BONE-RESORPTION IN MULTIPLE-MYELOMA AND IN MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE - QUANTIFICATION BY URINARY PYRIDINIUM CROSS-LINKS OF COLLAGEN

To quantify osseous breakdown in multiple myeloma (MM), monoclonal gam mopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS , 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults, ion-paired, reverse-phase high-performance liquid chro matography (HPLC) was used to measure total urinary excretion of pyrid inoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of fr ee immunoreactive deoxypyridinoline (I-DPD) was determined with an enz yme immunoassay. MM patients had significantly (P <.0001) higher level s of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MC ;US, or patients with osteoporosis. The MGUS and osteoporosis groups p resented with elevated (P <.05) levels of urinary pyridinium cross-lin ks when compared with healthy controls. In 20 MM patients who subseque ntly received chemotherapy, the percent changes in I-DPD did not corre late with the changes in the monoclonal protein, In one of three patie nts experiencing a transition of initial MGUS into stage I MM, I DPD i ncreased above the upper limit of the normal range. In 13 patients wit h stable MGUS, I-DPD remained normal in repeated measurements, Based o n the upper limits of the normal range, the sensitivity of urinary pyr idinium cross-links in stage I and II MM was low (<50%), but it was be tween 78% (h-DPD) and 93% (I-DPD) in stage III MM. Specificity in pati ents with MGUS was between 87% (h-PYD) and 97% (h-DPC)). In conclusion , determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for eval uating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of I-DPD l evels may contribute importantly to clinical guidance, since increased I-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DP D levels did not change in parallel but instead diverged strongly afte r chemotherapy might explain the observation that bone lesions sometim es progress even in patients who achieve complete remission. (C) 1997 by The American Society of Hematology.