Introduction
Osteoporosis is a disease of the skeletal system characterised by reduced bone strength and increased risk of fracture. Bone strength is a crucial indicator of bone health, taking into account both bone density and quality as key factors. Bone density measurements are the primary basis for the diagnosis of osteoporosis (OP). The conventional tool for assessing bone density is dual-energy X-ray absorptiometry (DXA), but bone quality is under-assessed. However, bone quality is a comprehensive indicator that includes various factors such as microstructures of bone, bone turnover rate, degree of accumulated bone damage, mineralisation level, and matrix properties. There are significant challenges in detecting this indicator in clinical practice. In recent years, with the development of imaging and diagnostic techniques for osteoporosis, new imaging techniques have been rapidly developed, especially three-dimensional quantitative computed tomography (QCT), high-resolution magnetic resonance imaging (HR-MRI), and quantitative ultrasound (QUS), which provide technical support for the further detection of biomechanical parameters, such as bone microarchitecture and geometric characteristics of bone.
Bone mineral density measurement technology
Dual X-ray absorptiometry (DXA)
DXA is the most commonly used method of bone densitometry, which measures two-dimensional bone mineral density (areal BMD) [1]. Commonly used measurement sites are the hip, spine, and forearm, and its advantages include image resolution, high precision, short scanning time, low radiation dose, and ease of operation. Bone densitometry provides an accurate picture of the mineral content of bone and is currently considered the gold standard for the diagnosis of osteoporosis, but it still has some limitations. For example, dual-energy X-ray absorptiometry (DXA) measures bone mineral density (BMD) using projected images, which are sensitive to degenerative changes in the spine, osteophytes, and overlying structures (such as aortic calcification). These changes can lead to an overestimation of BMD, particularly in older men. In addition, in the early stage of osteoporosis, trabecular bone rather than cortical bone is the first to be lost, and DXA is unable to distinguish cortical bone from cancellous bone. The regional BMD measured by DXA is limited by the depth of measurement, and volumetric BMD cannot be obtained, and it is affected by the size of the bones, so that the BMD of patients with short stature may be underestimated and the BMD of patients with tall stature may be overestimated. At the same time, the thickness or weight of the body will also have some influence on the BMD measured by DXA, and the diagnostic accuracy will be reduced in obese patients. Although DXA is widely used in paediatrics, the size and shape of children’s bones are constantly changing, and bone age, sexual maturity, and the degree of skeletal development all influence the interpretation of BMD [2]. The DXA technique, moreover, lacks the capability to assess trabecular bone and cortical bone lacunae, as well as provide insights into bone microstructure. DXA has a high specificity and low sensitivity for fracture prediction and is dependent on the point of diagnosis. Numerous studies have shown that people with normal or even increased BMD are also at risk of fragility fracture, and that BMD only partially reflects bone strength, and cannot effectively evaluate the effect of anti-osteoporosis treatment and the changes in bone structure during treatment. In recent years, the combination of DXA technology and modern computer software has expanded the measurement function of DXA.
PA spine BMD
Currently, PA spine BMD is commonly used in the clinical measurement of lumbar spine bone density. The measurement site includes the vertebral body and its posterior attachment structures. Measurements are susceptible to interference from aortic calcification, degenerative osteoarthropathy, osteophytes, spondylolisthesis, bone scars, and vertebral compression fractures, and osteophytes and degenerative changes of the spine are very common in the elderly population, which limits the utility and sensitivity of PA spine BMD measurements in the elderly. Because the rate of bone loss is affected by age and skeletal site, in perimenopausal and early postmenopausal women, bone loss occurs mainly in the spine; therefore, PA spine BMD may be preferred in perimenopausal and early postmenopausal women in the absence of osteomalacia and osteoarthritis, fracture, calcification, and artefacts [3].
Lateral lumbar BMD
Lateral lumbar spine BMD has high sensitivity for the diagnosis of osteoporosis in the elderly. Currently, orthotopic DXA is commonly used in clinical measurements of lumbar spine bone density. The measurement site includes the vertebral body and its posterior attachment structures. Measurements are affected by vertebral and small joint osteophytes and sclerosis as well as calcification of the abdominal aorta. The choice of lumbar lateral BMD measurement avoids the interference of these factors [4]. The vertebral bodies are rich in cancellous bone and are the site of choice for osteoporotic compression fractures. The spinous processes, transverse processes, and pedicles of the posterior 1/3 of the spine are rich in cortical bone and do not play an important role in osteoporotic compression fractures. Lateral lumbar measurements can exclude the posterior 1/3 of the spine and detect vertebral bone loss early. In addition, with age, the bone density of the anterior part of the vertebral body decreases by about 50% and that of the posterior part by about 25%. Therefore, in elderly patients, the lateral BMD of the vertebral body can better reflect the actual changes in the cancellous bone and the bone mass of the vertebral body itself. Through lateral lumbar BMD accompanied by anteroposterior lumbar BMD, the estimated volume BMD (v BMD) of the lumbar two-dimensional scan, bone mass parameters of the middle area of each vertebral body and the whole vertebral body can be obtained at the same time. It also avoids some interfering factors and improves the sensitivity of diagnosing osteoporosis.
Hip BMD
BMD measurements of the hip are also a common site for clinical bone densitometry. The sites of interest for diagnosing osteoporosis are femoral neck and total hip. It has been found that hip BMD changes more regularly with age and is a good predictor of systemic osteoporosis; its measurement is not affected by osteophytes, calcifications. and artefacts, but it is affected by the angle of rotation of the femur. In general, BMD at the hip is more sensitive than BMD at the lumbar spine in the elderly population. Compared with lumbar and distal forearm BMD, hip BMD is the best predictor of systemic fracture risks [5, 6].
Forearm BMD
Forearm BMD is a DXA measurement of the peripheral skeleton, typically measuring the distal 1/3 of the radius on the unstressed (left) side of the forearm. This has the advantages of ease of use, low radiation exposure, high accuracy, and high sensitivity. The distal 1/3 of the radius is generally chosen as a third measurement site when the hip and spine cannot be measured or interpreted. Bone densitometry on the distal 1/3 of the radius is mainly used in hyperparathyroidism. Primary hyperparathyroidism preferentially affects areas rich in cortical bone, such as the hip and mid-radius, as opposed to the predominantly cancellous bone of the lumbar spine [7]. It was found that distal radius BMD measurements were usually lower than mid-radial BMD measurements and that distal forearm BMD was less prone to calcification and osteophytes, suggesting that mid-radial BMD combined with distal forearm BMD can be used for early detection of bone loss and to reduce the underdiagnosis of osteoporosis, and that distal radius BMD independently predicts radial fractures. Furthermore, in rheumatoid arthritis, peripheral bone density (forearm) may be considered in addition to lumbar spine and hip because localised bone loss is a feature of the disease [8].
Vertebral fracture assessment (VFA)
Lateral images of the thoracolumbar vertebrae obtained by DXA can be used to evaluate vertebral morphology and fracture. The Genant semi-quantitative method and quantitative morphometry are currently the most commonly used methods for clinical assessment of vertebral fractures. VFA software combines the Genant semi-quantitative method and quantitative morphometry to grade vertebral fractures. Vertebral fractures are classified into 4 levels based on the shape of the vertebral body (including wedge, concave, or compression) and the height of the anterior, posterior, and/or medial margins of the vertebral body, as well as the projected area of the vertebral body. In grade 0 (normal), the vertebral body is normal in shape and size; in grade 1 (mild deformity) the height of the anterior margin of the vertebral body is reduced by 20% to 25% and the projected area of the vertebral body is reduced by 10% to 20%; in level 2 (moderate deformity) the height of the anterior margin of the vertebral body is reduced by 25-40% and the projected area of the vertebral body is reduced by 25-40%; and in level 3 (severe deformity) the height of the anterior margin of the vertebral body and the projected area of the vertebral body are reduced by 40% or more. It is generally accepted that a reduction of 40% or more should be considered a fracture at grade 1 or greater, and severe and multiple vertebral fractures indicate a higher risk of further fractures [9, 10]. The VFA is a diagnostic tool used to identify asymptomatic vertebral fractures. It exhibits low radiosity, offers convenient inspection, operates at a fast speed, incurs low costs, and enables one-time imaging. A meta-analysis of the literature revealed no statistically significant difference in consistency, sensitivity, and specificity in the diagnosis of vertebral fragility fractures compared to conventional radiographs [11, 12]. However, in congenital degenerative vertebral changes, spinal degeneration, malignant tumours, and inflammatory diseases, VFA is more time-consuming and less accurate than X-ray. The DXA line-to-line scanning mode using fan-beam technology avoids vertebral deformation (especially in the lumbar spine) caused by the oblique projection of conventional X-ray [13]. Figure 1 shows the difference between conventional DXA and lumbar lateral view combined with VFA testing in the diagnosis of osteoporosis in older women. Conventional DXA diagnosed reduced bone mass in the lumbar spine and hip; lumbar lateral view combined with vertebral fracture assessment (VFA) showed a bone density T-score of –3.5, while VFA showed moderate wedge-shaped changes in the 12th vertebral body of the thoracic spine and moderate biconcave deformity of the 8th thoracic vertebral body. A diagnosis of severe osteoporosis was made [14]. VFA can detect vertebral fractures in patients with normal bone density and correctly assess vertebral fracture severity. BMD combined with VFA reduces the underdiagnosis of osteoporosis in clinical practice, and the International Society for Clinical Densitometry (ISCD) recommends the use of VFA when the T-score is < –1 and the following criteria are met:
- — women ≥ 70 years of age or men ≥ 80 years of age;
- — historical height loss > 4 cm;
- — self-reported but unproven vertebral fracture;
- — glucocorticoid therapy equivalent to ≥ 5 mg of prednisone or equivalent per day for ≥ 3 months. In rheumatic diseases, the VFA is also used to assess vertebral fractures, particularly in rheumatoid arthritis and ankylosing spondylitis, which are commonly associated with vertebral fractures [15].
Trabecular bone score (TBS)
Trabecular bone score (TBS) is an indirect assessment of bone trabecular microarchitecture by assessing grey-scale changes in lumbar spine DXA images with TBS Nsight software. The TBS value is determined solely based on the existing DXA images, eliminating the need for additional imaging examinations [16]. The study findings revealed a significant correlation between TBS values and the state of bone microstructure, specifically pertaining to trabecular number and spacing [17]. Higher TBS values indicate better bone microstructure. TBS can provide independent fracture prediction, unaffected by bone mineral density (BMD) and other clinical risk factors. It can be incorporated into the fracture risk assessment tool (FRAX) to enhance the accuracy of predicting fractures [18]. Compared with BMD, TBS value is not affected by bone hyperplasia, and it is a reliable tool to assess bone quality and predict the risk of osteoporotic fractures [19, 20]. The combination of TBS and BMD provides a more comprehensive risk assessment for fragility fractures in diabetic patients compared to relying solely on BMD measurements. Diabetic patients often exhibit normal or higher BMD levels compared to non-diabetic individuals, making it easy to overlook or delay the diagnosis of high-risk populations for fragility fractures. By incorporating TBS into the evaluation and screening process, particularly in type 2 diabetic patients, this limitation can be effectively addressed [21]. In the diagnosis and assessment of secondary fractures caused by acromegaly, the TBS method demonstrates superiority in assessing the extent of trabecular bone structure deterioration in the lumbar spine compared to BMD. The study demonstrated no statistically significant difference in MBD measurements between patients with acromegaly and healthy subjects, whereas a statistically significant disparity was observed in TBS measurements between the 2 groups. Patients with acromegaly exhibited significantly lower TBS at the lumbar spine compared to healthy subjects. In clinical practice, simultaneous measurement of TBS and BMD can be employed, thereby saving time and cost while avoiding dual exposure of patients to ionising radiation [22]. Meanwhile, TBS is also significantly better than BMD in evaluating the risk of fracture in secondary OP diseases caused by hyperparathyroidism, long-term hormone use, rheumatoid arthritis, Cushing’s syndrome, etc. [23, 24], and the operation of TBS is simple and low-cost. However, there are still limitations in its clinical application. For example, TBS is easily affected by the resolution of DXA images. As the image resolution decreases, TBS increases [25]. In addition, the composition and thickness of the soft tissues around the lumbar spine also affect the accuracy of TBS values, and an increase in the thickness of the soft tissues under the spine leads to a decrease in TBS values [26]. At the same time, there is limited clinical research data on TBS. Currently, most of the TBS study populations are postmenopausal women, and there is a defined threshold for TBS evaluation of bone microarchitecture in postmenopausal women, with TBS values > 1.350 indicating normal bone microarchitecture, TBS values between 1.200 and 1.350 indicating partially degraded bone microarchitecture, and TBS < 1.200 indicating degraded bone microarchitecture [27]. In the future, large-scale epidemiological surveys covering different ages and genders will be needed. TBS, as an emerging technique, is expected to be an effective and convenient clinical tool for assessing the risk of osteoporotic fracture, but further studies are still needed.
Hip structure analysis (HSA)
Hip structure analysis (HAS) is based on DXA scanning images of the proximal femur and computer analysis to obtain the geometric mechanical parameters of the hip structure, through the femoral neck cross-sectional moment of inertia (CSMI), the femoral neck cross-sectional area (CSA), the cross-sectional modulus (SM), the femoral neck width (FNW), the femoral neck axis angle (CSMI), the femoral proximal strength index (FSI), and other mechanical indexes, to predict the bone strength in the region of interest. The analysis is refined and can effectively predict the risk of hip fracture [28–30]. Although HSA analyses many parameters through the geometry of the proximal femur, it can also provide information about the biomechanical and pathophysiological aspects of its fracture. The geometric, morphological, and mechanical parameters of the proximal femur used by different researchers and study subjects are inconsistent, as are the findings obtained [31–33]. The International Society for Clinical Densitometry (ISCD) (https://iscd.org) concluded that the CSA, SM, CSMI, and NSA of the DXA hip geometry parameters do not assess the risk of hip fracture and cannot be used as an indicator for initiating treatment or for assessing the efficacy of treatment. In addition, the main limitations of DXA’s HSA are restricted by the two-dimensional imaging of DXA, and the clinical significance of the HSA parameters remains to be further investigated.
Finite element analysis (FEA)
Finite element analysis (FEA) is a two-dimensional model for evaluating the strength parameters of the femur, first presented in 2013 [34]. FEA uses DXA images of scans of the proximal femur to segment the proximal femur into segments, sub-segments, or even per pixel, measure the femoral surface density and the corresponding femoral length, and then calculate the corresponding volume by software. BMD models create per-pixel stress distribution and stress factor maps that can be used for hip fracture risk assessment [35]. With the increase in the number of elderly patients with osteoporosis, the development of new DXA features, further improvements in DXA fan-beam scanning technology, and the use of multiple detectors, the current use of low-radiation-dose DXA in the measurement and evaluation of human BMD is expanding. However, apart from the relatively mature bone density measurement and body composition analysis, other functions such as HSA, TBS, and FEA detection are mostly limited to preliminary clinical applications or experimental research stages.
Quantitative ultrasound (QUS)
QUS is a non-ionisation technique for detecting BMD using acoustic waves. It has the advantages of simplicity, no radiation damage, high reproducibility, low price, and mobility [36]. Since Longton et al. (2008) used QUS to measure bone tissue for the first time in 1984, the theory, method, and equipment of QUS to measure BMD have been greatly developed [37]. There are 4 types of US transmissions: trabecular transverse transmission, cortical transverse transmission, cortical axial transmission, and pulse-echo measuring devices [38, 40]. Of these, the trabecular transverse transmission is mainly used for measurement of cancellous bone, with the site of detection being the heel bone, and the cortical axial transmission is used for cortical bone detection, with the site of detection being the radius bone [41]. Other sites of measurement by QUS equipment are the phalanges of the fingers, the tibia, and less commonly the femur, as well as the posterior eminences of the spine and the ulna. Among the quantitative ultrasound (QUS) variables in the heel bone, the heel bone has been recognised as a valid site for the use of QUS in OP, and it has also been shown to be a strong predictor of hip fracture and other non-spinal fractures, with performance comparable to that of DXA. QUS measures broadband ultrasound attenuation (BUA) and speed of sound (SOS) in the heel and provides an index known as the quantitative ultrasound index (QUI). BUA assesses an important parameter of bone volume and bone structure, and SOS reflects the stiffness and elasticity of the bone. The QUI provides a comprehensive assessment of bone quality. These QUS parameters provide quantitative information about bone health and correlate with fracture risk [42]. At present, there is no uniform standard for ultrasound diagnosis of osteoporosis, and it is not appropriate to apply the diagnostic standard of T ≤ –2.5 SD of the WHO, whose sensitivity and specificity are not ideal. At present, it is mainly used for the screening of osteoporosis risk groups and the risk assessment of osteoporotic fractures in clinical routine. Each QUS parameter (BUA, SOS, SI, QUI) was individually associated with the risk of different fracture outcomes, and QUS was able to predict fractures independently of FRAX, BMD, and TBS. Research on elderly Chinese men revealed that QUS metrics, including broadband ultrasound attenuation (BUA) and the quantitative ultrasound index (QUI), were closely associated with nonvertebral and major fragility fractures and served as the top predictors for these fractures. A separate case-cohort study of postmenopausal women highlighted that QUS could reliably differentiate between women with and without fractures, with BUA being notably effective in assessing fracture risk. When it came to detecting hip and distal forearm fractures, the quantitative ultrasound index (QUI) T-score and speed of sound (SOS) were found to be the most reliable indicators. Although QUS showed promise in forecasting site-specific fracture risk, the study’s limited sample size calls for additional validation in a larger, prospective study [43, 44]. QUS cannot be used for the diagnosis of osteoporosis or the judgement of drug efficacy. If osteoporosis is suspected, further DXA measurements should be performed. Although QUS currently has limitations in clinical practice, it is also widely used, especially in areas such as paediatrics, rural health centres, and physical examination screening structures. QUS parameters for bone quality assessment are an excellent complement to DXA [45].
Quantitative computer tomography (QCT)
Quantitative computed tomography (QCT) is a method of measuring bone density on the basis of CT scan data, after QCT phantom calibration and professional software analysis. QCT measures volumetric bone mineral density (vBMD) in units of mg/cm3, which is a more sensitive reflection of the changes in bone mineral density. Compared with DXA, QCT measurement is not affected by factors such as spinal hyperplasia, degeneration, and vascular calcification, and it can avoid the false-negative results of planar projection bone densitometry technique caused by the above factors [46]. Also, raw data from QCT can be used for sophisticated image processing to analyse and study bone changes and structural features [47]. QCT includes central QCT, peripheral QCT, high-resolution peripheral quantitative CT (HR-p QCT), and micro-CT, and it has been widely used in clinical and scientific research for osteoporosis health management due to the advantages of its imaging technology [48, 49].
Central quantitative computed tomography (cQCT)
cQCT is a model that uses multiple 2D slices, the centrally described regions of the model are the lumbar spine (especially the L1-3 vertebral body), the proximal femur, and a measure of muscle mass is also provided [50].The cQCT measures vBMD (mg/cm3), improves the sensitivity and accuracy of BMD measurement, and can evaluate bone geometry and biomechanical measurements of bone strength, but it increases the burden of ionising radiation and may cause changes in marrow fat [51]. The findings of various studies have demonstrated that lumbar spine QCT exhibits superior sensitivity in measuring BMD compared to lumbar spine and hip DXA, enabling a more accurate reflection of changes in bone metabolism. Additionally, the vBMD of the hip is comparable to the areal BMD measured by DXA [52–54]. According to the diagnostic criteria of the International Society for Densitometry (ISCD) and the American College of Radiology (ACR), we found that QCT is more sensitive than DXA in detecting osteoporosis [55]. Lumbar spine QCT diagnostic criteria for osteoporosis are as follows: an absolute value of BMD > 120 mg/cm3 is normal; an absolute value of BMD in the range of 80–120 mg/cm3 is low bone mass; and BMD 80 mg/cm3 is osteoporosis [56]. This diagnostic criterion applies to postmenopausal women and older men.
Peripheral quantitative computed tomography (pQCT)
The measurement site of pQCT is mostly the distal radius and tibia, and the measurement results of this site mainly reflect the cortical bone density. Compared with cQCT, pQCT modality has lower radiation load and provides valuable data not only on v BMD, bone geometry, and bone strength, but also on cross-sectional area and muscle density. Also, it can be used to assess the risk of hip fracture in postmenopausal women. Because there is no diagnostic standard at present, it cannot be used for the diagnosis of osteoporosis or the judgement of clinical drug efficacy.
High-resolution peripheral computed tomography (HR-pQCT)
High-resolution peripheral computed tomography (HR-pQCT) is a state-of-the-art three-dimensional (3D) imaging technique that employs semi-automated tissue contouring and segmentation to precisely measure density, morphology, microstructure, and biomechanical properties (such as stiffness and elasticity modulus) using finite element analysis. This cutting-edge technology accurately quantifies volumetric bone mineral density, cortical thickness, and trabecular microarchitecture in neighbouring areas like the distal radius and tibia, additionally evaluating v BMD along with cortical and trabecular microstructure at peripheral sites including the radius or distal tibia. With its resolution of 0.5 mm and effective radiation dose is 3–5 m SV [57, 58], the HR-pQCT technique enables the monitoring of peripheral bone microstructure changes, facilitating early microscopic diagnosis of osteoporosis. It has also been shown that HR-pQCT is statistically significant in the assessment of the efficacy of applied anti-osteoporotic bisphosphonates (e.g. alendronate, risedronate), teriparatide, and denosumab and in the discovery of sensitive sites [59–62]. HR-pQCT assessment has been applied in large-scale epidemiological cohort studies, which have contributed to the understanding of the pathophysiological basis of bone brittleness and to improving the prediction of bone fracture [63, 64]. It was found to be superior to BMD not only in the assessment of bone microstructure in patients with chronic kidney disease (CKD) and in haemodialysis patients, but also in the assessment of bone microstructure in general. Marques et al. found that the quality of the iliac crest bone measured by HR-pQCT was consistent with that obtained by iliac crest biopsy. However, there is still controversy as to whether the assessment of bone quality by iliac crest biopsy is correlated with the assessment of spinal, hip, or peripheral bone quality by HR-p QCT. Currently, due to the limited sample size, a larger prospective study is warranted to establish the potential of HR-pQCT as a replacement for bone biopsy in assessing bone microstructure in future evaluations [65]. The clinical application and investigation of HR-pQCT have also been extended to other metabolic disorders, including drug efficacy assessment, rare skeletal conditions, hand joint imaging, and fracture repair [66, 67]. HR-pQCT has the unique advantage of high spatial resolution in vivo to quantify the microstructure of trabecular and cortical bone, which is of high value in the study of bone quality, especially microstructure [68]. However, HR-pQCT is currently mainly used in research centres and is expensive, and the imaging technique needs to be further standardised. Despite recent recommendations for standardisation in scanning, analysis, quality control, and reporting of results, the future of HR-pQCT in clinical practice requires further research [69].
Micro computed tomography (micro-CT) technology
The resolution of micro computed tomography (micro-CT) has reached 6 µm, and even higher resolution can be obtained if a synchrotron is used. Micro-CT can clearly show the bone trabecular structure, and the bone microstructural parameters obtained correlate well with traditional histological methods [70]. Micro-CT has a high radiation dose and a narrow examination calibre. Currently, it mainly detects isolated specimens or animals. For specimens, micro-CT is usually used only in animal experiments to assess the effects of drugs or diseases on bone microstructure. These basic studies are very helpful for us to understand the occurrence of osteoporosis and to observe its efficacy.
Magnetic resonance imaging (MRI)
MRI technology uses a strong magnetic field and electromagnetic pulse sequence to obtain three-dimensional images, which has the advantages of sensitive signal display and rich post-processing. It can also perform quantitative bone density examination and bone microstructure imaging, which helps in the diagnosis and differentiation of osteoporosis. It is superior to X-ray and CT examination in determining osteoporotic fracture, and there is no X-ray radiation [71]. In recent years, the advantages of various MRI techniques in the field of osteoporosis research have been gradually highlighted [72].
Transverse relaxation time (T2*)
T2* indirectly reflects the morphological structure of bone tissue through the T2* value of the bone marrow. Due to differences in the magnetisation of trabecular bone and bone marrow tissue, the magnetic field at the junction of the two is inhomogeneous, and changes in the shape and structure of the trabecular bone affect the relaxation properties of the surrounding bone marrow, which is manifested as a change in the T2* value of the bone marrow in the gradient echo sequence. It has been shown that MRI T2* values in postmenopausal women assessed by QCT are moderately negatively correlated with BMD and have potential for assessing the severity of lumbar spine osteoporosis [73]. Many studies have confirmed the close association between T2* and osteoporosis, but there are differences in sensitivity, specificity, machine type, parameters, etc. [74]. Currently, there is no standard for diagnosing osteoporosis with T2*.
High-resolution magnetic resonance imaging (HR-MRI)
In recent years, HR-MRI scanning has been widely utilised in the field. This imaging technique precisely analyses the signal disparity between bone marrow and trabecular bone tissue. Within a high signal background, trabecular bone manifests as a distinct black network structure. Numerous studies have demonstrated a strong correlation between the bone structural parameters derived from HR-MRI and the morphological structural parameters of corresponding tissue sections. Moreover, HR-MRI scanning enables observation of trabecular bone microstructures at the micron level, facilitating accurate diagnosis of osteoporotic fractures [75–77]. While HR-MRI exhibits a high positive predictive value for detecting osteoporosis, it is worth noting that this examination method entails longer duration, higher cost, and relatively complex evaluation procedures. Therefore, further endeavours are required to enhance sensitivity, specificity, and accuracy levels and to standardise data processing.
Magnetic resonance spectroscopy (MRS)
MRS can evaluate the organic and inorganic components of bone and the density of the bone matrix. Currently, phosphorus spectroscopic imaging (13P-MRS) and hydrogen proton spectroscopy (1H-MRS) are used. Of these, 13P-MRS uses the echo signal of 13P in bone to determine the amounts of inorganic components of bone [78]. 1H-MRS uses chemical shifts to detect bone marrow water and adipose tissue, to analyse its biochemical composition and metabolic changes, and to indirectly assess bone mass at the molecular level [79]. MRS has not yet been widely used in the clinical evaluation of osteoporosis due to its demanding technique and many influencing factors.
Ultra-short echo time (UTE) imaging techniques
UTE is an imaging technique developed for short T2 tissues, which can directly visualise signals from short T2 tissues in the human body. Most of the T2 values of bone tissues are below 10 ms, and some are even less than 1 ms [80]. UTE pulse sequence can directly image bone cortex with spatial resolution, signal-to-noise ratio, and contrast-to-noise ratio correlated with the conventional pulse sequence. It clearly displays the morphology and structure of cortical bone and detects weak changes in porosity, with a sensitivity superior to that of micro-CT [81]. It can quantitatively analyse its composition, as well as quantitatively evaluating parameters such as phosphorus and sodium content, as well as analysing the distribution of cortical vasculature, metabolism of cortical blood vessels, and blood perfusion [82, 83].
Others
Diffusion-weighted imaging (DWI) reflects early changes in bone marrow components and can quantitatively evaluate bone marrow changes. The apparent diffusion coefficient (ADC) and signal-to- noise ratio (SIR) can better reflect vertebral bone density in patients with lumbar spine diseases and can be quantitatively evaluated for diagnosis of lumbar osteoporosis [84, 85]. Diffusion tensor imaging (DTI) characterises the direction of diffusion of water molecules and helps to assess fracture risk in osteoporosis patients [84]. Perfusion-weighted imaging (PWI) uses a paramagnetic contrast agent to induce transient changes in the local magnetic field of perivascular tissues, which can reflect changes in tissue microcirculatory perfusion and haemodynamics, and it can help to detect early abnormalities of blood supply in diseased tissues [86].
Conclusions
In conclusion, BMD remains the internationally recognised gold standard for diagnosing osteoporosis, while the aforementioned imaging techniques have their own specific applications (Tab. 1). DXA is widely employed for bone density assessment due to its cost-effectiveness, simplicity, and low radiation exposure. Moreover, it is endorsed by the WHO as the preferred method for diagnosing OP. VFA and TBS are used as extended tools of DXA.VFA mainly identifies asymptomatic vertebral fractures. Bone density assessment combined with VFA can not only detect previously unknown vertebral fractures but also improve the diagnostic rate for osteoporosis and severe osteoporosis. It has also been demonstrated that TBS is an effective method for predicting fracture risk independently, while the combination of BMD and TBS allows for the identification of patients at risk of fragility fractures at an early stage. The use of TBS is superior to BMD in the assessment of fragility fractures in patients with type 2 diabetes, and it offers significant advantages in evaluating and diagnosing secondary osteoporosis resulting from other causes. Although QCT is more accurate in measuring v BMD, it can measure the BMD of cortical and cancellous bone separately, but the radiation dose is relatively large. QUS is simple to operate, radiation-free, and is mainly used as a tool for osteoporosis screening. MRI can use tomography to understand the internal situation of the bone structure and indirectly evaluate the quality of the bone at the molecular level, but the examination is costly and time-consuming, and it is not used for clinical diagnosis or screening of osteoporosis at present. It can only be used as an important supplement to the assessment of osteoporotic fracture and differential diagnosis of osteoporosis. With the development of imaging technology, it provides technical support for further detection of bone microstructure, bone geometry, and bone strength, it and provides a theoretical basis for exploring bone physiology and the pathogenesis of metabolic bone diseases. In scientific research and clinical application, appropriate assessment tools need to be selected according to different needs, and the combined application of multiple methods can improve our scientific understanding of bone microstructure, identify high-risk groups more effectively, and reduce fracture risk to a greater extent.
|
Project |
Detection of parts |
Characteristic |
Function extension |
|
DXA |
Lumbar, hip, distal forearm, whole body |
The gold standard for the OP diagnosis and body composition analysis can be performed |
VFA TBS HSA |
|
QUS |
Calcaneus, radius, finger, tibia phalanges |
Economical, simple, and radiation-free, mainly used for OP screening |
Bone quality evaluation |
|
QCT |
lumbar vertebra, proximal femur, radius, tibia |
vBMD, can distinguish cortical and cancellous, used for OP diagnosis. More sensitive to fractures, especially micro-fractures, but has greater radiation |
HR-pQCT: provide bone morphology, microstructure, and biomechanical parameters Micro-CT: bone microstructure examination in vitro or animal specimens |
|
MRI |
lumbar vertebra, proximal femur, radius, tibia |
Bone microstructure imaging, the identification of fine fractures, new fractures and bone tumours. But the cost is higher, and the examination time is longer |
UTE: cortical imaging and quantitative analysis of bone components PWI: evaluate bone microcirculation MRS: bone quality evaluation |
Funding
We acknowledge the financial support from the Fundamental Research Program of Shanxi Province (20210302124570) and the Shanxi Provincial Health Commission’s “Four Batches” Science and Technology Medical Innovation Program (2021XM58).
Conflict of interest
The authors declare no competing interests.
Authors’ contributions
J.Y.L. and B.Y.S. mainly designed, wrote, revised, and finalised manuscript; M.L.H., C.Y.Y., and N.L. collected the literature and references. All authors have read and approved the manuscript.
