Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study.

We assessed the role of low aBMD and impaired architecture-assessed by an HR-pQCT system-in a case-control study of postmenopausal women with fractures. Vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone, independent of aBMD assessed by DXA. INTRODUCTION: Alterations of bone architecture and low BMD both contribute to skeletal fragility, but the contribution of cortical and trabecular architecture, independently of areal BMD (aBMD), to the risk of fracture in postmenopausal women has not been thoroughly evaluated. We assessed the role of impaired architecture and low BMD in postmenopausal women with fractures. MATERIALS AND METHODS: A matched case-control study in women from the OFELY cohort was performed after 13 years of follow-up. One hundred one women (mean, 73.7+/-8 years) who sustained a fragility fracture during the follow-up of the study were age-matched with one control who never had a fracture. Density and architecture at the distal radius and tibia were measured with high-resolution pQCT (HR-pQCT) using an XTreme CT (Scanco Medical AG, Bassersdorf, Switzerland). aBMD at the total hip and ultradistal radius was measured by DXA. RESULTS: There were 80 peripheral fractures in 72 women, 44 vertebral fractures in 34 women, and both types of fractures in 5 women over the 14 years of follow-up. At the distal radius, women with fractures had lower volumetric total (D tot) and trabecular (D trab) BMDs, BV/TV, cortical thickness (Cort Th), trabecular number (TbN), and trabecular thickness (TbTh) and higher trabecular separation (TbSp) and distribution of trabecular separation (TbSpSd) than controls without fractures. In a logistic model, each SD decrease of volumetric total and trabecular densities was associated with a significantly increased risk of fracture at both sites (ORs ranged from 2.00 to 2.47). After adjusting for aBMD measured by DXA at the ultradistal radius, differences between cases and controls remained significant for D trab, and there was a similar trend for TbN, TbSp, and TbSpSd, with adjusted ORs ranging from 1.32 to 1.50. At the distal tibia, before and after adjusting for total hip aBMD, differences between cases and controls remained significant for D tot, D trab, Cort Th, and TbTh, with adjusted ORs ranging from 1.80 to 2.09. CONCLUSIONS: In postmenopausal women, vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone that can be assessed noninvasively and that are partially independent of aBMD assessed by DXA.     

Postpubertal Architectural Developmental Patterns Differ Between the L3 Vertebra and Proximal Tibia in Three Inbred Strains of Mice

An understanding of normal microarchitectural bone development patterns of common murine models is needed. Longitudinal, structural, and mineralization trends were evaluated by in vivo μCT over 12 time points from 6–48 wk of age at the vertebra and tibia of C3H/HeN, C57BL/6, and BALB/C mice. Longitudinal growth occurred rapidly until 8–10 wk, slowed as the growth plate bridged, and fused at 8–10 mo. Structural augmentation occurred through formation of trabeculae at the growth plate and thickening of existing ones. In the vertebrae, BV/TV increased rapidly until 12 wk in all strains. Between 12 and 32 wk, the architecture was stable with BV/TV deviating <1.1%, 1.6%, and 3.4% for the C57BL/6, BALB/C, and C3H/HeN mice. In contrast, the tibial architecture changed continuously but more moderately for BV/TV and TbTh compared with the vertebra and with comparable or larger changes for TbN and TbSp. Age‐related trabecular deterioration (decreased BV/TV and TbN; increased TbSp and structure model index) was evident at both sites at 32 wk. In all strains, the cortex continued to develop after trabecular values peaked. The temporal plateau of BMD was variable across mouse strains and site, whereas tissue mineral density was attained at ～6 mo for all sites and strains. Geometric changes at the tibial diaphysis occurred rapidly until 8–10 wk, providing the C57BL/6 mice and C3H/HeN mice with the highest torsional and compressive rigidity, respectively. In summary, key skeletal development milestones were identified, and architectural topology at the vertebra was found to be more stable than at the tibia.     

Skeletal muscle mass is associated with bone geometry and microstructure and serum insulin-like growth factor binding protein-2 levels in adult women and men

Skeletal muscle and bone form highly‐integrated systems that undergo significant age‐related changes, but the relationships between muscle mass and trabecular versus cortical bone or trabecular microarchitecture have not been systematically investigated. Thus, we examined the association between appendicular skeletal muscle mass (ASM) relative to height squared (relative ASM) and bone parameters at several sites assessed by conventional as well as high‐resolution peripheral QCT in a cohort of 272 women and 317 men aged 20 to 97 years. In women, relative ASM was associated with cortical thickness (CtTh) at the femoral neck, lumbar spine, radius, and tibia (age‐and physical activity adjusted r = 0.19–0.32; all p < 0.01). Relative ASM was also associated with trabecular volumetric bone mineral density (vBMD) at the femoral neck and spine (all p < 0.05), and trabecular bone volume to tissue volume (BV/TV), number (TbN), thickness (TbTh), and separation (TbSp) at the radius (all p ≤ 0.05). In all men, relative ASM was associated with CtTh at all sites (age‐ and physical activity–adjusted r = 0.17–0.28; all p < 0.01). Associations between relative ASM and trabecular vBMD at the spine in men were lost after adjusting for age; however, relative ASM was associated with trabecular vBMD at the femoral neck and TbN and TbSp at the radius (all p < 0.01). We also investigated circulating factors associated with bone health that may be indicative of relative ASM and found that serum insulin‐like growth factor (IGF) binding protein‐2 (IGFBP‐2) levels were the most robust negative predictors of relative ASM in both sexes. Collectively, these data add to the growing body of evidence supporting the highly‐integrated nature of skeletal muscle and bone, and provide new insights into potential biomarkers that reflect the health of the musculoskeletal system. © 2012 American Society for Bone and Mineral Research.     

Regional variations of vertebral trabecular bone microstructure with age and gender

The vertebral trabecular bone has a complex three-dimensional (3D) microstructure, with inhomogeneous morphology. A thorough understanding of regional variations in the microstructural properties is crucial for evaluating age- and gender-related bone loss of the vertebra, and may help us to gain more insight into the mechanism of the occurrence of vertebral osteoporosis and the related fracture risks. INTRODUCTION: The aim of this study was to identify regional differences in 3D microstructure of vertebral trabecular bone with age and gender, using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM). METHODS: We used 56 fourth lumbar vertebral bodies from 28 women and men (57-98 years of age) cadaver donors. The subjects were chosen to give an even age and gender distribution. Both women and men were divided into three age groups, 62-, 77- and 92-year-old groups. Five cubic specimens were prepared from anterosuperior, anteroinferior, central, posterosuperior and posteroinferior regions at sagittal section. Bone specimens were examined by using micro-CT and SEM. RESULTS: Reduced bone volume (BV/TV), trabecular number (Tb.N) and connectivity density (Conn.D), and increased structure model index (SMI) were found between ages 62 and 77 years, and between ages 77 and 92 years. As compared with women, men had higher Tb.N in the 77-year-old group and higher Conn.D in the 62- and 77-year-old groups. The central and anterosuperior regions had lower BV/TV and Conn.D than their corresponding posteroinferior region. Increased resorbing surfaces, perforated or disconnected trabeculae and microcallus formations were found with age. CONCLUSION: Vertebral trabeculae are microstructurally heterogeneous. Decreases in BV/TV and Conn.D with age are similar in women and men. Significant differences between women and men are observed at some microstructural parameters. Age-related vertebral trabecular bone loss may be caused by increased activity of resorption. These findings illustrate potential mechanisms underlying vertebral fractures.     

In Vivo Assessment of Architecture and Micro-Finite Element Analysis Derived Indices of Mechanical Properties of Trabecular Bone in the Radius

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (μFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n= 22, mean age 58 ± 7 years) and (II) postmenopausal women with spine or femur BMD −1 SD to −2.5 SD below young normal (n= 37, mean age 62 ± 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young’s moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with μFE modeling in vivo in the study of osteoporosis. Received: 13 December 2000 / Accepted: 30 May 2001     

Individual trabeculae segmentation (ITS)–based morphological analysis of high‐resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis

Idiopathic osteoporosis (IOP) in premenopausal women is a poorly understood entity in which otherwise healthy women have low‐trauma fracture or very low bone mineral density (BMD). In this study, we applied individual trabeculae segmentation (ITS)–based morphological analysis to high‐resolution peripheral quantitative computed tomography (HR‐pQCT) images of the distal radius and distal tibia to gain greater insight into skeletal microarchitecture in premenopausal women with IOP. HR‐pQCT scans were performed for 26 normal control individuals and 31 women with IOP. A cubic subvolume was extracted from the trabecular bone compartment and subjected to ITS‐based analysis. Three Young's moduli and three shear moduli were calculated by micro–finite element (µFE) analysis. ITS‐based morphological analysis of HR‐pQCT images detected significantly decreased trabecular plate and rod bone volume fraction and number, decreased axial bone volume fraction in the longitudinal axis, increased rod length, and decreased rod‐to‐rod, plate‐to‐rod, and plate‐to‐plate junction densities at the distal radius and distal tibia in women with IOP. However, trabecular plate and rod thickness did not differ. A more rod‐like trabecular microstructure was found in the distal radius, but not in the distal tibia. Most ITS measurements contributed significantly to the elastic moduli of trabecular bone independent of bone volume fraction (BV/TV). At a fixed BV/TV, plate‐like trabeculae contributed positively to the mechanical properties of trabecular bone. The results suggest that ITS‐based morphological analysis of HR‐pQCT images is a sensitive and promising clinical tool for the investigation of trabecular bone microstructure in human studies of osteoporosis. © 2010 American Society for Bone and Mineral Research     

Subchondral bone micro-architectural alterations in osteoarthritis: a synchrotron micro-computed tomography study

OBJECTIVES: We evaluated the three-dimensional (3D) micro-architecture of subchondral trabecular (Tb) bone in osteoarthritis (OA). Due to high signal-to-noise ratio and high resolution, micro-computed tomography (micro-CT) by synchrotron radiation is considered as the gold standard for bone micro-architecture imaging. DESIGN: Subchondral bone were extracted from femoral heads in OA cases in areas without cartilage (OAc-; n=6) and in adjacent areas with cartilage (OAc+; n=6) and compared to eight subchondral bone cores from osteoporosis cases (OP). The voxel size of images was 10.13 microm. We measured the bone volume fraction (BV/TV) and morphological parameters: Tb thickness (TbTh), Tb spacing (TbSp), Tb number (TbN), and bone surface/bone volume (BS/BV). The degree of anisotropy (DA), the connectivity by the Euler number and the degree of mineralization (DM) were equally assessed. RESULTS: BV/TV and morphological parameters showed significant differences between OAc- and OP samples (P<0.01 except TbTh: P<0.05) and between OAc- and OAc+ (0.05相似文献   

X‐ray–verified fractures are associated with finite element analysis–derived bone strength and trabecular microstructure in young adult men

It has been suggested that fracture during childhood could be a predictor of low peak bone mass and thereby a potential risk factor for osteoporosis and fragility fractures later in life. The aim of this cross‐sectional, population‐based study was to investigate whether prevalent fractures, occurring from birth to young adulthood, were related to high‐resolution peripheral quantitative computed tomography (HR‐pQCT)–derived trabecular and cortical microstructure, as well as bone strength estimated by finite element (FEA) analysis of the radius and tibia in 833 young adult men around the time of peak bone mass (ages 23 to 25 years). In total, 292 subjects with prevalent X‐ray–verified fractures were found. Men with prevalent fractures had lower trabecular bone volume fraction (BV/TV) at the radius (5.5%, p < 0.001) and tibia (3.7%, p < 0.001), as well as lower cortical thickness (5.1%, p < 0.01) and cortical cross‐sectional area (4.1%, p < 0.01) at the tibia. No significant differences were seen for the cortical porosity or mean pore diameter. Using a logistic regression model (including age, smoking, physical activity, calcium intake, height, and weight as covariates), every SD decrease of FEA‐estimated failure load was associated with an increased prevalence of fractures at both the radius (odds ratio [OR] 1.22 [1.03–1.45]) and tibia (OR 1.32 [1.11–1.56]). Including dual‐energy X‐ray absorptiometry (DXA)–derived radius areal bone mineral density (aBMD), cortical thickness, and trabecular BV/TV simultaneously in a logistic regression model (with age, smoking, physical activity, calcium intake, height, and weight as covariates), BV/TV was inversely and independently associated with prevalent fractures (OR 1.28 [1.04–1.59]), whereas aBMD and cortical thickness were not (OR 1.19 [0.92–1.55] and OR 0.91 [0.73–1.12], respectively). In conclusion, prevalent fractures in young adult men were associated with impaired trabecular BV/TV at the radius, independently of aBMD and cortical thickness, indicating that primarily trabecular bone deficits are of greatest importance for prevalent fracture in this population. © 2013 American Society for Bone and Mineral Research.     

Intermittent Fugu parathyroid hormone 1 (1-34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats

Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1-34) sharing only 53% identity with hPTH(1-34). Here we demonstrate the in vivo actions of fPth1(1-34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 microg-1,000 microg/kg body weight (b.w.), (30fPth1-1,000fPth1)] or hPTH [30 microg-100 microg/kg b.w. (30hPTH-100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 microg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1-34), we have clearly established the efficacy of fPth1 (1-34) as an anabolic bone agent.     

Sex differences of human trabecular bone microstructure in aging are site-dependent.

In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.     

Quantification of regional variations in glenoid trabecular bone architecture and mineralization using clinical computed tomography images

The purpose of this study was to demonstrate feasibility of a clinical CT imaging and analysis technique to quantify regional variations in trabecular bone architecture and mineralization of glenoid bones. Specifically, our objective was to determine to what extent clinical CT imaging of intact upper extremities can describe variations of trabecular bone architectures at anatomic and peri‐implant regions by comparing trabecular bone architectures as measured by high‐resolution, micro CT imaging of same excised glenoid bones. Bone volume fraction (BVF), trabecular bone thickness (TbTh), number of trabecular bone (TbN), spacing (TbS), pattern factor (TbPf), bone surface area (BSA), and skeletal connectivity (Conn.), in addition to bone mineral content (BMC) and bone mineral density (BMD), were quantified from both clinical and micro CT images using whole bone, anatomic, and peri‐implant bone masks. Strong correlations of BVF, TbTh, TbSp, BMC, and BMD were found between clinical CT and micro CT imaging methods. The variations in BVF, TbTh, TbSp, TbN, BMC, and BMD at anatomical and peri‐implant regions were larger than those at whole bone regions. In this study, we have demonstrated that this clinical CT imaging methodology can be used to quantify variations of a patient's glenoid bone at anatomic and peri‐implant levels. Statement of Clinical Significance. An in vivo quantitative assessment of glenoid trabecular bone architecture in the anatomic and peri‐implant regions may improve our understanding on the role of bone quality on glenoid component loosening following total shoulder arthroplasty. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:85–96, 2018.     

Differences in Macro‐ and Microarchitecture of the Appendicular Skeleton in Young Chinese and White Women

To identify the racial differences in macro‐ and microstructure of the distal radius and tibia that may account for the lower fracture rates in Asians than whites, we studied 61 healthy premenopausal Chinese and 111 white women 18–45 yr of age using high‐resolution pQCT (HR‐pQCT). The Chinese were shorter and leaner. Distal radius total cross‐sectional area (CSA) was 14.3% smaller in Chinese because of an 18.0% smaller trabecular area (p < 0.001). Cortical thickness was 8.8% greater in the Chinese, but cortical area was no different. Total volumetric BMD (vBMD) was 10.3% higher in the Chinese because of the 8.8% higher cortical thickness and 2.8% greater cortical density (all p < 0.01). Trabecular vBMD and bone volume/tissue volume (BV/TV) did not differ by race because trabeculae were 7.0% fewer but 10.8% thicker in Chinese than whites (both p < 0.01). Similar results were found at the distal tibia. Lower fracture risk in Chinese women may be partly caused by thicker cortices and trabeculae in a smaller bone‐more bone within the bone than in whites.     

Bone microstructure at the distal tibia provides a strength advantage to males in late puberty: An HR‐pQCT study

Bone is a complex structure with many levels of organization. Advanced imaging tools such as high‐resolution (HR) peripheral quantitative computed tomography (pQCT) provide the opportunity to investigate how components of bone microstructure differ between the sexes and across developmental periods. The aim of this study was to quantify the age‐ and sex‐related differences in bone microstructure and bone strength in adolescent males and females. We used HR‐pQCT (XtremeCT, Scanco Medical, Geneva, Switzerland) to assess total bone area (ToA), total bone density (ToD), trabecular bone density (TrD), cortical bone density (CoD), cortical thickness (Cort.Th), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular spacing standard deviation (Tb.Sp SD), and bone strength index (BSI, mg²/mm⁴) at the distal tibia in 133 females and 146 males (15 to 20 years of age). We used a general linear model to determine differences by age‐ and sex‐group and age × sex interactions (p < 0.05). Across age categories, ToD, CoD, Cort.Th, and BSI were significantly lower at 15 and 16 years compared with 17 to 18 and 19 to 20 years in males and females. There were no differences in ToA, TrD, and BV/TV across age for either sex. Between sexes, males had significantly greater ToA, TrD, Cort.Th, BV/TV, Tb.N, and BSI compared with females; CoD and Tb.Sp SD were significantly greater for females in every age category. Males' larger and denser bones confer a bone‐strength advantage from a young age compared with females. These structural differences could represent bones that are less able to withstand loads in compression in females. © 2010 American Society for Bone and Mineral Research     

Analysis of Trabecular Microstructure and Vascular Distribution of Capital Femoral Epiphysis Relevant to Legg–Calve–Perthes Disease

Legg–Calve–Perthes disease is characterized by the capital femoral epiphyseal collapse, which occurs more reliably in the anterior quadrant than the more weight‐bearing lateral quadrant. The purpose of this study was to determine whether there is a vascular or microstructural predisposition for anterior femoral epiphyseal collapse in Perthes disease. Thirty‐two cadaveric proximal femoral epiphyses from 17 subjects (age 4–14 years old) underwent micro‐computed tomography at 10‐μm resolution. Each quadrant was analyzed for four markers of trabecular architecture: bone volume fraction (BV/TV), trabecular thickness, trabecular separation (TbSp), and trabecular number (TbN). Vascular channels were then mapped in each quadrant, identified by correlating surface topography with cross‐sectional imaging. One‐way analysis of variance revealed an overall difference between quadrants (p < 0.001) in BV/TV, TbN, and TbSp. However, post hoc analysis revealed there was no significant difference between the anterior and lateral quadrants for any of the four markers of trabecular architecture. Vascular channel mapping illustrated a predominance of vessels in the posterior half of the epiphysis compared to the anterior half (8.7 ± 4.0 vs. 3.4 ± 3.1 vascular channels, p < 0.001). The lack of microstructural differences between the anterior and lateral quadrants, and the predominance of vascular channels in the posterior half of the epiphysis with posteriorly‐based medial femoral circumflex and ligamentum teres vessels suggests that the anterior femoral epiphysis may be a relative vascular watershed region, which predisposes it to collapse after the vascular insult of Perthes disease. Clinical significance: Improved understanding of the pathophysiology of anterior femoral epiphyseal collapse may inform future treatments aimed at revascularization. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1784–1789, 2019     

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

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

A study of trabecular bones in ovariectomized goats with micro-computed tomography and peripheral quantitative computed tomography

Osteoporotic fractures occur most frequently in trabeculae-rich skeletal sites. The purpose of this study was to use a high-resolution micro-computed tomography (micro-CT) to investigate the changes in trabecular bone microarchitecture and to use a peripheral quantitative computed tomography (pQCT) to study changes in volumetric bone mineral density (BMD) in a large animal model resulted from ovariectomy (OVX). Ten adult goats were used for this study. The first iliac crest biopsy was harvested before OVX and served as baseline; the second biopsy was collected 6 months later from the opposite side for both pQCT and micro-CT measurements. Results showed that after 6 months of OVX, the BMD of the iliac crest biopsies decreased significantly by 16.3% (P < 0.05). The bone volume density (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D) measured with micro-CT decrease significantly after OVX, with an average decrease of 8.34%, 8.51%, and 18.52% (P < 0.05 each), respectively. The trabecular plate separation (Tb.Sp) was 8.26% (P < 0.05) greater than baseline after OVX. Significant correlations were found between the reduction of BMD and the decreases of BV/TV and Tb.N (r = 0.839 and 0.719, respectively; P< 0.001 both), as well as the increase of Tb.Sp (r = -0.758, P< 0.001) and SMI (r = -0.697, P< 0.001). In conclusion, this was the first experimental study in goat model to show that OVX-induced bone loss in goats was attributed by deterioration of trabecular microarchitecture.     

Effect of implanted bisphosphonate-enriched cement on the trabecular microarchitecture of bone in a rat model using micro-computed tomography

Purpose

Bisphosphonates (BPs) are antiresorptive drugs typically used to inhibit bone resorption. The latest reports show that BPs play an important role in not only achieving better bone mineral density but also in improving bone microarchitecture. The mechanism of action of the BPs is complex and multifactorial. We tried to determine whether there are any changes in the microarchitectural bone structure during local use of BP (Pamifos 60). The aim of this study was to see if BP-enriched cement used in rat models had positive effects on bone formation.

Methods

Research was performed on 40 adult male Wistar rats that were divided into four groups: two control groups and two experimental groups. Rats in the experimental groups were implanted with BP-enriched cement into the bone, while the control group rats were implanted with clean bone cement (without BP). Micro-computed tomography was applied for the investigation of trabecular microarchitecture of the proximal physis of the tibial bone in all animals three and six weeks after surgery. In all microCT images variables such as bone volume density (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp) and trabecular number (TbN) were used to describe trabecular bone morphometry.

Results

The major finding of this study is that using BP-enriched cement results in distinct changes in bone microarchitecture. We showed that local use of pamidronate (Pamifos 60) in orthopaedic cement had a positive effect on bone formation. It significantly changed three variables. We noticed increasing bone volume fraction and trabecular thickness together with decreasing trabecular separation.

Conclusion

In this paper we demonstrate the efficacy of using BP-enriched cement in vitro in the tibiae of rats. Our most significant finding based on micro-CT picture analysis allows us to start further work on more suitable applications of BP-enriched cement in humans. We believe that future successful experiments will facilitate potential use of BP-enriched cement in clinical applications.     

Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway

Previously, dietary supplementation with dried plums, a rich source of polyphenolic compounds with antioxidant and anti-inflammatory properties, has been shown to improve bone density, microstructure and biomechanics in female animal models of osteopenia. We designed this study to determine the extent to which dried plum prevents skeletal deterioration in gonadal hormone deficient male animals and to begin to understand its mechanism of action. Sixty 6-month-old male Sprague–Dawley rats were either sham-operated (Sham = 1 group) or orchidectomized (ORX = 4 groups) and randomly assigned to dietary treatments: standard semi-purified diet (Control) with either LD = 5%, MD = 15%, or HD = 25% (w/w) dried plum for 90 days. At the end of the treatment period, both the MD and HD dried plum completely prevented the ORX-induced decrease in whole body, femur, and lumbar vertebra bone mineral density (BMD). Biomechanical testing indicated that the MD and HD of dried plum prevented the ORX-induced decrease in ultimate load of the cortical bone as well as the compressive force and stiffness of trabecular bone within the vertebrae. Analyses of trabecular microarchitecture of the distal femur metaphysis and vertebral body revealed that HD dried plum protected against the decrease in trabecular bone volume (BV/TV) induced by ORX. In the distal femur, all doses of dried plum improved trabecular number (TbN) and separation (TbSp) compared to the ORX-control group, while MD and HD dried plum prevented the ORX-induced changes in vertebral TbN and TbSp. At the end of the 90-day treatment, no remarkable changes in serum osteocalcin or alkaline phosphatase in any of the treatment groups were observed, while serum insulin-like growth factor (IGF)-I was increased by dried plum. The ORX-induced increase in urinary deoxypyridinoline (DPD) excretion was completely prevented by all doses of dried plum coinciding with down-regulation of gene expression for receptor activator of NFκ-B ligand (RANKL) and osteoprotegerin (OPG) in the bone. We conclude that dried plum prevents osteopenia in androgen deficient male rats, and these beneficial effects may be attributed in part to a decrease in osteoclastogenesis via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.     

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.