Update on Imaging-Based Measurement of Bone Mineral Density and Quality

Abstract

Purpose of Review

Patients with inflammatory arthropathies have a high rate of fragility fractures. Diagnostic assessment and monitoring of bone density and quality are therefore critically important. Here, we review standard and advanced techniques to measure bone density and quality, specifically focusing on patients with inflammatory arthropathies.

Recent Findings

Current standard procedures are dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). DXA-based newer methods include trabecular bone score (TBS) and vertebral fracture assessment (VFA). More advanced imaging methods to measure bone quality include high-resolution peripheral quantitative computed tomography (HR-pQCT) as well as multi-detector CT (MD-CT) and magnetic resonance imaging (MRI). Quantitative ultrasound has shown promise but is not standard to assess bone fragility.

Summary

While there are limitations, DXA remains the standard technique to measure density in patients with rheumatological disorders. Newer modalities to measure bone quality may allow better characterization of bone fragility but currently are not standard of care procedures.

Introduction

Rheumatic diseases are very frequently associated with significant bone loss related to the inflammatory disorder itself, therapies that induce bone loss—in particular corticosteroids—and reduced physical activity. Fragility fractures are therefore frequently observed in rheumatic diseases. Optimal management includes measurement of bone density and quality to diagnose fracture risk and monitor osteoporosis-specific therapies. Bone loss found in rheumatoid arthritis, for example, results in an increased risk of osteoporotic fractures in all age groups, men and women, as well as various anatomic sites compared with controls with an overall relative risk of 2.25 (95% CI 2.25–3.83) [1•].

This review article will focus on standard and advanced techniques to measure bone density and quality in patients with inflammatory rheumatological arthropathies. We will cover dual-energy X-ray absorptiometry (DXA), including trabecular bone score (TBS), quantitative computed tomography (QCT), quantitative ultrasound (QUS), high-resolution peripheral quantitative computed tomography (HR-pQCT), multi-detector CT (MD-CT), and magnetic resonance imaging (MRI) as well as advanced technologies to analyze bone quality using volumetric datasets.

Specific Considerations for Measuring Bone Mineral Density and Quality in Rheumatic Diseases

In inflammatory arthropathies, pro-inflammatory cytokines are responsible for osteoclast activation, stimulating bone resorption while simultaneously suppressing bone formation [2•]. This is particularly pronounced in the joints and typically associated with synovial hyperplasia. Eventually, this leads to periarticular osteopenia and erosive bone changes. Juxtaarticular osteopenia tends to be more severe in rheumatoid arthritis than in other inflammatory arthropathies such as psoriatic arthritis.

Systemic bone loss is driven by chronic systemic inflammation, reduced physical activity, and anti-inflammatory medications especially glucocorticoids [3]. Interestingly, however, glucocorticoids induce rapid bone loss and a significant increase in fracture risk, particularly fractures of the vertebral bodies, which cannot be fully explained by any decrease in BMD measured with DXA [4]. Measures of bone structure and marrow composition have therefore been proposed to better characterize fracture risk in patients with glucocorticoid therapy [4, 5].

DXA also has limitations in patients with ankylosing spondylitis (AS), in particular in advanced disease where measurements of the spine in the anteroposterior projection are not reliable and may give falsely elevated results due to syndesmophyte formation and ligamentous ossifications [6]. Alternative methods have been proposed to measure bone strength in these patients including HR-pQCT [6, 7]. Similar issues have been found with advanced degenerative disease of the spine and diffuse idiopathic skeletal hyperostosis (DISH), where QCT may be preferable to DXA to measure fracture risk [8].

Diagnostic Techniques to Measure Bone Mineral Density

Dual-Energy X-ray Absorptiometry

Currently, DXA is the standard technique to measure bone mineral density. The most frequently used measurement sites are the proximal femur, the lumbar spine, and the distal radius. The measurements have a low radiation dose (effective dose adult spine DXA 0.013 mSv and hip DXA 0.009 mSv compared with a lumbar spine radiograph 0.7 mSv [9]). DXA measurements also have a low precision error (short-term precision spine 1.3%, total hip 1.2%, and femoral neck 1.4%) [10].

For many years, DXA has been the standard to define osteoporosis and osteopenia [11]; this definition is based on T-scores, which compare the BMD of an individual with a young normal reference population. A T-score of − 2.5 and lower, i.e., 2.5 or more standard deviations below a young normal reference population, is defined as osteoporosis, while a T-score between − 1.1 and − 2.4 is defined as osteopenia. A T-score of − 1.0 and higher is considered normal. Reference populations are specific to gender and race, and reference data are built into the DXA analysis software from information entered by the technologist performing the test. The World Health Organization (WHO) definition originally applied only to postmenopausal women but according to the International Society of Clinical Densitometry (ISCD) guidelines, these definitions may also be used for men older than 50 [12-14]. Figure 1 shows a DXA spine image of a patient with rheumatoid arthritis and BMD in the osteoporotic range. In addition, the ISCD has introduced guidelines for DXA of premenopausal women, men younger than 50, and children [12-14]. In these populations, Z-scores are used which compare individual BMD measurements with age-matched reference populations; a Z-score lower than − 2 is defined as “bone mineral density below the expected range for age”. In these younger populations, the terms osteopenia or osteoporosis are not used to classify BMD measurements.

Fig. 1.

79-year-old man with a 25-year history of rheumatoid arthritis (RA). The DXA image of the lumbar spine (a) shows mild multilevel degenerative changes. A BMD of 0.762 g/cm² was measured, which corresponds to a T-score of − 3.0. The radiograph of the right hand (b) shows advanced fusion of the carpal bones consistent with the long history of RA

DXA is also used for monitoring therapy. The least significant change that can be measured directly depends on the precision error [15]. In general, using DXA of the spine and hip, a change in BMD of approximately 5% shows a therapy effect.

It should also be noted that DXA has a number of limitations that need to be considered. Since DXA measures BMD in a projectional image, the measurement is sensitive to degenerative changes of the spine and overlying structures such as aortic calcification, which will result in an overestimation of BMD, especially in older men but also in patients with AS and extensive syndesmophytes. Moreover, because density measurements are areal, BMD will be underestimated in patients who are small and overestimated in patients who are tall. Further, due to its projectional nature, DXA cannot differentiate trabecular from cortical BMD. This can be problematic when trying to detect compartment-specific bone changes common in patients with rheumatological disorders, for example, glucocorticoid-induced cortical porosity. Recently, however, DXA-based techniques have been developed that allow to differentiate trabecular and cortical compartments in DXA image datasets. These are based on statistical 3D shape and density models of the proximal femur built from a database of QCT scans, which are registered to hip DXA scans [16, 17].

Several large studies have shown that DXA BMD measurements have limitations in differentiating patients with and without prevalent vertebral fractures, in predicting new fragility fractures, and in monitoring therapy [18-21]. For example, Siris et al. showed in 149,524 white postmenopausal women aged 50–104 years using peripheral DXA measurements that 82% of the women with new fragility fractures had T-scores higher than − 2.5 [21].

Given these limitations of DXA BMD, the FRAX® fracture risk assessment tool (http://www.sheffield.ac.uk/FRAX/) [22-24] was developed, which incorporates femoral neck BMD and additional clinical risk factors such as therapy with glucocorticoids, history of rheumatoid arthritis, previous fracture, fractured hip of a parent, as well as current smoking, alcohol, and secondary osteoporosis. FRAX® provides a 10-year probability risk of a hip or major osteoporosis-related fracture. In patients who are osteopenic, osteoporosis-specific therapy is recommended if the hip fracture risk is ≥ 3% or the risk of a major fracture is ≥ 20% [25]. FRAX is generally not used if BMD is normal or if patients have osteoporotic BMD.

The ISCD official positions from 2019 (www.iscd.org/official-positions/2019-iscd-official-positions-adult/) provide detailed information on indications for BMD testing, which include age 65 and older in women and 70 and older in men. In younger patients, BMD testing is recommended if the patients have risk factors for low bone mass such as prior fracture, high-risk medication, and diseases associated with bone loss. The American College of Radiology (ACR) Appropriateness Criteria on osteoporosis and bone mineral density also include rheumatoid arthritis and other inflammatory arthritides as indications for BMD measurements in premenopausal women and men 20–50 years of age [26].

Trabecular Bone Score

Given the limitations of bone density measurements, researchers have developed tools to assess not simply density but measures of bone architecture. Most of these efforts have focused on volumetric methods based on high-resolution CT or MRI, but low-cost alternatives have also been investigated. Thus, researchers have used standard (projectional) DXA images of the lumbar spine and calculated measures of gray-level texture to define a trabecular bone score (TBS) [27]. TBS uses the gray value of each pixel as well as the information on the degree of spatial dependency for each pixel and its neighboring pixels to extract for each vertebra a variogram as the sum of the squared gray-level differences between pixels at a specific distance. TBS (unitless) is then calculated as the slope of the log-log transform of this variogram with the slope representing the rate of gray-level amplitude variations [28].

A high number of pixel-gray value variations and therefore a steep variogram slope with a high TBS value are found in dense trabecular bone structure, while more porous, osteoporotic trabecular bone produces a low TBS value [28, 29]. TBS reports provide unitless values for the L1-4 vertebra separately and for the total lumbar spine. As with BMD measurements, abnormal or fractured vertebrae are excluded from the analysis. A number of clinical studies demonstrated that low TBS values were associated with increased prevalence and incidence of fragility fractures in postmenopausal women and in older men [30-33] and that the predictive ability of TBS was independent of clinical risk factors, FRAX, and DXA BMD [30]. According to McCloskey, a TBS of > 1.31 is considered normal bone, 1.23 to 1.31 is partially degraded, and < 1.23 is degraded bone [34].

TBS is also included in the ISCD official positions from 2019 (www.iscd.org/official-positions/2019-iscd-official-positions-adult/) stating its association with vertebral, hip, and major osteoporotic fractures in postmenopausal women and men over 50 years. However, there are clear recommendations not to use TBS alone for treatment recommendation, and the role of TBS in monitoring antiresorptive therapy is unclear. A recent scientific article investigated clinical variables to find out which patients might experience the greatest benefit from TBS measurements [35]; among these were glucosteroid use and to a lesser extent rheumatoid arthritis. Another study found that in patients with rheumatoid arthritis, TBS measured at the lumbar spine had a better discrimination value than lumbar spine BMD, and similar to femoral neck BMD, in differentiating patients with and without vertebral fractures [36].

Vertebral Fracture Assessment and Detection of Atypical Fractures

It should be noted that DXA has also been used as a diagnostic and not quantitative method by using the same machine to create images to detect and semiquantitatively assess vertebral fractures and to document atypical femur fractures related to osteoporosis therapy. Vertebral fracture assessment (VFA) is typically performed to diagnose asymptomatic vertebral fractures and the scans cover the entire thoracic and lumbar spine. VFA studies may be particularly useful in people with rheumatic diseases, particularly in rheumatoid arthritis and AS, in whom vertebral fractures are frequently found [37].

The official positions of the ISCD for detection of atypical fractures have recently been published [38]. Different DXA imaging algorithms have been described to image the femora to look for focal periosteal and endosteal thickening as well as the presence of a stress fracture (lucent) line at the lateral cortex.

Quantitative CT

QCT was developed for BMD measurements prior to DXA and though it is currently much less frequently used than DXA, it has some pertinent advantages over DXA. Most importantly, QCT allows true volumetric measurements of the lumbar spine and proximal femur, which are independent of body size, and QCT is able to separate trabecular and cortical compartments. It has been shown previously that compartment-specific measurements are more sensitive to therapy than combined trabecular/cortical measurements as in DXA [39]. But there are also some notable disadvantages of QCT, which include the higher radiation dose (0.06–2.9 mSv) [9].

QCT is typically performed at the lumbar spine (L1-3) and the proximal femur. At the spine, single slice or volumetric techniques are used, covering a mid-vertebral region or the entire vertebral body. Exams are mostly performed with calibration phantoms, which allow the conversion from Hounsfield units into mg hydroxyapatite/cm³ (Fig. 2). More recently, phantomless acquisition methods are available that use fat and muscle for calibration. To interpret the quantitative measurements, absolute BMD values and not T-scores are used, according to the American College of Radiology Practice Parameter for the Performance of Musculoskeletal Quantitative Computed Tomography (Revised 2018 version). (The American College of Radiology will be abbreviated ACRad to distinguish it from the American College of Rheumatology.) A BMD value above 120 mg/ml is defined as normal BMD, 80–120 mg/ml as osteopenia, and below 80 mg/ml as osteoporosis. For the hip, the 3D measurements are transformed into 2D measurements (CTXA) analogous to the hip DXA image and given the similarity of CTXA and DXA measurements, T-scores can be used to interpret the findings as in DXA [40]. Per ACRad practice parameters, in premenopausal women, men younger than 50, and children Z-scores are used, with a Z-score of less or equal to − 2.0 considered to be below the expected range for age.

Fig. 2.

74-year-old woman with a history of rheumatoid arthritis and severe fracture deformity of T12. A volumetric QCT is shown with an axial source image with the calibration phantom and an oval region of interest in the L1 vertebral body (a) as well as sagittal (b) and coronal (c) reconstructions demonstrating the volume that was measured. BMD in L1 was 68.6 mg/cc and L2 76.1 mg/cc consistent with osteoporotic BMD according to American College of Radiology practice guidelines

QCT is beneficial for some rheumatological disorders such as AS and DISH. For example, a study comparing DXA and QCT in older men with DISH demonstrated that QCT was better suited to differentiate men with and without vertebral fractures [8]. Another study comparing DXA and QCT in AS found that with QCT, a decrease in vertebral trabecular bone density could already be observed in the initial disease stages and that in advanced ankyloses in the vertebral region (substantial syndesmophytes), QCT was superior to document bone loss [41]. It has also been shown that trabecular measurements of spine BMD using QCT are not influenced by osteoarthritis of the spine and that in patients with advanced osteoarthritis, QCT may be superior to DXA [42]. Figure 2 shows a QCT study of a patient with rheumatoid arthritis, a severe T12 fracture, and osteoporotic BMD at the lumbar spine.

Quantitative Ultrasound

QUS is an inexpensive, nonionizing technique which is typically performed at peripheral regions such as the forearm or calcaneus. The literature supports QUS as a predictor of fracture risk in osteoporotic populations, and further suggests that QUS may provide information on bone quality beyond simple bone mass [43, 44]. In a recent study of 60 normal adults, a US derived bone measurement correlated well to DXA derived BMD at the 1/3 region of the distal radius [45]. The device used in this study was recently granted FDA approval for clinical use. QUS continues to be limited by a lack of standardization, both in terms of technology and technical parameters evaluated (e.g., broadband ultrasound attenuation, speed of sound, stiffness index, amplitude-dependent speed of sound, and bone transmission time) and anatomic sites evaluated (e.g., calcaneus, tibia, radius, phalanges) [46]. However, if DXA is not available or cannot be done, the ISCD official position is that pharmacologic treatment can be initiated if fracture probability, using device-specific thresholds and in conjunction with clinical risk factors, is sufficiently high (www.iscd.org/official-positions/2019-iscd-official-positions-adult).

A recent meta-analysis conducted to assess the role of QUS in inflammatory rheumatic diseases came to the conclusion that the current literature does not support the substitution of QUS for DXA in the diagnosis and monitoring of osteoporosis in rheumatic diseases [47•]. For rheumatoid arthritis, the authors stated that QUS has a moderate to strong correlation with DXA and good discriminatory performance in differentiating osteoporotic individuals and controls, but conflicting data were found on the use of QUS in the early disease process and in corticosteroid-induced osteoporosis [47•].

Diagnostic Techniques to Measure Bone Quality

As evidence has emerged that additional factors beyond BMD are important in the evaluation of bone health and fracture risk, diagnostic techniques to measure bone quality have been developed and validated. However, compared with standardized BMD measurements, which are part of clinical routine, clinical bone quality evaluations are still in development and, for the most part, remain research tools.

Some of these diagnostic techniques use advanced analysis tools based on three-dimensional imaging modalities (such as HR-pQCT, MD-CT, and MRI) that have been developed and optimized to quantify bone geometry, microstructure, and biomechanical parameters. The goal of these techniques is to more accurately predict fractures and more sensitively monitor therapeutic interventions.

High-Resolution Peripheral Quantitative Computed Tomography

Introduced in 2004, HR-pQCT is a small-bore, high-resolution, dedicated extremity CT imaging system, currently available from a single manufacturer (Scanco Medical AG, Brüttisellen, Switzerland). In 15 years since its introduction, installation of HR-pQCT systems worldwide as well as the number of publications and the size of cohort studies has grown exponentially [48-51]. However, at this time, HR-pQCT remains a research tool without FDA approval for use as a clinical diagnostic tool. The first generation of the HR-pQCT (XtremeCT) was limited to imaging the distal leg and foot and the distal forearm and hand, and achieved a spatial resolution of 82 μm (isotropic voxel dimension) in the standard in vivo scan setting, significantly higher than any other available in vivo imaging tool [52]. The newest generation of this device (XtremeCT II) has an improved spatial resolution of 61 μm, and the ability to scan more proximally, including the knee [53]. Because it is limited to peripheral scan locations, the effective radiation dose of HR-pQCT is substantially lower compared with whole body CT and does not involve critical, radiosensitive organs. For a standard distal tibia or distal radius scan, effective dose is less than 5 μSv. For a full knee scan, which requires multiple image stacks, effective dose is less than 50 μSv.

The high resolution, volumetric acquisition protocol of HR-pQCT allows for quantification of volumetric bone mineral density, geometry, and microstructure of trabecular and cortical compartments. For the distal tibia and distal radius evaluation sites, a standard semiautomated segmentation and analysis protocol is provided by the manufacturer. This protocol requires operator oversight, and often manual correction, during the process of identifying periosteal and endocortical boundaries. Based on this semiautomated contouring and segmentation process, the trabecular and cortical compartments are identified for subsequent densitometric, morphometric, and biomechanical analyses. A calibration phantom containing a series of hydroxyapatite-polymer mixtures is scanned to generate a calibration curve in order to output volumetric BMD data in units of mgHA/cm³. Volumetric BMD is reported for the whole bone as well as trabecular and cortical compartments individually. Within the trabecular compartment, morphometric indices describing trabecular thickness, number, separation, and heterogeneity, as well as connectivity, structure model index (a measure of the rod or plate-like appearance of the structure), and anisotropy are calculated. Within the cortical compartment, cortical thickness and porosity are calculated. For other anatomic sites—for example, the knee, hand, or foot—customized segmentation and analysis strategies have been developed [54, 55]. Of particular interest to the field of rheumatology, there are recent efforts by the Study Group for Xtreme-CT in Rheumatoid Arthritis (SPECTRA) to define and standardize procedures for the evaluation of joint space width and bone erosions [56].

Finite element analysis (FEA) applied to volumetric HR-pQCT data is used to quantify biomechanical properties. Binarized bone volumes are converted to FEA models with operator-determined mechanical properties and failure criteria, and “virtually” loaded in uniaxial compression. Stiffness, elastic modulus, and estimated strength are calculated, as well as cortical load fraction, which indicates the proportion of load borne by the cortical vs. trabecular compartments [57]. These biomechanical models have been validated against mechanical testing in cadaver specimens [58]. HR-pQCT FEA-derived estimates of bone strength performed better than DXA-derived areal BMD at classifying women with and without prior fracture [59] and were shown to predict fracture independent of areal BMD in a prospective study [60].

Reproducibility of HR-pQCT densitometric measures is high, with coefficient of variation < 1%, while microstructural and biomechanical measures typically have a coefficient of variation of 4–5%, and up to ~ 13% for cortical porosity [57, 61-63].

Advanced analyses have been developed by the user community. Topological analyses including individual trabecular segmentation (ITS) [64] and cortical pore topology [65] have been applied to provide insight into microstructural alterations in response to aging and disease. Figure 3 depicts the ability of HR-pQCT imaging and cortical pore analysis to visualize and quantify the impact of 6 weeks of disuse on cortical bone porosity. Trabecular and cortical subregional analyses have been developed to provide spatially-resolved information [67]. Taking this to a more detailed level, statistical parametric mapping has been applied to HR-pQCT [68].

Fig. 3.

Healthy 35-year-old male undergoing anterior cruciate ligament reconstruction and meniscus repair, instructed to remain non-weight-bearing for 6 weeks post-procedure. The distal tibia was imaged by HR-pQCT at two time points: just prior to surgery (left) and after 6 weeks of non-weight-bearing (right). Volumetric reconstructions of the cortical compartment, with porosity highlighted in red, are shown on the top row. Cross-sectional grayscale images are shown on the bottom row. HR-pQCT images and porosity analysis enable visualization and quantification of changes in bone microstructure over the 6-week disuse period [66]

A number of clinical studies have demonstrated the utility of HR-pQCT measures in fracture prediction as well as monitoring of therapeutic intervention. In aging populations, cortical and trabecular microarchitecture [50] as well as volumetric BMD and biomechanical measures from FEA [69] have been shown to predict incident fracture independent of DXA areal BMD and clinical risk factors. In patients with rheumatoid arthritis, erosion volume, cortical interruptions, and microstructural parameters have been demonstrated to be sensitive metrics for the evaluation of treatment response [70].

There are several disadvantages of HR-pQCT; most notably that it is not approved for clinical use at this time. Additionally, it is limited to peripheral skeletal sites and therefore can provide no direct insight into bone quality at the lumbar spine or proximal femur—common sites for osteoporotic fragility fractures. Persistent issues include motion artifacts, which sometimes limit morphological analysis of bone microstructure [71], and a lack of consensus on imaging protocols, particularly in imaging children and adolescents [72, 73].

Multi-Detector CT

MD-CT provides superior spatial resolution compared with traditional whole-body spiral CT scanners and is standard in clinical use. An advantage of MD-CT compared with HR-pQCT is access to central anatomic sites at greatest risk for fragility fractures, such as the spine and proximal femur, where monitoring of disease and therapy may be most efficient. However, the radiation exposure required to achieve high spatial resolution and adequate image quality is substantial [9, 74]. Compared with the effective dose of HR-pQCT or an adult DXA spine exam (0.001–0.05 mSv) and that of a conventional QCT spine exam (0.06–0.3 mSv), the radiation exposure of a high-resolution MD-CT vertebral microstructure protocol is orders of magnitude higher (~ 3 mSv) [74, 75]. Importantly, low-dose MD-CT techniques are being developed, for example, iterative reconstruction algorithms or sparse sampling, which provide reduction in radiation exposure while maintaining high diagnostic accuracy [76, 77].

With slice thickness on the order of 500 μm and in-plane resolution of ~ 150 μm, imaging of trabecular or cortical microstructure with MD-CT is certainly limited and subject to substantial partial volume effects. However, for certain microstructural parameters obtained with MD-CT—in particular plate-rod ratio [78]—good correlations have been achieved with values obtained from gold standard microCT images [79].

Clinical studies have demonstrated the utility of MD-CT in diagnosing existing fractures with high specificity and sensitivity [80]. Further, MD-CT-derived structure measures at the proximal femur and lumbar spine have been shown to improve differentiation of fracture patients from normal controls [81]. MD-CT was also shown to be well-suited for monitoring teriparatide-associated changes of vertebral microstructure [74]. Prediction of incident vertebral fracture has been demonstrated using MD-CT-based FEA [82].

Magnetic Resonance Imaging

Advances in MRI software and hardware including 3T and 7T magnets and improved coil design have enabled improved skeletal structural imaging. Lack of radiation makes MRI attractive for both clinical and scientific studies. However, historically, the technique has been used mainly for peripheral imaging. Recent advances in image acquisition have resulted in improved image quality even at central sites. At the proximal femur—a particularly challenging site due to the soft tissue around the femur and thus large distance from the radiofrequency coil to the femur—depiction of trabecular structure with minimal blurring and high SNR efficiency has been achieved (Fig. 4) [83, 84]. Calibration and validation studies have demonstrated that MR-derived trabecular structure measures correlate with histology, microCT, and biomechanical strength derived from in vitro studies [85-88]. MRI-based texture measures are also used to represent bone quality [89]. MRI texture analysis quantifies the organizational pattern of pixel grayscales representing the underlying tissue; the spatial distribution of grayscales can reflect the structural properties of the imaged tissue. This approach is similar to TBS from DXA; however, rather than using low resolution projectional DXA data, in MRI-based texture analysis, results are derived from three-dimensional image volumes with high anatomic detail.

Fig. 4.

High-resolution MRI of the proximal femur in two postmenopausal women, one a healthy control (left) and one with osteoporosis and history of fragility fracture at a remote site (right). Courtesy of Roland Krug, PhD, UCSF

Over the last decade, technical advancements in MRI acquisition have enabled visualization as well as microstructural and compositional analysis of cortical bone, previously impossible with standard MRI acquisition. This has been accomplished using ultra-short echo time (UTE) imaging. UTE imaging allows detection of signal components with T2 relaxation times on the order of a few hundred microseconds. In bone, this signal is derived from “free water” residing in the osteonal and lacuno-cannalicular networks and from “bound water” within the bone matrix [90]. Techawiboonwong et al. validated bone water imaging (i.e., the measurement of water in cortical bone) using a UTE sequence in cortical bone specimens and studied the tibial midshaft in premenopausal and postmenopausal females and patients on hemodialysis [91]. The quantitative analysis showed that bone water content was 135% higher in the patients on maintenance dialysis than in the premenopausal women and 43% higher than in the postmenopausal women. Because bone water exists primarily in the pore system of cortical bone, bone water content is thought to provide a surrogate measure for cortical porosity. Accordingly, the bone water content results align with the expected porosity differences in these three populations. More recently, Rajapaske et al. presented a calculation method and validation of a metric-termed porosity index. In ex vivo bone specimens, porosity index was well correlated with microCT-based porosity quantification [92].

Despite these advancements in MRI bone imaging, numerous challenges remain. Spatial resolution remains above the range of trabecular and cortical microstructural dimensions (resolution in plane 0.15–0.3 mm², slice thickness 0.3–1 mm). Partial volume artifacts due to limited resolution combined with susceptibility artifacts result in systematic bias in structure parameter values; in particular, the morphological parameter trabecular bone volume fraction and trabecular thickness were demonstrated to exhibit large discrepancies compared with HR-pQCT (MR/HR-pQCT = 3–4) [52]. In addition, long acquisition times make MRI susceptible to motion artifacts, which negatively impact structural analysis.

MRI-derived bone quality measures have been shown to provide additional information to BMD in differentiating individuals with and without fragility fractures [93-97]. Longitudinal studies using MRI-derived trabecular microarchitecture measures have demonstrated the feasibility of the technique in monitoring the effect of therapeutic interventions [98] [99]. Folkesson et al. found longitudinal changes in MR-derived bone microarchitecture due to bisphosphonate therapy in perimenopausal women treated for 24 months with alendronate [100]. In a prospective longitudinal study of a cohort undergoing high tibial osteotomy, MRI was used to quantify changes in subchondral bone following surgery, finding both a reversal of previous subchondral abnormalities and a positive association of this subchondral structural normalization with functional outcome [101].

Conclusion

Patients with inflammatory rheumatological disorders have a high rate of fragility fractures. Diagnostic assessment of bone density and quality is therefore critically important. The standard assessment tool is DXA and though it does have some limitations, it provides a good general assessment, which can be augmented through VFA and TBS measurements. QCT is more of a problem solver in particular in patients with AS and DISH and though similar in diagnostic performance as DXA, it is not as frequently used anymore. Newer techniques to assess bone quality have a role in helping to better characterize bone fragility in areas where bone density has limitations, such as in patients with corticosteroid therapy, but they are currently not a clinical standard.