Serum C-Terminal Telopeptide Maintains Its Correlation with Bone Disease in Myeloma Patients Even Under Treatment with Bisphosphonates

Abstract 4003

Skeletal related events (SREs) are a significant cause of morbidity and mortality in multiple myeloma (MM). Markers of bone turn-over, in particular serum C-terminal telopeptide of type I collagen (CTX), can be used for monitoring early signs of bone damage either in osteoporosis or in neoplasm such as Multiple Myeloma. Since serum CTX levels are significantly decreased during bisphosphonate treatments (Dennis, N Engl J Med 2008), it is not clear whether serum CTX monitoring still retain a role in predicting SREs once bisphosphonate treatments was started. Aim of this study was to test whether serum CTX monitoring significantly correlates with active bone disease in a population of MM patients irrespective of concomitant bisphosphonate treatment.

An unselected cohort of 87 patients with multiple myeloma diagnosed at our Hematology Division with the following characteristics entered this study: the availability of a baseline determination of serum CTX prior to start bisphosphonate therapy, multiple sequential serum CTX determinations (≥2 performed with an interval of at least 4 weeks), a radiologic evaluation available at the time of any SREs. The study was approved by our local ethical committee and conducted according to Helsinki Declaration guidelines. Patients baseline characteristics were the following: M/F 59%/41%, median age 60 (range 37–86), Durie and Salmon stage I/II/III (11%/14%/75%). During the study period (median follow-up 2.8 year, range 0.4–21 years), 73 patients (83%) experienced at least one SRE. Development of SRE was evaluated by standard skeletal x-ray, CT or MRI scan. Serum CTX was measured by an enzyme chemiluminescence method. A total of 260 serum CTX determinations were available for statistical analysis (median number of determinations for each patient 3, range 2–9). Univariate analysis found a statistically significant association between serum CTX and bone disease status with higher values in patients with active lytic lesions when compared to patients without radiological evidence of bone disease (median value 0.411 vs 0.356, p<0.001). By contrast, we observed significantly lower serum CTX values in patients under bisphosphonates treatment (median value 0.160 vs 0.355, p=<0.001). Association between serum CTX values, bone disease status and active bisphosphonates treatment was analyzed with a time-series linear model, accounting for measurement being repeated sequentially on each patient (random-effects GLS regression). Bone disease status and bisphosphonates treatment resulted significantly and independently associated to serum CTX (regression coefficient 0.222, 95%CI: 0.107–0.338, p<0.001 and 0.208 95%,CI: 0.320–0.096, p<0.001 respectively for bone disease status and bisphosphonates, cfr Tab 1). In addition, variations of CTX serum levels correlated significantly with the presence of active bone disease even under treatment with bisphosphonates (p<0.001).

In conclusion, this study confirmed a positive association between serum CTX and presence of active bone disease. In addition serum CTX levels show a significant decrease under treatment with bisphosphonates. Taking into account these observations, patient-specific variations rather than the absolute serum CTX value should be used for detecting the onset of new SREs during a concomitant bysphosphonates treatment.

Tab 1: Levels of serum CTX according to bone disease status and bisphosphonates treatment.