Abnormal serum bone Gla protein levels in multiple myeloma. Crucial role of bone formation and prognostic implications.

The signification of serum bone Gla protein (serum BGP, osteocalcin) has been investigated in multiple myeloma. As a first step, quantitative iliac crest bone biopsies were performed in 19 patients; the serum BGP levels strongly correlated with histologic parameters of bone formation (r = 0.72-0.84, P less than 0.001) but not with those of bone resorption (r = 0.10). These results confirm that serum BGP is a marker of bone formation in multiple myeloma, as previously described in many other bone disorders. As a second step, serum BGP was measured in 117 patients with multiple myeloma as a systemic indicator of the degree of bone formation. Twenty-one percent of the patients had abnormal serum BGP levels (25 cases). The 14 patients with increased values (mean, 13.2 +/- 2.7 ng/ml) and thus increased bone formation belonged to a subgroup characterized by a lower osteolytic potential and a more indolent disease. On the other hand, the 11 patients with decreased values (mean, 1 +/- 0.3 ng/ml) and thus reduced bone formation had an advanced disease, extensive lytic bone lesions, a hypercalcemia frequently and a poor survival (mean, 4 months; range, 1-12). The biochemical investigations of the whole patient population, including serial studies in individual patients, have shown a large scatter of serum BGP levels, suggesting major differences in the bone formation rates. However, an overall inverse correlation was found between serum BGP and osteolytic potential. These results have confirmed the important role of the inhibition of bone formation in the occurrence of bone lesions in multiple myeloma and the interest of serum BGP to select a myeloma patient subgroup with low osteolytic potential and characterized by abnormally increased levels of this marker.