Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices.

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function.Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands' second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected.Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed.Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

Differences in subchondral bone plate and cartilage thickness between women with anterior cruciate ligament reconstructions and uninjured controls.

OBJECTIVE: Anterior cruciate ligament (ACL) tears increase early onset osteoarthritis (OA) risk leading to cartilage and bone degradation. While the contribution of bone in OA development is unclear, evidence suggests that bone changes accompany cartilage degradation. This study aims to assess if regions with differences in subchondral bone plate thickness have differences in cartilage thickness when comparing ACL reconstructed (ACLR) knees of women ≥5 years post-injury to contralateral and controls with uninjured knees. DESIGN: Magnetic resonance imaging (MRI) assessed cartilage and high resolution peripheral quantitative computed tomography (HR-pQCT) assessed subchondral bone in both knees. Multimodal 3D image registration aligned anatomy. Maps of the spatial distribution of thickness on the articular surfaces were generated to compare women with ACL reconstructions to contralateral and controls with uninjured knees. RESULTS: ACLR knees had a thicker subchondral bone plate in the posterior and central lateral femur compared to contralateral knees (10.4% and 4.2% thicker, P = 0.032 and 0.032, W = 108 and 107, respectively) and in the posterior lateral femur compared to control knees (17.1% thicker, P = 0.014, W = 177). Cartilage differences were not detected (P > 0.05) in these regions. CONCLUSIONS: This study demonstrates that subchondral bone plate thickness differences are prominent following knee injury, as measured by HR-pQCT, but no statistically significant differences in cartilage morphology, measured by MRI, were found between ACLR knees compared to contralateral and control knees. These data provide novel insight into post-traumatic knee injuries that may be signs of early OA pathogenesis.

Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (µCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries.

Cortical and trabecular bone in the femoral neck both contribute to proximal femur failure load prediction.

UNLABELLED: We examined the contributions of femoral neck cortical and trabecular bone to proximal femur failure load. We found that trabecular bone mineral density explained a significant proportion of variance in failure load after accounting for total bone size and cortical bone mineral content or cortical area. INTRODUCTION: The relative contribution of femoral neck trabecular and cortical bone to proximal femur failure load is unclear. OBJECTIVES: Our primary objective was to determine whether trabecular bone mineral density (TbBMD) contributes to proximal femur failure load after accounting for total bone size and cortical bone content. Our secondary objective was to describe regional differences in the relationship among cortical bone, trabecular bone, and failure load within a cross-section of the femoral neck. MATERIALS AND METHODS: We imaged 36 human cadaveric proximal femora using quantitative computed tomography (QCT). We report total bone area (ToA), cortical area (CoA), cortical bone mineral content (CoBMC), and TbBMD measured in the femoral neck cross-section and eight 45 degrees regions. The femora were loaded to failure. RESULTS AND OBSERVATIONS: Trabecular bone mineral density explained a significant proportion of variance in failure load after accounting for ToA and then either CoBMC or CoA respectively. CoBMC contributed significantly to failure load in all regions of the femoral neck except the posterior region. TbBMD contributed significantly to failure load in all regions of the femoral neck except the inferoanterior, superoposterior, and the posterior regions. CONCLUSION: Both cortical and trabecular bone make significant contributions to failure load in ex vivo measures of bone strength.

Tibial geometry is associated with failure load ex vivo: a MRI, pQCT and DXA study.

UNLABELLED: We studied the relations between bone geometry and density and the mechanical properties of human cadaveric tibiae. Bone geometry, assessed by MRI and pQCT, and bone density, assessed by DXA, were significantly associated with bone's mechanical properties. However, cortical density assessed by pQCT was not associated with mechanical properties. INTRODUCTION: The primary objective of this study was to determine the contribution of cross-sectional geometry (by MRI and pQCT) and density (by pQCT and DXA) to mechanical properties of the human cadaveric tibia. METHODS: We assessed 20 human cadaveric tibiae. Bone cross-sectional geometry variables (total area, cortical area, and section modulus) were measured with MRI and pQCT. Cortical density and areal BMD were measured with pQCT and DXA, respectively. The specimens were tested to failure in a four-point bending apparatus. Coefficients of determination between imaging variables of interest and mechanical properties were determined. RESULTS: Cross-sectional geometry measurements from MRI and pQCT were strongly correlated with bone mechanical properties (r(2) range from 0.55 to 0.85). Bone cross-sectional geometry measured by MRI explained a proportion of variance in mechanical properties similar to that explained by pQCT bone cross-sectional geometry measurements and DXA measurements. CONCLUSIONS: We found that there was a close association between geometry and mechanical properties regardless of the imaging modality (MRI or pQCT) used.

Femoral neck cortical geometry measured with magnetic resonance imaging is associated with proximal femur strength.

INTRODUCTION: Magnetic resonance imaging (MRI) is a promising medical imaging technique that we used to assess femoral neck cortical geometry. OBJECTIVES: Our primary objective was to assess whether cortical bone in the femoral neck assessed by MRI was associated with failure load in a simulated sideways fall, with and without adjustment for total bone size. Our secondary objective was to assess the reliability of the MRI measurements. MATERIALS AND METHODS: We imaged 34 human cadaveric proximal femora using MRI and dual-energy X-ray absorptiometry (DXA). MRI measurements of cross-sectional geometry at the femoral neck were the cortical cross-sectional area (CoCSA(MRI)), second area moment of inertia (x axis; Ix(MRI)), and section modulus (x axis; Zx(MRI)). DXA images were analyzed with the standard Hologic protocol. From DXA, we report the areal bone mineral density (aBMD(DXA)) in the femoral neck and trochanteric subregions of interest. The femora were loaded to failure at 100 mm/s in a sideways fall configuration (15 degrees internal rotation, 10 degrees adduction). RESULTS AND OBSERVATIONS: Failure load (N) was the primary outcome. We observed that the femoral neck CoCSA(MRI) and Ix(MRI) were strongly associated with failure load (r (2)=0.46 and 0.48, respectively). These associations were similar to those between femoral neck aBMD and failure load (r (2)=0.40), but lower than the associations between trochanteric aBMD and failure load (r (2)=0.70). CONCLUSION: We report that MRI holds considerable promise for measuring cortical bone geometry in the femoral neck and for predicting strength at the proximal femur.