoid volume and osteoid surface were significantly higher in males than in females, and a significant age-related difference in osteoid thickness was observed. No significant sex-related or race-related differences were found in terms of resorption, although eroded surface decreased with age. In conclusion, sex, race, and age, as well as interactions among these three variables, were found to affect some static histomorphometric indexes in healthy Brazilian subjects.     

How Does Bone Quality Differ Between Healthy-weight and Overweight Adolescents and Young Adults?

Background

Overweight youth have greater bone mass than their healthy-weight peers but sustain more fractures. However, it is unclear whether and how excess body fat influences bone quality in youth.

Questions/purposes

We determined whether overweight status correlated with three-dimensional aspects of bone quality influencing bone strength in adolescent and young adult females and males.

Methods

We categorized males (n = 103; mean age, 17 years) and females (n = 85; mean age, 18 years) into healthy-weight and overweight groups. We measured lean mass (LM) and fat mass (FM) with dual-energy x-ray absorptiometry (DXA). We used high-resolution peripheral quantitative CT to assess the distal radius (7% site) and distal tibia (8% site). Bone quality measures included total bone mineral density (Tt.BMD), total area (Tt.Ar), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), separation (Tb.Sp), and thickness (Tb.Th). We used multiple regression to compare bone quality between healthy-weight and overweight adolescents adjusting for age, ethnicity, limb length, LM, and FM.

Results

Overweight males had higher (10%–21%) Tt.BMD, BV/TV, and Tb.N and lower Tb.Sp at the tibia and lower Tt.Ar at the radius than healthy-weight males. No differences were observed between overweight and healthy-weight females. LM attenuated the differences in bone quality between groups in males while FM negatively predicted Tt.BMD, BV/TV, Tb.N, and Tb.Th.

Conclusions

Our data suggest overweight males have enhanced bone quality compared with healthy-weight males; however, when group differences are interpreted in the context of the mechanostat theory, it appears bone quality of overweight adolescents adapts to LM and not to greater FM.     

Does Physical Activity in Adolescence Have Site‐Specific and Sex‐Specific Benefits on Young Adult Bone Size,Content, and Estimated Strength?

The long‐term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSI_p) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSI_c) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z‐scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSI_p, p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSI_p in males, and greater CoA, CoC, and TrC in females. © 2014 American Society for Bone and Mineral Research.     

通过Micro-CT评价瘦素受体缺乏的2型糖尿病小鼠四肢骨的骨代谢变化

目的探讨瘦素受体(leptin receptor,Lepr)缺乏的2型糖尿病小鼠的骨骼表型,为2型糖尿病((T2DM)合并骨质疏松(OP)的防治提供一个新的靶点。方法获取20只14周龄雄性db/db小鼠(瘦素受体缺乏小鼠)和野生型小鼠(C57BL小鼠)的胫骨(各10只),通过Micro-CT检测比较两者骨小梁相对体积(BV/TV)、骨表面积组织体积比值(BS/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、骨结构模型指数(SMI)、骨皮质厚度(Ct.Th)、骨皮质面积(Ct.Ar)等骨微结构参数的差异。结果与野生型小鼠相比,14周龄的db/db小鼠的胫骨骨小梁相对体积(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)明显减小,小梁骨间距(Tb.Sp)相应增加,皮质骨厚度(Ct.Th)、横截面积(Ct.Ar)减小,两者比较差异均有显著统计学意义(P0.05);其结构模式指数(structure model index,SMI)较野生型明显减小,两者比较差异均有统计学意义(P0.05)。结论 2型糖尿病可能是通过瘦素受体参与的信号通路影响了骨量变化,为利用该模型进行DOP病因及治疗方法研究提供了新的方向。且在缺乏瘦素信号传导的情况下,骨质量和强度的降低验证了瘦素在体内起着合成代谢骨因子的作用。     

Three-dimensional microstructure of the bone in a hamster model of senile osteoporosis

Age-related bone loss, which is poorly characterized, is a major underlying cause of osteoporotic fractures in the elderly. In order to identify the morphological feature of age-related bone loss, we investigated sex and site (tibia, femur and vertebra) dependence of bone microstructure in aging hamsters from 3 to 24 months of age using micro-CT. In the proximal tibia and distal femur, trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and bone mineral density (BMD) increased to a maximum at 6 or 12 months and then declined progressively from 12 to 24 months of age. Trabecular separation (Tb.Sp), trabecular bone pattern factor (TBPf) and structure model index (SMI) increased with age. As compared with male hamsters, BV/TV and Tb.N were significantly lower in females at 18 and 24 months of age. Age-related decrease of trabecular BV/TV in the vertebral body was less than that of the femoral and tibial metaphyses. In the mid-femoral diaphysis, cortical bone area remained constant from 3 to 24 months of age. Cortical thickness decreased from 12 to 24 months and cortical BMD declined significantly from 18 to 24 months of age. These findings indicate that skeletal site and sex differences exist in hamster bone structure. Age-related bone changes in hamsters resemble those in humans. We conclude that hamster may be a useful model to study at least some aspects of bone loss during human aging.     

Quantitative and Qualitative Changes of Bone in Psoriasis and Psoriatic Arthritis Patients

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by periarticular bone loss and new bone formation. Current data regarding systemic bone loss and bone mineral density (BMD) in PsA are conflicting. The aim of this study was to evaluate bone microstructure and volumetric BMD (vBMD) in patients with PsA and psoriasis. We performed HR‐pQCT scans at the ultradistal and periarticular radius in 50 PsA patients, 30 psoriasis patients, and 70 healthy, age‐ and sex‐related controls assessing trabecular bone volume (BV/TV), trabecular number (Tb.N), inhomogeneity of the trabecular network, cortical thickness (Ct.Th), and cortical porosity (Ct.Po), as well as vBMD. Trabecular BMD (Tb.BMD, p = 0.021, 12.0%), BV/TV (p = 0.020, –11.9%), and Tb.N (p = 0.035, 7.1%) were significantly decreased at the ultradistal radius and the periarticular radius in PsA patients compared to controls. In contrast, bone architecture of the ultradistal radius and periarticular radius was similar in patients with psoriasis and healthy controls. Duration of skin disease was associated with low BV/TV and Tb.N in patients with PsA. These data suggest that trabecular BMD and bone microstructure are decreased in PsA patients. The observation that duration of skin disease determines bone loss in PsA supports the concept of subclinical musculoskeletal disease in psoriasis patients. © 2015 American Society for Bone and Mineral Research.     

Decreased Quantity and Quality of the Periarticular and Nonperiarticular Bone in Patients With Rheumatoid Arthritis: A Cross‐Sectional HR‐pQCT Study

Rheumatoid arthritis (RA) is a highly bone destructive disease. Although it is well established that RA leads to bone loss and increased fracture risk, current knowledge on the microstructural changes of bone in RA is still limited. The purpose of this study was to assess the microstructure of periarticular and nonperiarticular bone in female and male RA patients and compare it with respective healthy controls. We performed two high‐resolution peripheral quantitative computed tomography (HR‐pQCT; Xtreme‐CT) scans, one of the distal radius and one of the ultradistal radius in 90 patients with RA (60 females, 30 males) and 70 healthy controls (40 females, 30 males) matched for sex, age, and body mass index. Volumetric bone mineral density (vBMD), bone geometry, and bone microstructure including trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th) and cortical porosity (Ct.Po) were assessed. At the distal and ultradistal radius, trabecular (p = 0.005 and p < 0.001) and cortical BMD (p < 0.001 and p < 0.001) were significantly decreased in male and female patients with RA, respectively. BV/TV was also decreased at both sites, based on lower Tb.N in female RA (p < 0.001 for both sites) and lower Tb.Th (p = 0.034 and p = 0.005) in male RA patients compared with respective healthy controls. Cortical thinning (p = 0.018 and p = 0.002) but not Ct.Po (p = 0.070 and p = 0.275) was pronounced in male and female RA patients at the distal radius. Cortical perimeter was increased in male and female RA patients at both sites. Multiple regression models showed that bone geometry (cortical perimeter) is predominantly influenced by age of the RA patient, cortical thickness by both age and disease duration, and trabecular microstructure predominantly by the disease duration. In summary, these data show profound deterioration of bone microstructure in the appendicular skeleton of RA patients at both periarticular and nonperiarticular sites. © 2014 American Society for Bone and Mineral Research.     

Bone Structure and Volumetric BMD in Overweight Children: A Longitudinal Study

The effect of excess body fat on bone strength accrual is not well understood. Therefore, we assessed bone measures in healthy weight (HW) and overweight (OW) children. Children (9–11 yr) were classified as HW (n = 302) or OW (n = 143) based on body mass index. We assessed total (ToD) and cortical (CoD) volumetric BMD and bone area, estimates of bone strength (bone strength index [BSI]; stress‐strain index [SSIp]), and muscle cross‐sectional area (CSA) at the distal (8%), midshaft (50%), and proximal (66%) tibia by pQCT. We used analysis of covariance to compare bone outcomes at baseline and change over 16 mo. At baseline, all bone measures were significantly greater in OW compared with HW children (+4–15%; p ≤ 0.001), with the exception of CoD at the 50% and 66% sites. Over 16 mo, ToA increased more in the OW children, whereas there was no difference for change in BSI or ToD between groups at the distal tibia. At the tibial midshaft, SSIp was similar between groups at baseline when adjusted for muscle CSA, but low when adjusted for body fat in the OW group. At both sites, bone strength increased more in OW because of a greater increase in bone area. Changes in SSIp were associated with changes in lean mass (r = 0.70, p < 0.001) but not fat mass. In conclusion, although OW children seem to be at an advantage in terms of absolute bone strength, bone strength did not adapt to excess body fat. Rather, bone strength was adapted to the greater muscle area in OW children.     

Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine.

Cancellous bone morphometry was investigated in the sagittal plane of lumbar vertebrae using histoquantitation. The aim of this study was to identify variations in cancellous bone architecture at increasing states of intervertebral disc (IVD) disorganization after age adjustment and to investigate regional variations within the whole vertebral body. Measurements were taken of the ratio of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12-L5) of 19 men and 8 women were removed at autopsy from an adult sample with no clinical history of bone-related disease or histologically identifiable bone disease. It was found that degeneration of the IVD becomes more common with increasing age. After age-adjustment, significant increases in the proportion of BV/TV were observed in the presence of advancing IVD disorganization. Significant architectural changes were observed in the anterior regions of the vertebral body with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were found at posterior regions. Bone loss was observed in central regions (most distant from the cortex) as IVD disorganization increased through reduction in both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a response to a redistribution of load to the vertebral body periphery as a result of IVD disorganization. It appears that trabecular morphology is related to the condition of the associated IVD, rather than being the sole consequence of a loss of BV/TV with age. This relationship could influence the occurrence of vertebral body crush fracture.     

Gender differences in trabecular bone architecture of the distal radius assessed with magnetic resonance imaging and implications for mechanical competence

High-resolution magnetic resonance imaging (hrMRI) has recently made it possible to evaluate trabecular bone structure in vivo. Despite obvious gender differences in fracture incidence at the distal radius, little is known about gender differences in trabecular bone microarchitecture and its relationship to the structural strength of the forearm. The aim of this study was to determine trabecular bone structure in the distal radius of elderly women and men and its correlation with failure loads of the distal radius as determined in a fall configuration. Specifically, we tested the hypotheses that structural indices differ between women and men and that they offer information that is independent from BMD for predicting structural strength. Intact right arms were obtained from 73 formalin-fixed cadavers (age 80±11 years, 43 women, 30 men). Trabecular structural indices (apparent bone volume fraction [app. BV/TV], trabecular number [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app. Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis, using hrMRI with 156 µm in-plane resolution and proprietary digital image analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women displayed significantly lower BMD (–29.8%, p <0.001), app. BV/TV (–8.2%, p <0.05) and app. Tb.Th (–10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and fractal dimension did not differ significantly. Structural parameters differed between normal and osteopenic women (BV/TV: –11%, p <0.01; Tb.Th: –8%, p <0.001) and between normal and osteoporotic women BV/TV: –21%, p <0.001; Tb.Th: –16%, p <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information independent from BMD in the prediction of radial failure loads in multiple regression models. These findings imply that it should be of clinical interest to monitor both bone mass and trabecular microstructure for predicting osteoporotic fracture risk.