Multiple myeloma: Changes in serum C-terminal telopeptide of collagen type I and bone-specific alkaline phosphatase can be used in daily practice to detect imminent osteolysis

Abstract Objective: Monitoring of bone disease in multiple myeloma is becoming increasingly important since bone protecting treatment with bisphosphonate is becoming restricted after the awareness of osteonecrosis of the jaw. Despite the potential of biochemical markers of bone remodeling to monitor dynamic bone turnover they are not used in everyday practice. Here we investigate their usefulness to detect imminent progressive osteolysis in relapsing patients with multiple myeloma. Methods: In an unselected cohort of 93 patients we measured the bone resorption markers C-terminal telopeptide of collagen type-I (CTX-I), C-terminal crosslinked telopeptide of type-I collagen generated by MMPs (ICTP), N-terminal crosslinked telopeptide of type-I collagen (NTX-I), and the bone formation marker bone-specific alkaline phosphatase (bALP) monthly for two years. Retrospectively, we identified 40 cases where patients had progressive disease. We investigated how the bone markers developed prior to disease progression. Results: We observed that CTX-I and bALP changed significantly before progressive disease was recognized. More interestingly, these changes differed depending on whether concurrent progressive osteolysis was present. In patients with progressive osteolysis there was a large increase in bone resorption which was not compensated by increased bone formation. In contrasts, patients with stable bone disease had only a slight increase in bone resorption which was compensated by concurrent increased bone formation. By calculating a patient specific CTX-I/bALP ratio we quantified the risk a patients experiences if the ratio increases. Conclusion: By analyzing patient specific changes in the ratio of CTX-I/bALP we might tailor treatment with bone protecting agents in the individual patient.