BACKGROUND: Biochemical markers of bone metabolism are useful indicators of bone turnover in pts with malignant bone disease. Elevated N-telopeptide (NTX) levels were correlated with increased risks of skeletal-related events (SREs), disease progression, and death in pts with primary bone lesions from MM (Coleman RE, et al. J Clin Oncol. 2005). The prognostic value of other markers (eg, pyridinoline [PYD] and deoxypyridinoline [DXP]) in pts with MM is unknown.
METHODS: This study investigated the association between NTX, PYD, DXP, and bone alkaline phosphatase (BAP) levels and risk of SRE or pathologic fracture in pts with MM who were treated with 4 mg zoledronic acid in a phase III clinical trial (Rosen LS, et al. Cancer J. 2001). Cut-off values for low, moderate, and high marker levels were based on prior reports and the investigators’ experience with bone marker data. Both univariate and multivariate analyses were performed and risk ratios were derived for pts with elevated levels of each bone marker relative to pts with low marker levels.
RESULTS: By univariate analysis, moderate (50 to 100 nmol/mmol creatinine) and high (> 100 nmol/mmol creatinine) NTX levels corresponded with significantly increased risks of any SRE, onset of first SRE, or pathologic fracture. Elevated levels of PYD corresponded with a significantly increased risk of SREs, the onset of SREs, and pathologic fracture. Although there were some significant correlations, the association between DXP and BAP levels and risk of skeletal morbidity was inconsistent (Table). In multivariate models, only NTX and DXP were significant, and NTX had a stronger effect.
Risk Ratios By Univariate Analysis for SRE Compared With the Respective SRE Pathologic fracture Any Onset (1st) Any Onset (1st) NTX ≤ (vs 50 nmol/mmol creatinine) > 50 – 100 2.26 (.003) 2.76 (.012) 2.98 (< .001) 3.78 (.001) > 100 4.01 (.001) 6.80 (< .001) 5.35 (< .001) 8.87 (< .001) DXP ≤ (vs 15 nmol/mmol creatinine) > 15 – 30 1.95 (.016) 2.14 (.015) 2.30 (< .001) 2.29 (.009) > 30 1.89 (.041) 3.58 (.006) 1.74 (.134) 2.88 (.046) PYD ≤ (vs 62 nmol/mmol creatinine) > 62 1.89 (.009) 2.06 (.006) 1.74 (.028) 1.97 (.017) BAP ≤ (vs 146 U/L) > 146 1.48 (.103) 1.89 (.042) 1.69 (.042) 1.86 (.063)
CONCLUSIONS: Elevated baseline PYD, DXP, and BAP levels are significant predictors of an increased risk of some SREs and may therefore have clinical value. Elevated NTX levels are a consistent significant predictor of an increased risk of SREs and pathologic fractures. NTX levels may therefore aid in identifying patients at risk for skeletal complications.