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The New OSTEOCALCIN
Arthur Rosenthal, Ph.D
OSTEOCALCIN is a protein specifically produced by the osteoblasts, the cells which produce new bone tissue. The protein is utilized within the bone as an integral part of the process of its formation, but during this process a small amount of osteocalcin escapes into the general circulation. It is this osteocalcin in the blood which serves as a specific indicator that bone has recently been formed.
Osteocalcin in the blood is rapidly metabolized into one large fragment and some small fragments, which all in turn are then rapidly degraded to many smaller fragments of various sizes. In normal people, the intermediate-size fragments which are not immediately degraded to amino acids are readily excreted through the kidneys. In dialysis patients, however, these fragments are removed by the dialysis membrane only very slowly. If osteocalcin itself could be specifically measured at this point, its concentration would reflect bone formation in the period immediately preceding the measurement; but if a test for osteocalcin also measured these fragments, we could not tell whether the result reflected a very recent or a relatively old bone formation process.
In patients who have chronic renal failure and are on dialysis, it is important to have a good measurement of new bone production1 because this is an indicator of the effectiveness of the calcitrol which they are given or which they may still be producing. This hormone is normally produced in the kidneys and is therefore deficient in many or most dialysis patients.
There is a rather complex relationship between calcitriol, PTH, calcium, and phosphate, which, when the system is in good working order, regulates the balance between bone resorption and bone formation, processes that normally occur at a moderate rate. In the absence of sufficient calcitriol, however, and aggravated by several other deficits in dialysis patients, a process called renal osteodystrophy can begin, in which bone destruction greatly predominates over bone formation. This leads to severe osteoporosis, bone pain, fracturing, and ultimately invalidism and even death.
Unfortunately, up until now the methods for osteocalcin analysis were so non-specific that the great majority of results in dialysis patients were high above the normal range. They were thus uninterpretable in terms of indicating either recent or old bone formation. Only the few low values obtained could be fairly seen as representing minimal bone formation over a long period.
Very recently, however, a great improvement has been made by Nichols Diagnostics in the methodology for osteocalcin analysis, which is specific only for osteocalcin itself and its first (and largest} metabolic fragment. By using this method, most patient results are around the upper limit of normal, and are therefore quite interpretable as indicating recent bone formation. Low values thus indicate low or absent new bone formation. In addition, the new test is more environmentally friendly, since it does not use radioactive labels as does the earlier test Nonetheless the new methodology attains greater sensitivity because it uses a chemiluminescent label.
Thus, we now have a much more specific test to indicate the degree of success in attaining one of the major objectives of renal disease treatment, the prevention of renal osteodystrophy. Knowledge about the usefulness of this new analysis for osteocalcin should become widely known throughout the dialysis profession.
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