While some previous research suggests that subchondral bone surfaces adapt their size in response to mechanical loading, other studies have suggested that joint morphology is highly canalized at the species level (articular contraint model – [29
]). We here used a malalignment model to address this question, as it has been established that the ratio of medial-to-lateral load magnitudes varies substantially between neutral, varus and valgus knees and the impact on medial-to-lateral bone surface areas can be investigated in the same knee. The results of our study suggest that subchondral bone size/geometry functionally adapts to the individual load pattern of malaligned knees and thus provides an indication that articular morphology may be subject of functional adaptation and phenotypic plasticity in bones of matured humans.
Strengths of the study include a) that malalignment was determined at baseline from full limb X-rays to determine the accurate mechanical axis (hip-knee-ankle angle) rather than from knee radiographs only, b) that subchondral bone surface area was reconstructed and quantified in 3D, using an MR sequence and image analysis process that has been thoroughly validated in the context of cartilage volume and thickness measurements and measurements of subchondral bone surface areas [6
]; c) that test-retest reproducibility errors of these measurements have previously been shown to be low [5
], and d) that adaptational processes of the bone were not only evaluated cross-sectionally but also longitudinally over an average two year observation period.
The study also has several limitations: a) Despite the relatively large number of participants, the sample size was relatively modest in view of the relatively small effect (increase in subchondral bone surface area with time) that was investigated; b) static knee alignment was measured, but not dynamic loading [32
]. It is known that static measurements predict about 50% of the variability in knee adduction moments [23
], and Thorp et al. [42
] found that static and dynamic measurements each explained the same proportion (18%) of the variability of proximal tibial bone mineral density in subjects with knee osteoarthritis; c) the technique used to ascertain femoral bone area based on coronal MR images may not fully capture the expansion occurring in AP direction; d) the study was limited to participants with established symptomatic and radiographic osteoarthritis, and therefore conclusions cannot be readily generalized to healthy joints. During the segmentation process, osteophytes were not included, in order to avoid the subchondral bone surface areas to be affected by osteophyte growth. A previous cross-sectional [26
] and a longitudinal study [44
] have described an increase in tibial bone area in osteoarthritic patients, the latter reporting relatively large increases (2.2±6.9% and 1.5±4.3% per annum in MT and LT, respectively). A later study by the same group [43
] reported an increase of tibial bone area also in healthy women (1.2% per annum in the medial and 0.8% in the lateral tibia), and, in a multi-centre study, we recently found a statistically significant increase of 0.3% of the tibial and femoral subchondral bone surface area over a period of 3 months [11
]. This increase did not differ significantly between healthy knees (n=97) and those with symptomatic knee osteoarthritis (n=61). An age-related expansion of bone cross sectional areas in the order of 0.18 to 0.60% per year has also been observed at other skeletal locations, such as the vertebrae, the femoral neck and the femoral shaft in a cohort of 1715 individual aged 67 to 93 years [40
]. Similar increases were seen at the distal radius and distal tibia in a cohort of 696 subjects aged 20 to 97 years [38
]. In view of these findings, we believe that the increase of subchondral bone surface area over time is not specific to knees with osteoarthritis [44
] and that osteophytes did not affect the measurement. However, we cannot exclude that uni-compartimental osteoarthritis had an effect on the medial-to-lateral ratio of subchondral bone surface area at baseline and on the ratio of the increase with time, through other mechanisms. To this end, a study in non-arthritic cohort would be necessary.
One prior study has looked at the relationship of alignment, cartilage volume, tibial (but not femoral) bone area, and chondral defects in a cohort of subjects consisting of 256 non-osteoarthritic and 56 arthritic knees [47
]. Alignment was determined from knee radiographs (not full limb films) and the tibial bone area from a single axially reconstructed slice of sagittal MRI scans. It is, however, somewhat unclear how the curved medial and lateral subchondral bone surface area can be accurately assessed from a single plane measurement, without including the intercondylar area. The authors reported the baseline lateral tibial bone area to be significantly higher in valgus (12.7cm2
) than in normal knees (12.0cm2
), but no significant differences were observed between varus and normal knees, or in the medial tibia. The change in medial tibial bone area was significantly lower (−0.2% per annum) in valgus knees than in normal (+0.6%) knees, but the authors concluded that overall there was no statistically significant association between varus/valgus alignment and change in tibial bone area (or cartilage volume loss/or progression of chondral defects). This negative finding persisted after stratifying for osteoarthritic and non-osteoarthritis subjects.
In contrast, we found a highly significant correlation of the medial-to-lateral ratio of the tibial subchondral bone surface area with hip-knee-angle angle and highly significant differences between varus, valgus and neutral knees. In the femur, the correlation was somewhat less strong, but still significant. The cartilage plates generally displayed an increase of the subchondral bone surface area over time, and in the femur the increase was significantly different between varus and valgus knees. These results are exciting, as they suggest that the size of the subchondral bone surface area adapts to mechanical loading, and that this adaptation may persist up to advanced age. Whereas from the perspective of bone fracture, adaptation by increased density provides increased structural strength of bones, adaptation of the subchondral bone surface area may be a more efficient mechanism of protecting the diarthrodial joint from undue stress. The increase in bone area may distribute the load over a wider area and thus reduces mechanical stress acting on the cartilage surface, whereas an increase in subchondral bone density (and stiffness) has no cartilage-protective effect. We have previously reported that the subchondral bone surface area is significantly higher in triathletes compared with physically inactive controls [15
] and is more highly correlated to body weight across between a wide range of species than cartilage thickness (Grams, Dissertation, LMU München, Germany). Taken together, these results suggest that knee joint morphology is not constained but phenotypically plastic, and that adaptation of subchondral bone surface area to mechanical loading may be a principle of functional adaptation of synovial joints. There are, obviously, limits to the effectiveness of this process: The size of the medial tibia in varus was 10% higher than in neutral knees, whereas the increase in load is likely much higher than that [1
]. Nevertheless, as malalignment may start with small offsets from the normal hip-knee-ankle angle and may become stronger once the cartilage and meniscus degenerate and the joint space narrows [22
], adaptation of subchondral bone surface area may provide initial protection and explain the relatively high number of varus and valgus knees that do not develop osteoarthritis [3
]. Once osteoarthritis develops, however, one has to take into account that while the subchondral area may still increase, this does not capture the curvature/congruity of the joint surfaces, and with focal remodelling and attrition the resulting contact area and mechanical stress may be negatively affected to still lead to a vicious circle of joint degeneration.
In conclusion, our findings suggest that tibiofemoral subchondral bone surface area functionally adapts to the medial-to-lateral load distribution in the knee. The longitudinal findings indicate that the ability of bone to modify its shape depending on mechanical loading may continue to take place at advanced age. This may be a general principle by which joints keep mechanical stress within the limits of cartilage tolerance.