Biochemical markers of bone metabolism in multiple myeloma

Osteolytic bone disease is a major clinical feature of multiple myeloma (MM). Mechanisms of bone destruction are related to increased osteoclastic activity, which is not accompanied by a comparable increase in bone formation, as osteoblasts are functionally exhausted. Thus the lesions rarely heal and bone scans are often negative in myeloma patients with extensive lytic lesions, offering very little in the follow-up of bone disease. Biochemical markers of bone resorption, such as N- and C-terminal cross-linking telopeptide of type I collagen (NTX, CTX/ICTP, respectively), tartrate resistant acid phosphatase isoform-5b, bone formation (bone-specific alkaline phosphatase [BAP]), and osteocalcin provide useful information on bone dynamics. Several studies have shown that NTX, CTX, and ICTP are elevated in myeloma patients, reflect the extent of bone disease, and correlate with survival. Furthermore, they are useful in monitoring bone destruction during antimyeloma or bisphosphonate treatment. Markers of bone formation have produced conflicting results in trials. However, BAP correlates with bone pain, lytic lesions, and fractures in quite a few studies of MM. Novel markers, such as bone sialoprotein, receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin, osteopontin, dickkopf-1, and soluble Frizzle-related protein-2 have been found of value in assessing bone lytic disease in MM, but their promising results must be confirmed in large trials. In conclusion, although no marker provides optimal analysis of MM or of MM treatments, combinations of markers have at times helped in assessing MM stages and lytic bone disease and in monitoring specific treatment modalities. The need for further research in this field is clear.