Elimination and Biochemical Responses to Intravenous Alendronate in Postmenopausal Osteoporosis

Abstract

Postmenopausal women with established vertebral osteoporosis were studied for 2 years to determine the terminal elimination half-life and the duration of response to treatment with intravenous alendronate (30 mg) given over 4 days. The urinary excretion of alendronate followed a multiexponential decline. Approximately 50% of the total dose was excreted over the first 5 days, and a further 17% was excreted in the succeeding 6 months. Thereafter, there was a much slower elimination phase with an estimated mean terminal half-life of greater than 10 years (n ‫؍‬ 11). Urinary excretion of hydroxyproline and calcium decreased significantly from pretreatment values by day 3, reaching a nadir by 1 week (40% and 67% decrease, respectively). Thereafter, hydroxyproline remained suppressed for the following 2 years. In contrast, urinary calcium excretion returned gradually toward pretreatment values over the first year and during the second year was comparable to pretreatment values. Serum activity of alkaline phosphatase activity decreased over 3 months (23% reduction), increased gradually thereafter, and returned to pretreatment values at month 24. Bone mineral density measured at the spine increased by approximately 5% during the first year and remained significantly higher than pretreatment values at 2 years. We conclude that a short course of high doses of intravenous alendronate is associated with a prolonged skeletal retention of the agent. This open study also suggests that this regimen has a sustained effect on bone turnover persisting for at least 1

Skeletal Retention of Bisphosphonate (Pamidronate) and Its Relation to the Rate of Bone Resorption in Patients With Breast Cancer and Bone Metastases

“…Relationships between the amount of BP in the skeleton and suppression of bone resorption have been reported previously in other bone diseases, which also revealed the complexities of the PK and PK/PD relationships of BPs. (9)(10)(11) BPs decrease significantly skeletal-related events in patients with bone metastases and have been also reported to decrease the incidence of new bone metastases. (12)(13)(14) Because of this, they are routinely used in the management of patients with breast cancer metastatic to the skeleton.…”

“…2, but this underestimation was relatively small, as shown previously in studies of patients with Paget's disease of bone and osteoporosis treated with BPs. (10,11) This study provides more insight into the potential role of PK and PK/PD relationships of BPs in the management of breast cancer metastatic to bone. Such relationships may, at least partly, account for differences in response to BP treatment among individual patients and their further study can help in improving BP treatment of metastatic bone disease.…”

Adverse Effects of Bisphosphonates: Implications for Osteoporosis Management

“…4 Although the precise biological half-lives of nitrogen-containing bisphosphonates in bone remain poorly characterized, it is estimated to be at least 10 years. 5 …”

Treatment of established osteoporosis: a systematic review and cost-utility analysis

“…A sustained effect of bisphosphonates was observed following a short course of alendronate in the treatment of osteoporosis. 207,208 Recent studies of the use of pamidronate and alendronate have suggested, however, that bone loss may eventually resume at an accelerated rate. 209,210 Similar findings have been reported for risedronate.…”