By John Barrat
Osteoarthritis in dogs is a serious and painful malady that effects many breeds. Recently Janine Brown, a biologist at the Smithsonian Conservation Biology Institute in Front Royal, Va., has been working with colleagues at Chiang Mai University in Thailand to evaluate the mineral composition of healthy dog pelvic bones and those showing severe osteoarthritis. The researchers found significant differences in a number of elements contained in healthy versus osteoarthritic bones.
The project was led by Dr. Korakot Nganvongpanit of the Faculty of Veterinary Medicine, Chiang Mai University, whose “studies use a relatively new approach to elemental analyses of organic samples, X-ray fluorescence (XRF), which was designed to determine the mineral content of inorganic materials, like rocks,” Brown says.
Here Smithsonian Science News asks Korakot and Brown a few questions about the recent paper that they and Kittisak Buddhachat, also of Chiang Mai University, published in the journal Biological Trace Element Research.
Q: What are the advantages of using X-ray fluorescence to study elements in bone?
Brown: XRF is quick, noninvasive—samples do not need to be destroyed or sub-sampled—and uses a portable, handheld unit to shoot an X-ray beam on a sample. It can detect multiple elements (in this study 10) at once in less than 5 minutes. Other studies might look at a few elements, but XRF allows for a more comprehensive assessment. Dr. Korakot has been using XRF to explore a multitude of questions using bones of all types—teeth, antler, horn and tusk—across some 15 different species.
Q: What led you to conceive of this study?
Korakot: The pathology of osteoarthritis is a major problem in many species and we want to understand the mechanism of this disease and differences in the various grades of osteoarthritis. Previous studies have focused attention on cartilage, but we are concerned that the bone beneath the cartilage (the subchondral bone) is also involved in the pathology of osteoarthritis. Many enzymes are involved in the osteoarthritis process, and elements are cofactors of these enzymes.
We also wanted to add to the general knowledge of the elemental composition of normal bone, as few studies look at the minor elements. Last, our XRF technique is able to detect multiple elements at once, allowing us to look not only at individual values, but how elemental proportions and ratios might be related to physiological function.
Q: You found much higher levels of iron and manganese in dog bones showing severe osteoarthritis. Why are these elements present in such high levels?
Korakot: Increasing concentrations of iron and manganese may be caused by subchondral bone sclerosis (thickening) and osteophyte (bone spur) formation with increasing collagen synthesis. Increased manganese in the severe osteoarthritis group might be associated with synthesis of new subchondral bone and osteophytes. Iron might be an important element involved in osteoarthritis in dogs and perhaps other species and therefore needs to be studied further.
Q: Is the dog’s body somehow being “tricked” into depositing these elements at higher levels or is it perhaps somehow trying to “heal” itself by increasing these elements in afflicted bone?
Korakot: We do not know for sure, but we can hypothesize that these elements are accumulated or needed for bone matrix synthesis, for modeling process of bone, and so it is possible the body is trying to compensate or increase metabolism to heal the tissue.
Q: Do high levels of iron and manganese exacerbate the malady?
Korakot: We cannot exactly answer this question either; however, we do believe that accumulation of these elements, perhaps as co-factors in enzymes, plays a role in matrix synthesis of the degraded areas. It may be how the body tries to remodel the bone of affected areas.
There is so much we do not know. Right now, we are identifying what minerals are different in relation to development of the disease. The next step is to determine why, and if there are any changes that can be made, perhaps dietarily, to mitigate osteoarthritis problems.
Q: Were you surprised to find calcium and magnesium percentages were not reduced even in bones representing severe cases of osteoarthritis?
Korakot: One of our hypotheses was that calcium and magnesium would be decreased in severe osteoarthritis because subchondral bone usually is weaker than normal bone and fractures more easily. But our results indicated the calcium/magnesium ratio was not different between different grades of osteoarthritis.
One possibility is that subchondral bone tries to repair itself and so the bone cells work to keep the calcium/magnesium ratio normal. We need to conduct more studies to find out why calcium and magnesium did not change in different osteoarthritis grades. It is perhaps related to the metabolism of bone minerals in cellular processes.
Q: How might this study someday help treat osteoarthritis in dogs and humans?
Korakot: It is very important to know which elements are involved in the path to osteoarthritis. Further studies are needed to find other elements important to help to prevent osteoarthritis or which are involved in the osteoarthritis pathway. For example, Zinc may be an important element to prevent or mitigate osteoarthritis.
Brown: We don’t know exactly what all this means yet but finding elemental differences in association with disease may be important to understanding causes and perhaps developing mitigating treatments for diseases of the bone and other mineralized tissues.