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Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases.
J Bone Miner Res. 2005 Sep; 20(9):1543-7.JB

Abstract

Bisphosphonate pharmacokinetics may affect individual responses. Skeletal retention of pamidronate infused monthly to patients with bone metastases was highly variable (12-98%) and did not diminish with time, showing the capacity of the skeleton to retain large amounts of bisphosphonate. Relationships between skeletal retention of pamidronate and rate of bone resorption are complex and depend on previous treatment and the total amount of retained bisphosphonate.

INTRODUCTION

Bisphosphonates (BPs) given intravenously every 3-4 weeks are effective in the management of metastatic bone disease from breast cancer, but responses among patients vary, and it is not known whether current dose and dose intervals are appropriate for an individual patient. An influence of pharmacokinetics of BPs on antiresorptive action may contribute to this variation in response. To test this hypothesis, we determined the skeletal retention of intravenous pamidronate and its association to the rate of bone resorption in patients with bone metastases from breast cancer.

MATERIALS AND METHODS

In a cross-sectional study, 24-h urinary excretion of pamidronate and the biochemical marker of bone resorption N-terminal telopeptide of type 1 collagen and serum alkaline phosphatase were measured in 40 patients with bone metastases from breast cancer at the beginning, after 3-6 months, and after 1 year of treatment with intravenous pamidronate 90 mg every 3-4 weeks.

RESULTS AND CONCLUSIONS

Skeletal retention (dose--amount excreted into urine) 2 days after infusion varied between 12% and 98% (mean, 62%) of the administered dose, but there were no differences in retention between patients receiving pamidronate for the first time or after 3-6 months or after 1 year of treatment. Retention of pamidronate was related to the prevalent rate of bone turnover in previously untreated patients, whereas no such relationship was found in previously treated patients. Rate of bone resorption after treatment seemed to be related to the amount of pamidronate retained. During 1 year of treatment, retention of pamidronate remained constant, indicating no saturation of skeletal binding sites with treatment. The variability in retention among individual patients can be attributed to the number of available binding sites. This is related, however, to bone turnover only before the start of treatment. The apparent relationships between skeletal retention and antiresorptive effect could have implications for the design of optimal therapeutic regimens with BPs in patients with bone metastases from breast cancer.

Authors+Show Affiliations

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16059626

Citation

Cremers, Serge C L M., et al. "Skeletal Retention of Bisphosphonate (pamidronate) and Its Relation to the Rate of Bone Resorption in Patients With Breast Cancer and Bone Metastases." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 20, no. 9, 2005, pp. 1543-7.
Cremers SC, Papapoulos SE, Gelderblom H, et al. Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases. J Bone Miner Res. 2005;20(9):1543-7.
Cremers, S. C., Papapoulos, S. E., Gelderblom, H., Seynaeve, C., den Hartigh, J., Vermeij, P., van der Rijt, C. C., & van Zuylen, L. (2005). Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 20(9), 1543-7.
Cremers SC, et al. Skeletal Retention of Bisphosphonate (pamidronate) and Its Relation to the Rate of Bone Resorption in Patients With Breast Cancer and Bone Metastases. J Bone Miner Res. 2005;20(9):1543-7. PubMed PMID: 16059626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases. AU - Cremers,Serge C L M, AU - Papapoulos,Socrates E, AU - Gelderblom,Hans, AU - Seynaeve,Caroline, AU - den Hartigh,Jan, AU - Vermeij,Pieter, AU - van der Rijt,Carin C D, AU - van Zuylen,Lia, Y1 - 2005/05/31/ PY - 2004/12/15/received PY - 2005/05/09/revised PY - 2005/05/27/accepted PY - 2005/8/2/pubmed PY - 2006/1/5/medline PY - 2005/8/2/entrez SP - 1543 EP - 7 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 20 IS - 9 N2 - UNLABELLED: Bisphosphonate pharmacokinetics may affect individual responses. Skeletal retention of pamidronate infused monthly to patients with bone metastases was highly variable (12-98%) and did not diminish with time, showing the capacity of the skeleton to retain large amounts of bisphosphonate. Relationships between skeletal retention of pamidronate and rate of bone resorption are complex and depend on previous treatment and the total amount of retained bisphosphonate. INTRODUCTION: Bisphosphonates (BPs) given intravenously every 3-4 weeks are effective in the management of metastatic bone disease from breast cancer, but responses among patients vary, and it is not known whether current dose and dose intervals are appropriate for an individual patient. An influence of pharmacokinetics of BPs on antiresorptive action may contribute to this variation in response. To test this hypothesis, we determined the skeletal retention of intravenous pamidronate and its association to the rate of bone resorption in patients with bone metastases from breast cancer. MATERIALS AND METHODS: In a cross-sectional study, 24-h urinary excretion of pamidronate and the biochemical marker of bone resorption N-terminal telopeptide of type 1 collagen and serum alkaline phosphatase were measured in 40 patients with bone metastases from breast cancer at the beginning, after 3-6 months, and after 1 year of treatment with intravenous pamidronate 90 mg every 3-4 weeks. RESULTS AND CONCLUSIONS: Skeletal retention (dose--amount excreted into urine) 2 days after infusion varied between 12% and 98% (mean, 62%) of the administered dose, but there were no differences in retention between patients receiving pamidronate for the first time or after 3-6 months or after 1 year of treatment. Retention of pamidronate was related to the prevalent rate of bone turnover in previously untreated patients, whereas no such relationship was found in previously treated patients. Rate of bone resorption after treatment seemed to be related to the amount of pamidronate retained. During 1 year of treatment, retention of pamidronate remained constant, indicating no saturation of skeletal binding sites with treatment. The variability in retention among individual patients can be attributed to the number of available binding sites. This is related, however, to bone turnover only before the start of treatment. The apparent relationships between skeletal retention and antiresorptive effect could have implications for the design of optimal therapeutic regimens with BPs in patients with bone metastases from breast cancer. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/16059626/Skeletal_retention_of_bisphosphonate__pamidronate__and_its_relation_to_the_rate_of_bone_resorption_in_patients_with_breast_cancer_and_bone_metastases_ L2 - https://doi.org/10.1359/JBMR.050522 DB - PRIME DP - Unbound Medicine ER -