The Renal Clearance of Free and Peptide-Bound Deoxypyridinoline: Response to Pamidronate Treatment of Paget's Disease

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Abstract
Bisphosphonate treatment of Paget's disease results in a large decrease in urinary peptide-bound pyridinolines but a smaller decrease in urinary free pyridinolines. This discrepancy could be explained by changes in renal handling of pyridinoline forms. We studied eight patients with Paget's disease treated with pamidronate. We collected blood and urine at baseline and at 3 and 14 days after treatment. We measured free and total deoxypyridinoline (DPD) in serum (S) and urine (U) by high-performance liquid chromatography (HPLC). The ratio of free to total DPD at baseline was (mean ± SE) 13 ± 1% in serum and 37 ± 3% in urine; at 3 days, this had increased to 25 ± 3% in serum and 62 ± 7% in urine. Peptide-bound (pb) DPD decreased significantly 3 days after treatment: UpbDPD -63 ± 11%, p < 0.001; SpbDPD -51 ± 8%, p < 0.01. Free DPD decreased in the urine after 14 days: UfDPD −48 ± 5%, p < 0.01; there was no significant change in SfDPD. The fractional excretion of pbDPD relative to creatinine was less than one at all time-points; however, the fractional excretion of fDPD was significantly greater than one throughout the study. As a consequence, the proportion of free DPD in the urine increased as bone turnover decreased. This resulted in a smaller decrease in urine free compared with peptide-bound DPD in response to bisphosphonate therapy. Thus, the conversion of peptide-bound to free DPD in the kidney may become more efficient as bone turnover decreases as a consequence of pamidronate treatment.

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