Effect of Antiresorptive Therapy on Day-to-Day Variation of Urinary Free Deoxypyridinoline Excretion

Instituto de Investigaciones Metabolicas, Libertad 836 1er piso, (1012) Buenos Aires, Argentina
^a Author for correspondence. Fax 54 1 816-1495; e-mail efradinger{at}idim.com.ar.

To the Editor:

Measurement of bone markers provides information about bone resorption and formation. One of the proposed clinical applications is to monitor antiresorptive therapy (1); however, this could be precluded because bone markers show day-to-day and circadian variation (2)(3)(4)(5)(6). High intraindividual variation might be the principal cause of limited utility in the individual patient. Most of the studies on variability were done in untreated individuals. Therefore we decided to evaluate the effect of antiresorptive therapy on day-to-day variation of urinary free deoxypyridinoline (DPD).

Eight postmenopausal women (mean age, 62.5 ± 3.9 years) were studied. They all had osteoporosis (defined according WHO densitometric criteria) and pretherapy baseline DPD values above the upper limit of the reference interval (3–8 µmol/mol creatinine) with a mean ± SD of 10.83 ± 2.81 µmol/mol creatinine. Women were placed on therapy (10 mg of alendronate plus evening supplementation of 1000 mg calcium) for at least 6 months. Day-to-day variability was studied after 6 months to avoid the period of very dynamic changes in DPD as it responds to treatment. Five second-void morning urine samples were collected with 2-day intervals for each patient. Samples were all collected between 0800 and 1000 because untimed urine collections would potentiate intraindividual variability. DPD was measured by ELISA (Pyrilinks-D, Metra Biosystems) following the manufacturer's instructions. All 40 samples were measured in duplicate in one batch, and results are expressed as µmol DPD/mol creatinine. The within-run analytical imprecision (CV) was <4%. The mean day-to-day CV was 12%, with a range of 5–15%. These values were considerably lower than those reported for untreated premenopausal women (mean CV, 16%; range, 7–25%) (4). To our knowledge, these are the first data on day-to-day variation of bone resorption markers under treatment. The lower variation observed herein would be explained by changes in the diurnal rhythm induced by treatment. Sarainen et al. (7), in a short-term treatment with clodronate, observed a nonsignificant trend in suppression of the diurnal rhythm of cross-linked N-telopeptides of type I collagen (NTx) excretion and no indication of such suppression in two other markers of bone resorption. Greenspan et al. (8) found no effect of 5 mg/day alendronate on the day-night difference in NTx excretion. Thus, although our patients received a different dose (10 mg/day), an alendronate-induced alteration of the diurnal rhythm in DPD excretion seems unlikely. On the other hand, Blumsohn et al. (9) reported that evening supplementation with 1000 mg of calcium completely abolished the diurnal rhythm of total DPD. Therefore, in our patients calcium supplementation may have reduced day-to-day variability by a reduction of diurnal variation of DPD excretion. Additional studies are needed to completely clarify this issue.

After 6 months of antiresorptive therapy, DPD concentrations in all women decreased to within the reference interval from pretherapy baseline concentrations. The mean ± SD decrease was 46% ± 14% (range, 25–64%). As shown in Fig. 1 , individual values remained within the reference interval over 5 nonconsecutive days. This suggests that information of bone status provided by DPD during antiresorptive therapy is consistent even when the highest CV value reached 15%.

View larger version (20K): [in this window] [in a new window]   Figure 1. Day-to-day variation of urinary free DPD excretion in eight patients under antiresorptive therapy during 5 nonconsecutive days. Dashed lines denote DPD reference interval.

In conclusion, we observed—in a short-term study—a lower day-to-day variation of DPD during antiresorptive therapy than those reported for untreated individuals. This suggests that DPD measurements could provide useful clinical information in the individual patient to appropriate interpretation of bone status and antiresorptive treatment effects. Moreover, these observations point out the need for additional long-term studies to confirm the clinical utility of DPD measurements in patients under antiresorptive therapy.

References

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