Download in pdf format.
Evaluation of Serum Bone Turnover Markers in Renal Dialysis Patients
E.T. Leary¹, M.K. McLaughlin¹, D. Swezey¹, T. Aggoune¹, T.H. Carlson¹, A.P. Foster²
¹Pacific Biometrics, Inc., Seattle, WA ²Roche Diagnostics, Corporation, Indianapolis, IN
Association of Bone and Mineral Research
ASBMR 22nd Annual Meeting, Toronto, Canada
Abstract: JBMR V15 S1, Sept 2000;S525
Chronic renal dialysis patients have compromised bone status and increased bone turnover. This patient group presents special challenges in bone metabolism assessment. More recently, bone turnover markers (BTM) have demonstrated clinical utility in renal patients in spite of the retention and accumulation of some markers. This study compares recently available serum BTMs in 50 renal dialysis patients (21 males and 29 females) age 20 to 85 yrs with dialysis duration of 1 mo to 19 yrs (most under 3 yrs). Fasting serum and plasma samples were collected in the morning. The samples were processed and frozen within 3 hrs and stored at -70°C until analysis for PTH and the following BTMs: serum N-telopeptides by ELISA (sNTx; Ostex International); serum C-telopeptides by Elecsys [sCTx(r); Roche Diagnostics] and by ELISA [sCTx(o); Osteometer BioTech A/S]; bone specific alkaline phosphatase by ELISA (BSAP; Metra Biosystems); osteocalcin by Elecsys [OC(r); Roche Diagnostics] and by IRMA [OC(c); ELSA-OSTEO; CIS bio International]. PTH was by Elecsys [PTH(r); Roche Diagnostics] and by chemiluminescence [PTH(n); Nichols Diagnostics]. In addition, albumin, calcium, creatinine, phosphorous and alkaline phosphatase were measured.
PTH and BTM values in this population were greatly elevated. Overall, the frequency of marker results exceeding the healthy normal ranges were >90% in sNTx, sCTx and OC, >70% in PTH and >30% in BSAP. Comparisons among the BTMs and PTH were listed below as correlation coefficients (r).
|Test||sNTx||sCTx (r)||sCTx (o)||BSAP||OC (r)||OC (c)||PTH (r)||PTH (n)|
The correlation between the resorption markers (sNTX and sCTx) was strong. The correlation between the formation markers, BSAP and OC, and between the formation and resorption markers is poorer, partly due to different renal retention. Assays for the same analyte agreed well, however, the greatly elevated marker values present special demands on the assay design, such as analyte dynamic range, dilution linearity, assay precision and specificity and user friendliness. For example, further dilution was required in 80% of the samples in the sNTx assay, 26% in sCTx (o) and only 2% (one sample) in sCTx(r).
In summary, recently available serum BTMs may be useful in monitoring bone turnover status in the renal dialysis patients. Well-defined sample collection protocol and properly selected assays are important. Stratifying the patients using PTH concentration and normalizing marker values with creatinine may enhance the discriminatory power of the BTM.
Chronic renal failure patients on hemodialysis have compromised bone status. The standard tools for monitoring bone metabolism of these patients are invasive and expensive. This study investigates the potential of emerging serum markers of bone turnover as monitoring tools using a cohort of 50 renal dialysis patients.
MATERIALS AND METHODS
Biomarker Methods Compared
|Product Name||Mfg||Test Code||Products Measured||Test Format|
|ß-Crosslaps™/Serum*||Roche||sCTx (r)||8 AA C-telopeptide
One Step ELISA
|Osteometer||sCTx (o)||8 AA C-telopeptide
|Alkphase-B®||Metra||BAP||BAP epitope & enzyme
|Roche||OC (c)||Intact & main N-terminal
|ELSA-OSTEO*||CIS bio||OC (c)||Intact & main N-terminal
|PTH||Roche||PTH (r)||Intact PTH||Automated/Elecsys|
|INTACT PTH||Nichols||PTH (n)||Intact PTH||Semi-automated|
|Olympus||TAP||Enzyme activity||Automated analyzer|
* For investigational use only.
Marker Concentrations in Renal Dialysis Patients
sNTx-80%; sCTx (o) – 26%; OC (r) – 20%; OC (c) – 12%; sCTx (r), PTH (r) and PTH (c) – 2%; BSAP and TAP – 0%.
Marker Comparison [shown as correlation coefficients (r) on 50 subjects]
|Test||sNTx||sCTx (r)||sCTx (o)||BSAP||OC (r)||OC (c)||PTH (r)*||PTH (n)*||TAP||TAPP**|
*n=49. One subject with PTH level>20,000 pg/mL by both PTH assays was excluded from the statistical analysis (these data were included in the table in the abstract). This subject had normal BAP (27.6 U/L), TAP (70 IU/L), but elevated CTx, NTx and OC. **n=46. Four subjects with elevated TAP that did not fit the among-test correlation pattern were excluded from the estatistical analysis.
Correlation Among Markers with and without Renal Retention
Marker Comparison – Renal vs Non-renally Impaired
SUMMARY AND CONCLUSIONS