Abstract

BACKGROUND: Biochemical markers of bone metabolism provide valuable information about rates of bone turnover in patients with malignant bone disease. N-telopeptide of type I collagen (NTX) is released during osteolysis and is indicative of pathologic increases in bone resorption. Elevated NTX levels recently have been correlated with increased risks of skeletal-related events (SREs, defined as pathologic fracture, surgery to bone, spinal cord compression, hypercalcemia of malignancy, and the requirement for palliative radiotherapy), disease progression, and death in patients with bone metastases from solid tumors (

Coleman RE, et al.
J Clin Oncol.
2005
;
23
:
4925
–4935
;
Brown J, et al.
J Natl Cancer Inst
.
2005
;
97
:
59
–69
).

METHODS: The current univariate analysis investigated the correlation between NTX levels at baseline and SREs (including palliative radiotherapy to bone) in patients with multiple myeloma who were treated with 4 mg zoledronic acid in a phase III clinical trial (

Rosen LS, et al.
Cancer J.
2001
;
7
:
377
–387
).

RESULTS: Forty-three patients had low NTX (< 50 nmol/mmol creatinine), 45 had moderate NTX (50 to < 100 nmol/mmol creatinine), and 18 had high NTX (≥ 100 nmol/mmol creatinine) at baseline. Patients with either moderate or high NTX at baseline had significantly increased risks of on-study SREs and significantly increased risks of experiencing their first SRE while on-study compared with patients with low NTX (Table). A similar correlation was also observed for pathologic fractures alone. The risk of first events was especially high in the high NTX group. There were no significant correlations between NTX levels and the requirement for palliative radiotherapy alone.

Hazard Ratios for Time to Onset and Occurrence of On-Study SRE Compared With Low (< 50 nmol/mmol creatinine) NTX (P Value)

SREPathologic fracturePalliative radiotherapy
Baseline NTX levelOnset of first SREAny eventOnset of first eventAny eventOnset of first eventAny event
*50 to < 100 nmol/mmol creatinine.; † ≥ 100 nmol/mmol creatinine. 
Moderate* 2.76 (.012) 2.26 (.003) 3.78 (.001) 2.98 (< .001) 1.21 (.777) 1.61 (.386) 
High† 6.80 (< .001) 4.01 (.001) 8.87 (< .001) 5.35 (< .001) 3.23 (.095) 3.44 (.124) 
SREPathologic fracturePalliative radiotherapy
Baseline NTX levelOnset of first SREAny eventOnset of first eventAny eventOnset of first eventAny event
*50 to < 100 nmol/mmol creatinine.; † ≥ 100 nmol/mmol creatinine. 
Moderate* 2.76 (.012) 2.26 (.003) 3.78 (.001) 2.98 (< .001) 1.21 (.777) 1.61 (.386) 
High† 6.80 (< .001) 4.01 (.001) 8.87 (< .001) 5.35 (< .001) 3.23 (.095) 3.44 (.124) 

Conclusions: Multiple myeloma patients with elevated baseline NTX levels have a significantly increased risk of experiencing SREs.

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