Advances in osteoporosis imaging
Introduction
Osteoporosis is the most common metabolic bone disorder. It is defined as “a skeletal disease, characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture” [1]. As a disease of the elderly, the prevalence will increase as the population ages. Currently every third post-menopausal woman and every fifth man older than 50 years, suffer from osteoporosis [2]. The fractures compromise life quality and shorten life expectancy [3], [4]. Treatment costs in Europe are expected to increase up to 75 billion Euros by 2050 [5]. As preventive therapies are available, the assessment of osteoporosis must be intensified and optimized and diagnostic techniques characterizing bone tissue beyond bone mass/density need to be developed [6], [7].
Bone is a highly metabolic tissue, incorporating multiple functions such as stabilization of the body, protection of the inner organs and calcium storage. It is a composite, mainly consisting of type I collagen (40%), hydroxyapatite (45%) and water (15%). On a structural level, cortical bone can be distinguished from trabecular bone. Trabecular bone is a combination of rods and plates within a cortex of variable thickness. Single trabeculae have a thickness of 50–200 μm, and bone marrow fills the 200–1000 μm wide interspaces [8]. Bone constantly models and remodels; in young individuals, bone formation exceeds bone resorption, up to the time that peak bone mass (PBM) is reached around the age of 30–35 years. According to Wolff's law, this remodeling process is adapted to the mechanical loading placed on the skeleton [9]. However, hormones also influence this process: in the elderly, with decreasing levels of oestrogen and testosterone, bone resorption exceeds bone formation; bone mass in an individual adult is determined by peak bone mass, and rate and amount of bone loss [10].
Bone mass, or bone mineral density (BMDa; g/cm2), as measured by photon absorptiometry is the traditionally used parameter to diagnose osteoporosis [11]. BMD was the first parameter to quantify bone properties non-invasively, correlates with bone strength and predicts fracture risk of a patient to some extent [12]. However, half of the post-menopausal women with incident, low energy fractures have a BMD above the World Health Organization (WHO) threshold definition of osteoporosis (T score at, or below, −2.5) [13], as BMD does not reflect bone quality, the second main feature affecting bone strength and fracture risk [14]. Bone quality refers to trabecular bone architecture, damage accumulation (e.g., micro fractures), cortical bone thickness and geometry, turnover, osteon and osteocyte density and other factors such as cell viability [6]. Among these, bone geometry, in addition to trabecular and cortical micro-architecture, are the most accessible with non-invasive imaging techniques. Many studies have shown that both cortical and trabecular architecture give information additional to BMD in assessing bone strength and discriminating between healthy (non-fracture) and osteoporotic patients [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. Effects of therapeutic agents are greater in trabecular architecture compared to BMD [67], [70], [71]. Assessment of trabecular structure also improves knowledge of the patho-physiology of osteoporosis and shows the type of architectural changes, i.e. the transformation from plate-like to rod-like trabeculae and the accumulation of micro-damage [8], [25], [26], [27]. Recently, MR based measures of bone marrow function and composition, such as spectroscopy and perfusion, have also been introduced to study bone metabolism [28], [29], [30].
Additionally, it is important to note that other radiological methods can improve the diagnosis of patients with osteoporosis, apart from the measurement of BMD. Lateral chest radiographs and CT (sagittal reformations from 3D volume MDCT) are performed in many elderly patients and can be used to identify vertebral fractures [31], [32], [33]. An estimate of BMD can also be obtained from contrast-enhanced CT scans [34], [35].
Section snippets
High resolution imaging of trabecular bone
To analyze trabecular bone architecture, high resolution imaging is mandatory. As tomographic imaging techniques evolve, in-vivo 3D imaging of trabecular bone is becoming more feasible. Several imaging techniques have been used at various skeletal sites for analysis of the cortical and trabecular bone architecture.
Assessment of cortical bone
Osteoporotic bone loss involves both trabecular and cortical bone. While changes of trabecular bone occur earlier than alterations of cortical bone, and thus might be more sensitive for an early diagnosis of osteoporosis, cortical bone geometry, thickness and porosity are important predictors for hip fractures [97], [98], [99], [100].
Previous studies focused on cortical bone imaging to study predominantly geometric parameters [24], [101], [102], [103]. Several groups found that thin cortical
Imaging of the bone marrow function
Recently dynamic contrast-enhanced MR imaging, MR diffusion imaging and MR spectroscopy have been proposed to study bone marrow composition and function, as increase in bone marrow fat has been associated with osteoporosis and increased fracture risk [28], [29], [30]. Griffith et al. found in 110 post-menopausal subjects that a decrease in vertebral marrow maximum enhancement and enhancement slope, and an increase in marrow fat content measured with spectroscopy were associated with lower BMD
Osteoporosis assessment with imaging studies performed for other purposes
Chest radiographs are among the most frequently performed studies in elderly patients [107]. Several studies have shown that vertebral fractures can be present on lateral chest radiographs enabling the diagnosis of osteoporosis to be made. However, there is evidence that such fractures are under-reported, so it is essential that radiologists are aware of how important it is to the diagnosis and management of patients with osteoporosis that such fractures be clearly and accurately reported [31],
Clinical application
Many studies, some of them cited above, give strong evidence that fracture risk is independently determined by BMD and bone architecture. Thus fracture risk is best assessed by both bone mass and structure. However, taking into account costs and availability, one would perhaps favour a stepwise approach for diagnosis in an individual patient: Beginning with a clinical assessment of risk factors (WHO FRAX™ http://www.shef.ac.uk/FRAX/), patients could be separated into low-risk, an uncertain risk
Conclusion and future developments
The analysis of bone structure, in addition to bone mass, is an exciting and developing field in the diagnosis of osteoporotic bone. With the recent technical developments in MR, including the availability of clinical 3 T scanners, and advances in CT, including the introduction of clinical Micro-CT, imaging of true trabecular bone architecture is becoming more feasible. In-vitro studies show that trabecular architecture can be depicted with these tomographic techniques and bone strength
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