Osteoarthritis (OA) is one of the most common disorders in the elderly. It is estimated that by age 75 years, 85% of individuals show either clinical or radiologic evidence of OA (1). As OA of the hip progresses, changes in the shape of the femoral head develop, with flattened and irregular features becoming apparent. These changes can be observed on standard radiographs but are hard to quantify. The severity of OA is generally assessed using semiquantitative methods based on visual evaluation of a radiograph; for example, the Kellgren/Lawrence (K/L) scoring method (2) is used to assess a number of typical features of OA, including joint space narrowing (representing the loss of cartilage), development of osteophytes, presence of subchondral cysts, and subchondral sclerosis, on a 5-point scale. Quantitative measures of OA from medical images have previously focused on features of cartilage, whether indirectly by measurement of the joint space width on radiographs (3–6) or directly by measurement of cartilage thickness or volume from magnetic resonance imaging (MRI) scans (7–10). Investigations of the trabecular structure of bone have also been performed, again using either standard radiographs (11–13) or 3-dimensional MRI (14).
In addition to the deformation of bone and the growth of cysts and osteophytes, changes to OA bone include thickening of the subchondral bone plate, increased stiffness, increased bone mineral density and content, and alterations in the trabecular structure and size of the bone (13, 15–17). In OA, a proliferation of bone is observed, along with alterations in the material properties of the bone. Reduced mineralization of the bone has been observed in subjects with OA as compared with normal subjects and those with osteoporosis (18, 19). This occurs in conjunction with an increase in water content (18) and a reduction in the hardness or elastic modulus of the material as compared with that in the bone of subjects with osteoporosis (20, 21). Other differences in OA bone include an increase in metabolic activity (22) and an increase in both the amount and types of fat (23). This accumulation of evidence of changes occurring in OA bone at all levels has prompted the need for more detailed investigations of the bone, whole joint, and systemic factors in OA (24, 25).
Although gross morphologic features of the proximal femur have been rarely studied in patients with OA, geometric features have been identified as potential risk factors. The relationship between OA and morphologic changes is often attributed to abnormal loading patterns caused by unusual geometry. For example, the neck-shaft angle may lie outside the normal range (e.g., a varus or valgus hip) (26, 27), the femoral head could be uncovered or incongruent with the acetabulum as measured by the Wiberg center edge angle, or the morphologic appearance of the femoral head may be nonspherical (28–30). It is not known at which stage of the disease process these morphologic changes appear and how they might be related to disease progression.
Changes in the density and shape of the bone are traditionally believed to be a secondary effect of earlier cartilage degeneration. This leads to changed biomechanics and subsequent bone adaptation in late-stage OA. However, there is increasing recognition that the bone may be affected from the onset of the disease as part of a systemic process (24, 25), concurrent with or maybe even before cartilage degeneration has occurred. In this model, changes to bone become an important player in the etiology of OA, and thus more focus on the bone in the treatment of the disease is warranted. The proximal femur is a complex structure that cannot be fully described by 2 or 3 geometric measures alone. In this study we built a model of the shape of the femoral head and neck, i.e., the sites of the biggest shape changes that occur in OA, in order to investigate the relationship between morphologic features and radiographic OA.
The radiographic images in the present study came from the Rotterdam Study, a prospective cohort study involving men and women ages ≥55 years (31). To assess the development of OA, we selected subjects who had no radiologic signs of OA at baseline but then developed OA during the 6-year period before the followup visit. This allowed comparison of the shape of the femur in control subjects with that in OA subjects before, during, and after the development of radiographic disease. The method used for shape analysis in this study was the active shape model (ASM) (32, 33). This is a method for building a statistical model of shape variation on the basis of a data set of digital images.
The aim of the present study was to discover whether statistical analysis could be used to model the differences in gross morphologic features of the femoral head and neck between healthy subjects and subjects with hip OA as visualized on plain radiographs, and to model the changes in shape that occur in these subjects over time. This would allow quantification of the deformation of the femoral head, and also allow identification of characteristic morphologic features that may act as risk factors in the development of OA.
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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
The ASM is a method for building a statistical model of shape variation within a data set of digital images. It has been used for many purposes, from face recognition to medical imaging, including a number of musculoskeletal applications for investigating bone (37–39), prostheses (40), and cartilage (9, 41). In this study it was applied to build a statistical model of the proximal femur from standard pelvic radiographs as a way to observe the changes in the shape of the femoral head and neck attributable to OA over a 6-year period. We have shown that the ASM provides a comprehensive method of quantifying those changes in the radiographic images. It appears to represent a powerful tool for identifying those subjects at high risk of developing OA, as well as those who may require surgical intervention in the near future, as shown, in this case, by the need for THR within 6 years from a starting point of no apparent incident disease.
As expected, we were able to apply the model to chart the progression of OA over the 6-year study period, with the results revealing significant differences between the OA and control subjects at the end of the study. Of particular interest, however, the ASM also succeeded in identifying significant differences at baseline, at a time before the OA could be detected clinically using traditional methods (i.e., the K/L score), between those who went on to develop OA and the control group. In addition, these differences appear to be related to the subsequent severity of the disease, and therefore offer the possibility of early identification of those subjects who may be at higher risk of rapid disease progression. These changes could be separated from age-related changes and sex differences, and were solely related to the joint changes induced by the disease, as reflected in the K/L scores at the second time point.
As OA progresses, the femoral head becomes flattened and deformed. Although this process can be seen clearly on standard pelvic radiographs in severe cases, it is difficult to quantify. The shape of the proximal femur and its relationship to OA have been investigated in a number of studies, although the focus has been mostly on geometric properties such as the neck-shaft angle (varus or valgus femurs) (27), the femoral head height or diameter, or other measures (34, 42). The position of the femoral head in relation to the pelvis and acetabulum (the Wiberg CE angle) and the size and angle of the weight-bearing surface of the femoral head have also been investigated (28, 43). In this study we took a different approach and used the ASM to build a statistical model of shape variation across the whole of the femoral head and neck.
This model showed clear patterns of relationships between the subject groups and the modes of variation, with modes 1, 3, and 6 being identified as the key modes, which together accounted for 49.2% of the total variance in the data set (Table 2). The development of OA (measured by a change in the K/L score over time) resulted in a significant change in the mode 1 score (Table 2). This mode score reveals the way in which the femoral head flattens and deforms in combination with a shortening of the femoral neck as OA progresses (Figure 2A). There was no significant difference in this score between the OA and control groups at baseline, since there was a large biologic variation in the shape of the proximal femur, and relatively flat heads were not uncommon at baseline, even in members of the control group who did not go on to develop OA. Men, in particular, had a significantly lower mode 1 score than women at baseline, indicating a flatter femoral head among male subjects in the study. The change in mode 1 therefore appeared to reflect the progression of OA and its effect on the shape of the hip, but could not be used as a predictive measure or a marker for early OA.
Mode 6, in contrast, was significantly linked to OA in every comparison; not only did mode 6 scores significantly decrease over time in the OA group, in parallel with the increase in K/L scores, but also there were significant differences in the mode 6 score between the OA and control groups both at baseline (before OA was identifiable by the K/L score) and at followup. The range of shapes described by mode 6 is shown in Figure 2C. Subjects with lower mode 6 scores have a less pronounced curve from the upper femoral neck into the head, together with a sharper transition from the femoral head to the lower part of the neck, which, in this study, was associated with more severe OA. One of the most interesting observations about mode 6 was the significantly lower scores in the THR OA group than in the non-THR OA group, indicating that it may be possible to identify subjects at highest risk of requiring a THR at an earlier time point, even before OA is diagnosed. In general, a lower mode 6 score was associated with more severe OA or a worse prognosis (Figure 3).
Finally, mode 3 was also of great interest, because the score was significantly lower at baseline in subjects who required a THR during the course of the study, even though it was not significantly different between the OA (non-THR) and control groups at the end of the study, nor did it change in the OA (non-THR) group during the course of the study. This mode may be able to highlight individuals at an increased risk of THR in the near future, despite not being related to an increase in the K/L score. Similar to mode 6, subjects with low mode 3 scores have a sharp transition from the femoral head to the neck, but this is observed in the upper neck rather than the lower neck (Figure 2B).
In conclusion, the ASM can be used to measure and quantify the shape changes that occur in OA of the hip. Of particular interest, it can also identify individuals with a greater risk of requiring a THR in the near future and could detect differences between OA and control subjects at an earlier stage than is possible using current methods (the K/L scale). However, we would need to carry out more detailed investigations to determine whether these findings are representative of early OA or whether they indicate a predisposition to the disease. Mode 6 scores were significantly lower in the OA group than in the control group, both at baseline and at followup, and were lowest in individuals who went on to require a THR during the course of the study. This suggests that this mode of variation may be a marker not only of the development of OA, but also of its severity. The changes in shape observed with the development of OA (in modes 1 and 6) had high statistical power (>0.8) as well as significance, adding confidence to the likelihood of these results being replicated in a larger study. Although this model included effects of age and sex, we did not include other important parameters, such as body mass index or existing OA of the contralateral hip. Extension of the model to a larger segment of the femur or a combination with other measures would be likely to further improve diagnostic power.
The majority of research into OA still focuses on the cartilage. However, our data show that bone-related parameters deserve more attention, even in the early and preclinical stages of OA. The ASM provides a new way to measure the shape of the bone in OA, and provides markers that relate to the progression and prognosis of the disease. In combination with other measures of cartilage (5, 6, 8, 9), bone density and volume (27, 31, 43–46), and trabecular structure (11, 12, 14), the ASM may represent a powerful tool for improved measuring, monitoring, and understanding of OA.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Dr. Gregory had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study design. Gregory, Day, Pols, Weinans, Aspden.
Acquisition of data. Gregory, Waarsing, Day, Pols, Reijman, Weinans.
Analysis and interpretation of data. Gregory, Day, Weinans, Aspden.
Manuscript preparation. Gregory, Waarsing, Day, Pols, Reijman, Weinans, Aspden.
Statistical analysis. Gregory, Waarsing, Day, Aspden.