Osteoarthritis Knee Pain Connected to BMD

Low proximal tibial trabecular bone mineral density (BMD) may play a role in the development of osteoarthritis-related knee pain, a new study suggests.

Knee osteoarthritis is characterized by changes in cartilage and subchondral bone and pain is often the primary sign that a patient may have osteoarthritis, the researchers noted, but the exact origin of pain within the knee joint is poorly understood because the pain could be related to many structural factors, such as altered joint alignment, bone marrow lesions, and cysts.

To date, research investigating the association between osteoarthritis-related knee pain and bone has focused primarily on bone near the subchondral surface, and there have been no specific studies reporting the relationship between epiphyseal or metaphyseal trabecular BMD and pain.

Led by Wadena D. Burnett of the University of Saskatchewan in Canada, researchers writing in Arthritis Research & Therapy set out to examine the relationships between proximal tibial trabecular (epiphyseal and metaphyseal) BMD and osteoarthritis-related pain in patients with severe knee osteoarthritis.

The study

The study included 42 participants with osteoarthritis, recruited before total knee replacement surgery. Osteoarthritis severity was classified using Kellgren-Lawrence scoring, and pain severity was measured at the affected knee joint using the pain subsection of the Western Ontario McMasters Osteoarthritis Index (WOMAC). The researchers also used the Self-Administered Comorbidity Questionnaire to assess participants for any potential confounding comorbidities, such as diabetes and heart disease.

The researchers used 3-dimensional image processing techniques and a custom algorithm developed specifically for this study. Repeatability of the algorithm was assessed on an independent sample of healthy participants and participants with osteoarthritis using recommended methods.

The novelty of this study was focusing the analysis in the epiphyseal and metaphyseal trabecular regions, which are largely void of cysts, to determine any potential independent associations between BMD and pain.

The findings

“Our regression models suggested that tibial epiphyseal and metaphyseal BMD independently explained variance in total pain in patients with osteoarthritis prior to [total knee replacement],” the researchers concluded. “Patients with lower BMD tended to have higher levels of pain.”

Models indicated that medial epiphyseal BMD was also a significant predictor of total osteoarthritis-related pain, again with lower BMD associated with higher levels of pain. In addition, the study reported a significant association between age and pain assessed by WOMAC, whereby older patients reported lower pain. Specifically, younger male patients reported higher WOMAC pain scores, though the researchers recommend further analysis to determine whether this finding is unique to this sample or more widespread. No associations were found between age and BMD.

Implications

The study has a few limitations. First, pain severity was based on the entire knee joint, so it is uncertain whether the pain originated within the proximal tibial bony structure, other tissues, or a combination. Second, all participants were in the late stages of osteoarthritis, so applying these findings to patients in the early stages may not be possible. Third, the sample size was small. Further analysis with larger samples that include healthy participants and participants with various stages of osteoarthritis severity and pain are needed to verify these preliminary findings.

In addition, whether low BMD is the result of trabecular thinning or wide trabecular spacing is unclear, so investigating the links between pain and trabecular microarchitecture with advanced texture analysis and smaller voxel sizes would be advantageous.

Rational therapeutic targeting requires a clear understanding of which structures contribute to pain. These findings suggest there may be overlooked characteristics in proximal tibial BMD that play a role in the pathogenesis of osteoarthritis-related knee pain. However, this study presents statistically significant relationships as opposed to clinically significant relationships, so considering the clinical effect that changes in epiphyseal or metaphyseal BMD may have on osteoarthritis-related knee pain is important.

A rational therapeutic approach would be to monitor bone while simultaneously striving to maintain bone and limit bone loss, monitoring density changes in these regions. These preliminary findings may also be clinically important for total knee replacement preparation and planning, because patients with low preoperative BMD have been shown to be at higher risk for implant failure by loosening or migration, revision surgery, and failure after revision procedures.

References:

Burnett WD, Kontulainen SA, McLennan CE, et al. “Proximal tibial trabecular bone mineral density is related to pain in patients with osteoarthritis.” Arthritis Res Ther. 2017;19:200. doi: 10.1186/s13075-017-1415-1419.