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The effect of age on the microarchitecture and profile of gene expression in femoral head and neck bone from patients with osteoarthritis.

ABSTRACT: Ageing of the skeleton is characterised by decreased bone mineral density, reduced strength, and increased risk of fracture. Although it is known that these changes are determined by the activities of bone cells through the processes of bone modelling and remodelling, details of the molecular mechanisms that underlie age-related changes in bone are still missing. Here, we analysed age-related changes in bone microarchitecture along with global gene expression in samples obtained from patients with osteoarthritis (OA). We hypothesised that changes would be evident in both microarchitecture and gene expression and aimed to identify novel molecular mechanisms that underlie ageing processes in bone. Samples of femoral head and neck were obtained from patients undergoing hip arthroplasty for OA, who were either ≤60 years or ≥70 years of age. Bone microarchitecture was analysed in cores of trabecular bone from the femoral head (17 from the younger group and 18 from the older), and cortical bone from the femoral neck (25 younger/22 older), using a Skyscan 1172 microCT scanner (Bruker). Gene expression was compared between the two age groups in 20 trabecular samples from each group, and 10 cortical samples from each group, using Clariom S Human microarrays (ThermoFisher Scientific). We found no significant changes between the two age groups in indices of trabecular or cortical bone microarchitecture. Gene expression analysis identified seven genes that had higher expression in the older group, including the transcription factor EGR1 and the glucose transporter SLC2A3 (GLUT3), and 21 differentially expressed genes in cortical bone samples (P<0.05, fold change>2). However, none of the comparisons of gene expression had false discovery rate-adjusted P<0.1. In contrast to our working hypothesis, we found only minor differences in gene expression and no differences in bone microarchitecture between the two age-groups. It is possible that pathological processes related to OA provide protection against age-related changes in bone. Our study suggests that in patients with OA, the bone properties measured here in femoral head and neck do not deteriorate significantly from the sixth to the eighth decade of life.

SUBMITTER: Naot D

PROVIDER: S-EPMC7292911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundGlucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH.PurposesTo investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH.MethodsFrom September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels.ResultsIn the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH.ConclusionsGONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.

Project description:Osteoarthritis (OA) is known to involve profound changes in bone density and microstructure near to, and even distal to, the joint. Critically, however, a full, spatial picture of these abnormalities has not been well documented in a quantitative fashion in hip OA. Here, micro-computed tomography (44.8 μm/voxel) and data-driven computational anatomy were used to generate 3-D maps of the distribution of bone density and microstructure in human femoral neck samples with early (6F/4M, mean age = 51.3 years), moderate (14F/8M, mean age = 60 years), and severe (16F/6M, mean age = 63.3 years) radiographic OA. With increasing severity of radiographic OA, there was decreased cortical bone mineral density (BMD) (p=0.003), increased cortical thickness (p=0.001), increased cortical porosity (p=0.0028), and increased cortical cross-sectional area (p=0.0012, due to an increase in periosteal radius (p=0.018)), with no differences detected in the total femoral neck or trabecular compartment measures. No OA-related region-specific differences were detected through Statistical Parametric Mapping, but there were trends towards decreased tissue mineral density (TMD) in the inferior femoral neck with increasing OA severity (0.050 < p ≤ 0.091), possibly due to osteophytes. Overall, the lack of differences in cortical TMD among radiographic OA groups indicated that the decrease in cortical BMD with increasing OA severity was largely due to the increased cortical porosity rather than decreased tissue mineralization. As porosity is inversely associated with stiffness and strength in cortical bone, increased porosity may offset the effect that increased cortical cross-sectional area would be expected to have on reducing stresses within the femoral neck. The use of high-resolution imaging and quantitative spatial assessment in this study provide insight into the heterogeneous and multi-faceted changes in density and microstructure in hip OA, which have implications for OA progression and fracture risk.

Project description:Teriparatide (TPTD) reduces risk of both vertebral and nonvertebral fracture, but increases bone mineral density (BMD) much more at the spine than the hip. TPTD and mechanical loading may have a synergistic anabolic effect on BMD, which may help explain these site-specific differences. Under normal daily activity, the femoral neck (FN) is under bending, placing one side under tension and the other under compression. We sought to further understand the relationship between mechanical loading and TPTD at the hip by investigating the effect of tensile versus compressive loading on TPTD stimulated bone formation indices in the human FN. Thirty-eight patients receiving total hip replacements for osteoarthritis were randomized to receive placebo (PBO) or TPTD for a mean treatment duration of 6 weeks prior to surgery, and double tetracycline labeling was administered to allow assessment of bone formation. The FN was harvested during surgery and analyzed for dynamic bone formation indices in the compressive and tensile regions of the endocortical and periosteal envelopes. Regression models relating outcome measures to patient characteristics including sex, age, body weight, and FN geometry were also analyzed. Overall, bone formation was higher with TPTD versus placebo on the endocortical surface, but not the periosteal surface. The level of bone formation in both TPTD and placebo groups was greater on the tensile endocortical surface and the compressive periosteal surface. There was a trend toward decreased endocortical eroded surface with TPTD in the compressive but not the tensile region. Patient age and sex explained the greatest variability in endocortical bone formation, and patient body mass and sex explained the greatest variability in periosteal bone formation. Our data represent the first dynamic comparison of teriparatide treatment under two loading modalities in human FN samples. Future work could determine whether specific hip loading intervention could amplify the benefits of teriparatide on the hip in clinical settings.

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The effect of age on the microarchitecture and profile of gene expression in femoral head and neck bone from patients with osteoarthritis.

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