Multiparametric 3-D analysis of bone and joint space width at the knee from weight bearing computed tomography.

Objective: Computed tomography (CT) can deliver multiple parameters relevant to osteoarthritis. In this study we demonstrate that a 3-D multiparametric approach at the weight bearing knee with cone beam CT is feasible, can include multiple parameters from across the joint space, and can reveal stronger relationships with disease status in combination. Design: 33 participants with knee weight bearing CT (WBCT) were analysed with joint space mapping and cortical bone mapping to deliver joint space width (JSW), subchondral bone plate thickness, endocortical thickness, and trabecular attenuation at both sides of the joint. All data were co-localised to the same canonical surface. Statistical parametric mapping (SPM) was applied in uni- and multivariate models to demonstrate significant dependence of parameters on Kellgren & Lawrence grade (KLG). Correlation between JSW and bony parameters and 2-week test-retest repeatability were also calculated. Results: SPM revealed that the central-to-posterior medial tibiofemoral joint space was significantly narrowed by up to 0.5 mm with significantly higher tibial trabecular attenuation up to 50 units for each increment in KLG as single features, and in a wider distribution when combined (p<0.05). These were also more strongly correlated with worsening KLG grade category. Test-retest repeatability was subvoxel (0.37 mm) for nearly all thickness parameters. Conclusions: 3-D JSW and tibial trabecular attenuation are repeatable and significantly dependent on radiographic disease severity at the weight bearing knee joint not just alone, but more strongly in combination. A quantitative multiparametric approach with WBCT may have potential for more sensitive investigation of disease progression in osteoarthritis.

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density.

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 µg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Femoral neck trabecular bone: loss with aging and role in preventing fracture.

Hip fracture risk rises 100- to 1000-fold over six decades of age, but only a minor part of this increase is explained by declining BMD. A potentially independent cause of fragility is cortical thinning predisposing to local crushing, in which bone tissue's material disintegrates at the microscopic level when compressed beyond its capacity to maintain integrity. Elastic instability or buckling of a much thinned cortex might alternatively occur under compression. In a buckle, the cortex moves approximately at right angles to the direction of load, thereby distorting its microstructure, eventually to the point of disintegration. By resisting buckling movement, trabecular buttressing would protect the femoral neck cortex against this type of failure but not against crushing. We quantified the effect of aging on trabecular BMD in the femoral neck and assessed its contribution to cortical elastic stability, which determines resistance to buckling. Using CT, we measured ex vivo the distribution of bone in the midfemoral necks of 35 female and 33 male proximal femurs from cases of sudden death in those 20-95 yr of age. We calculated the critical stress sigma(cr), at which the cortex was predicted to buckle locally, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall. Using long-established engineering principles, we estimated the amount by which stability or buckling resistance was increased by the trabecular bone supporting the most stressed cortical sector in each femoral neck. We repeated these measurements and calculations in an age- and sex-matched series of femoral necks donated by women who had suffered intracapsular hip fracture and controls, using histological measurements of cortical thickness to improve accuracy. With normal aging, trabecular BMD declined asymmetrically, fastest in the supero-lateral one-half (in antero-posterior projection) of the trabecular compartment. When viewed axially with respect to the femoral neck, the most rapid loss of trabecular bone occurred in the posterior part of this region (supero-posterior [S-P]), amounting to a 42% reduction in women (34% in men) over five decades of adult age. Because local cortical bone thickness declined comparably, age had no significant effect on the relative contributions of cortical and trabecular bone to elastic stability, and trabecular bone was calculated to contribute 40% (in men) and 43% (in women) to the S-P cortex of its overall elastic stability. Hip fracture cases had reduced elastic stability compared with age-matched controls, with a median reduction of 49% or 37%, depending on whether thickness was measured histologically or by CT (pQCT; p < 0.002 for both). This effect was because of reduced cortical thickness and density. Trabecular BMD was similar in hip fracture cases and controls. The capacity of the femur to resist fracture in a sideways fall becomes compromised with normal aging because cortical thickness and trabecular BMD in the most compressed part of the femoral neck both decline substantially. This decline is relatively more rapid than that of femoral neck areal BMD. If elastic instability rather than cortical crushing initiates the fracture event, interventions that increase trabecular bone in the proximal femur have great potential to reduce fracture risk because the gradient defining the increase in elastic stability with increasing trabecular BMD is steep, and most hip fracture cases have sufficient trabecular bone for anabolic therapies to build on.