Calcification of human articular knee cartilage is primarily an effect of aging rather than osteoarthritis

Abstract

Objective: Pathologic calcification of articular cartilage in human knees is often associated with advanced age and conditions of osteoarthritis (OA). Coincidently, most studies that have characterized calcification in joint cartilage have examined populations that are aged and presenting with clinical symptoms. Generally, these studies rely upon relatively insensitive plain radiographs or synovial fluid crystal analyses to quantify calcium levels. The purpose of this study was to examine the relationship between cartilage calcification and aging in an unselected donor population of diverse age using highly sensitive calcification imaging.

Methods: A group of 106 knee blocks were obtained from 56 individual donors (25 females and 31 males, aged 12-74, avg. 50.3 years). Condylar surfaces were graded on a 4-point OA grading scale for cartilage degeneration. The condyles were cut into approximately 7-10mm thick slabs. Using a Faxitron radiography system, high-resolution images were taken of the slabs to specifically image calcification in cartilage. The quantified calcification areas were then analyzed and correlations with both OA grade and age were assessed.

Results: Every knee presented some measurable calcification. The relative calcium deposition had a significant positive correlation with age. This same positive correlation was seen between condyles showing grade 1 and 2 changes. OA grades higher than 2 did not present any further significant increase in calcium levels.

Conclusion: These observations indicate that age rather than OA is the predominant factor driving progressive pathologic calcification in articular cartilage.

Figure 1

Study population histogram by decade. n=56.

Figure 2

Gross femoral and tibial condyles indicating areas of condylar strips and the resulting slabs used for analysis. The cartilage of the slabs was trimmed to remove any bone fragments introduced during harvest.

Figure 3

Radiographic images of (A) a non-calcified lateral tibial cartilage and (B) a highly calcified region of a medial tibial plateau indicated by arrows. Analysis of these calcified areas is illustrated in (C), measurements (in red) of the calcium deposition area by thresholding and manual methods, and (D), the total measured cartilage area. The % calcification is derived from these two areas (9.6%).

Figure 4

Cartilage surface grade versus age in years. Significant positive correlations were observed for both the (A) tibial and (B) femoral surfaces with increasing age. A tied P value by the Kruskal-Wallis test was less than 0.001 for both groups. Median values are shown. Shaded bars represent 25% and 75% and error bars represent 5% and 95% confidence intervals. *p<0.01 by the Scheffe’s post hoc test.

Figure 5

Scatter-grams of tibial and femoral specimens related with age and percentage with cartilage calcification. Significant positive correlations were observed for all sections. The following values were observed for the tied P value by Spearman’s correlation coefficient by rank test: (A) Lateral tibial plateau, P<0.001 with r_s =0.346, (B) Medial tibial plateau, P<0.001 with r_s=0.338, (C) Lateral femoral condyle, P<0.001 with r_s =0.615, and (D) Medial femoral condyle, P<0.001 with r_s=0.627.

Figure 6

Percentage of cartilage calcification area for all condyles grouped by age and representative radiographic images illustrating the calcification. Asterisks indicate a significantly greater calcified percentage compared to the younger age group. Arrows indicate calcified regions. *p < 0.05 by the Scheffe’s F post-hoc test.

Figure 7

Percentage of cartilage calcification area for all condyles grouped by cartilage grade. Asterisks indicate a significantly greater calcified percentage compared to the lower grade group. *p < 0.05

Figure 8

The comparison between percentage of cartilage calcification area and age for non-osteoarthritic grades 1 & 2. (A) In minimally fibrillated condyles (grades 1 and 2), calcification is seen to increase as a function of age. (B) This pattern is also seen in the presence of more sever fibrillation (grades 3 and 4). *p<0.05.