Periarticular bone predicts knee osteoarthritis progression: Data from the Osteoarthritis Initiative

https://doi.org/10.1016/j.semarthrit.2018.01.008Get rights and content

Abstract

Objective

Osteoarthritis (OA) is a disease with a substantial public health burden. Quantitative assessments of periarticular bone may be a biomarker capable of monitoring early disease progression. The purpose of this study was to evaluate whether measures of periarticular bone associate with longitudinal structural progression.

Methods

We conducted a 12–18 months longitudinal study using the Osteoarthritis Initiative (OAI). Participants received knee dual-energy x-ray absorptiometry (DXA), trabecular magnetic resonance (MR) imaging, and x-rays. Knee DXAs generated proximal tibial medial:lateral periarticular bone mineral density (paBMD) measures. Proximal tibial trabecular MR images were assessed for trabecular morphometry: apparent bone volume fraction (BVF), trabecular number, thickness, and spacing. Weight-bearing x-rays were assessed for medial tibiofemoral joint space narrowing (JSN). Chi-squared analyses assessed whether periarticular bone measures were predictive of worsening medial tibiofemoral JSN, adjusted for age, sex, and BMI.

Results

In all, 444 participants, mean age 64.2 ± 9.2 years, BMI 29.5 ± 4.6 kg/m2, and 52% male at baseline. Medial JSN (radiographic progression) occurred in 40 participants (9%). Higher baseline medial:lateral paBMD, apparent BVF, trabecular number and thickness, and lower baseline and decreased trabecular spacing were all associated with more progression of JSN in the medial compartment. From lowest to highest baseline medial:lateral paBMD quartile groups, 2%, 5%, 11%, and 18% had medial JSN progression, respectively, between the 36- and 48-month visits, p-values = 0.001 and 0.002 unadjusted and adjusted. The rate of change in medial:lateral paBMD, apparent BVF, and spacing were associated with more medial JSN. For rate of medial:lateral paBMD change from lowest to highest quartile, the proportion of each group that experienced medial JSN progression were 5%, 5%, 11%, and 18%, with an unadjusted and adjusted p-value of 0.005.

Conclusion

Baseline and most rates of periarticular bone change associate with knee OA structural progression, highlighting the close relationship between subchondral bone and JSN. Future studies should focus on developing these measures as predictive and pathophysiological biomarkers, and evaluating their deployment in clinical trials testing bone-targeted therapeutics.

Section snippets

Study design

This is a 12–18 months longitudinal observational cohort study of enrollees into the Osteoarthritis Initiative (OAI) Bone Ancillary Study with complete longitudinal follow-up of knee dual-energy x-ray absorptiometry (DXA), trabecular MR imaging, and knee X-rays read for radiographic medial joint space narrowing (JSN) scores.

Sample selection/setting

The OAI is a multi-center observational study of knee OA with a progression subcohort selected to have symptomatic radiographic knee OA [17]. The four OAI clinical sites

Results

In total, 629 participants were originally enrolled into the bone study. Of these, 144 had missing or insufficient quality trabecular morphometry MRIs, 34 had missing radiographs, 4 had missing DXAs, 1 had an artifact on DXA, 1 had knee arthroplasty by month 48, and 31 had a medial JSN score of 3 by the 36-month visit. This resulted in a final sample comprised 444 participants, among whom there was a slight predominance of men and Caucasian race (Table 1). Comparing those that were included and

Discussion

This study shows that cross-sectional and most longitudinal measures of periarticular bone, with a higher medial:lateral ratio, greater bone volume fracture, trabecular thickness and number, and lower trabecular spacing in knees of people with OA are associated with loss of medial tibiofemoral radiographic joint space. Interestingly, femoral neck BMD, a measure of systemic bone, both cross-sectionally and longitudinally are not associated with loss of medial tibiofemoral radiographic joint

Significance and innovation

  • This study shows that periarticular health in knees in people with OA associate with loss of radiographic joint space over a relatively short time frame.

  • The close participation of the periarticular bone with joint space loss in the pathogenesis of OA suggests that bone could be a target for therapeutic intervention.

Sources of funding

The ole of Bone in Knee Osteoarthritis Progression was sponsored by NIH/NIAMS (grant R01 AR054938). Periarticular Bone Density as a Biomarker for Early Knee OA was sponsored by NIH/NIAMS (grant R01 AR060718). Dr. Lo is supported by K23 AR062127, an NIH/NIAMS funded mentored award. This work was supported in part with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. The OAI is a

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    The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs or the National Institutes of Health.

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