Prolonged Efficacy of a Single Dose of the Bisphosphonate Zoledronic Acid

Abstract

Purpose: Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment^induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration.Experimental Design: Sixty-six patients who were osteopenic at >1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay. Results: The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively (P < 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was f58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively (P < 0.001).Conclusions: A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption.Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.

Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01–04) for women with stage II/III breast cancer

“…In another series of patients who received bisphosphonates (not ZOL) within 12 months of conception or during the first trimester of pregnancy (n = 21), no increased risk of birth defects was seen [29]. We could not find any published reports regarding exposure to ZOL and pregnancy outcome, but concerns regarding foetal development remain because of the potency and long offset duration of ZOL [31].…”

A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration

“…Recently, the bisphosphonate zoledronic acid (ZOL) has been approved for the treatment of osteoporosis due to its beneficial effect on bone mass [14,15]. This drug has a high affinity for hydroxyapatite and binds directly to mineralized bone [16].…”

Bone recovery after zoledronate therapy in thalassemia-induced osteoporosis: a meta-analysis and systematic review

“…Additionally, it has been shown that zoledronic acid therapy can also augment erythropoetic activity [20] and that even after cessation of zoledronate therapy there continues to be a long-term improvement in BMD [21]. The latter finding is especially important in the light of other observations [36,37], which suggest that it may be possible to reduce the cost of zoledronate therapy by reducing the number of zoledronate doses. Recent data also suggest that the efficacy of zoledronate therapy might depend on the other genotypes like that in the genes encoding the vitamin D receptor [15] and bone type I collagen [23].…”