Love is stronger than hate: a story of two contrast agents

The ability to image cartilage is important for diagnosis and analysis of a joint during arthritis. Normal X-rays cannot “see” cartilage because it can’t refract the X-rays like bone tissue can. In other words, it’s invisible. Until recently.

Scientists decided to take advantage of the fact that cartilage tissue is negatively charged (anionic, in science terms), due to the abundance of glycosaminoglycans (read: carbohydrate and sugar molecules) that help keep the tissue hydrated and bouncy to protect your bones. The dyes they invented, however, function based on repulsion. They work on the principle that anionic dyes will not go into highly anionic tissue, so a lack of dye equals healthier cartilage tissue.

This research decided to examine whether positively-charged dyes worked better, worse, or about the same as their anionic counterparts. Their hypothesis was that the attraction forces between negative and positive charges would create better dye interactions, and therefore better imaging, in cartilage tissue. To do this experiment, they took explants – round “plugs” – of bovine cartilage tissue and soaked them in both anionic (2 types) and cationic (1 type) dyes. They were able to evaluate all three dyes on each explant because the dye will naturally diffuse out of the tissue over time. Between each dye, the explants were allowed 24 hours of “wash-out” time to remove the dye, and were imaged to confirm that the dye was undetectable compared to the baseline measurements for each sample.

They imaged these cartilage tissues using a microCT machine – a kind of glorified X-ray device - that can detect these dyes, and analyzed the resulting images.

As predicted, they found that the positively-charged dye gave them better contrast between cartilage and non-cartilage tissue. Even better, though, the cationic dye accurately reflected the natural tissue distribution of GAGs within each cartilage plug, while neither anionic dye was able to recapitulate that structure.

This finding is good news for studying and tracking cartilage health in people with osteoarthritis. Claims by the authors that this discovery could also lead to new therapies might be a far stretch, but if they come up with a good therapeutic idea, I’ll take it.

Article Cited:
Bansal, PN et al. “Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage”. OA & C. Vol. 19, Issue 8, pp. 970-976.

Knee bracing does not improve osteoarthritis symptoms

People suffering from knee osteoarthritis (OA) are likely to have pain in the patellofemoral joint (PF) that stems from possible patellar malalignment. In fact, 65% of all knee OA cases involve the PF. Taping the patella helps alleviate this PF pain, but repeated use of tape can irritate the skin and is hard for older adults to apply on their own. This research sought to answer the question of whether a knee brace with a patellar stabilizing strap could give similar pain-relieving results as taping to avoid the limitations of PF taping.

Sadly, this particular model of knee brace was unable to make any difference for the 67 people in this trial over the course of 6 weeks. The control brace, which was the same as the treatment brace but with the patellar stabilizing strap removed, had exactly the same effect as the “active” brace.

That being said, the positive effect of taping may be recapitulated in a different knee brace since each model is constructed differently. The caveat for taping is that the definitive taping studies used younger patients with general knee joint pain, rather than specific PF osteoarthritis cohorts. The authors argue that this narrower patient population would have given them a better chance at seeing clinically relevant differences in this bracing study. However, they conclude from their data that knee bracing for older patients with non-traumatic knee OA may not be effective at reducing pain, and the challenge of finding a non-pharmaceutical intervention for knee osteoarthritis remains.

Article Cited:
Hunter, DJ et al. “A randomized trial of patellofemoral bracing for treatment of patellofemoral osteoarthritis”. OA & C Vol. 19, Issue 7, pp792-800.

Can weight loss improve osteoarthritis in obese patients?

There is an obvious correlation between how much you weigh and the resulting impact on your knees. The heavier you are, the more likely you are to have joint pain and arthritis. In this study a group of 157 obese patients (82% female, 18% male) received dietary counseling over 16 weeks in order to reduce their overall weight and to thereby study how knee joint loading changes due to weight loss.

The group lost 13.2% of their original body mass (approximately 13.7 kg, or 30 lbs), on average, and reduced their BMI by 13.8%. The peak compressive loads in the knee stayed the same, at about 2-4 times body weight. However, a few important measures of the mechanics of knee loading changed in a positive direction. The peak knee joint load was reduced by 2.2 kg for every 1 kg of weight lost and the knee abductor moment (KAM) saw a 12% decrease, which indicated a decrease in the total medial joint loading. The medial compartment (or internal part of the knee joint) is more commonly affected by osteoarthritis than its lateral counterpart, so reducing the absolute amount of weight-based load in this medial area bodes well for reducing knee osteoarthritis in overweight patients.

The best clinical result, though, was a 30% in reported joint pain after weight loss, which was further confirmed by a 4% increase in the self-selected walking speed, since patients will move more when they are in less pain. Researchers had to compensate for this increased walking speed in order to see the effects of weight loss on joint loading because higher walking speeds increase the loading of the knee joint.

Overall, the weight loss program had significant benefits to obese patients suffering from osteoarthritis of the knee. By reducing the total weight of their bodies, they improved their knee loading mechanics and pain scores. Losing 5.1 kg (11.2 lbs) and maintaining that loss can reduce the risk of developing OA by 50%. Now that is good reason to choose grilled chicken over a Big Mac.

Article Citation:
Aaboe, J. et al. “Effects of an intensive weight loss program on knee joint loading in obese adults with knee osteoarthritis”. Osteoarthritis & Cartilage Vol. 19, Issue 7, pp. 822-828.

Eat your fish: Omega-3s improve osteoarthritis in guinea pigs

What if reducing your risk of osteoarthritis was as simple as changing your diet? According to new research from the journal Osteoarthritis & Cartilage, it might just be that easy.

Knott and colleagues studied the effect of omega-3 fatty acids on the progression of osteoarthritis in a naturally-occurring OA model, the Dunkin-Hartley (DH) guinea pig. These animals are genetically predisposed to develop OA as they age, so starting at age 10 weeks the guinea pigs were given a diet that either contained average American-diet levels of omega-3 fatty acids or had a high-omega-3 diet (fish oil supplement). A non-OA-prone guinea pig strain was used as the control group in order to rule out any general physiological changes in the guinea pigs due to this diet.

By adding high levels of omega-3s to the guinea pigs’ diet, the researchers were able to reduce the visual signs of OA by 50% (histological scores). They saw statistically significant reductions in the destruction of cartilage as determined by semi-quantitative scoring (OARSI standards), toluidine blue staining for a critical component of healthy cartilage, glycosaminoglycans (GAGs), and overall cartilage structure.

This diet change did not completely eliminate all risk factors. Collagen II, an important component of cartilage, still had significant mineralizing-prone modifications in the DH guinea pigs, while the non-arthritic guinea pigs showed only low levels of this collagen modification. However, out of 20 risk factors examined in the omega-3 diet DH pigs, 16 showed either significant differences or positive trends toward the levels seen in the arthritic-resistant pigs. Only two factors showed no significant changes, and the remaining two had non-significant trends in the opposite direction.

These results suggest that people with inherited risk of OA may be able to mitigate the onset and severity of the disease by changing what they eat. This diet-based approach to treating arthritis may be a significant tool in a holistic approach to this chronic disease.

Article citation:
Knott, L. et al. “Regulation of OA by omega-3 polyunsaturated fatty acids in a naturally occurring model of disease”. Osteoarthritis & Cartilage, In Press 2011.