Cancer Treatment Today

Lay Summary: Zoledronic acid is avalable as Zometa and as Reclast for osteoporosis. Each formulation has its indications.

Aredia is not FDA indicated for osteoporosis and has no special advantage for this indication over zolendronate. Both pamidronate and zoledronic acid have been shown to reduce bone loss in men undergoing androgen deprivation therapy in prostate cancer. However, zoledronic acid has also been shown to increase bone mineral density in these patients and zoledronic acid has been shown in randomized controlled clinical studies to reduce the incidence of skeletal-related events in men undergoing androgen-deprivation therapy. In addition, zoledronic acid has been shown in clinical trials to reduce the incidence of skeletal events in men with osteoblastic bone metastases from prostate cancer. By contrast, a clinical study comparing pamidronate to placebo control in men with bone metastases due to prostate cancer found no significant differences in incidence of skeletal events between the two groups

Although there is evidence that pamidronate increases bone mass, there are no clinical trials demonstrating that intravenous pamidronate decreases fracture rate in postmenopausal osteoporosis or glucocorticoid-induced osteoporosis.

Zoledronic acid is avalable as Zometa and as Reclast for osteoporosis. Each formulation has its indications.

The United States Pharmacopeial Convention has concluded that zoledronic acid has an established role in prophylaxis of drug-induced osteopenia secondary to androgen-deprivation therapy in prostate cancer patients (USPDI, 2005). Although intravenous zoledronic acid injections have been shown in controlled clinical trials to increase bone density in women with osteoporosis, it has not been shown to decrease the incidence of fractures. As Solomon (2002) commented: “The suggestion that an intravenous dose of zoledronic acid once a year or even less often might effectively treat postmenopausal osteoporosis is encouraging. However, before this treatment can be recommended for routine use, studies are clearly needed to determine whether the risk of fractures is actually reduced and to determine whether long-term use of this medication is safe.” Zometa has been reported to cause jaw osteonecrosis and now a number of other oral biphosphonate alternatives are available.

However, subsequntly the FDA approved Reclast, a different preparation of zoledronic acid for once annual infusion for treatment of osteoporosis. New Phase III data presented for the first time demonstrated that the investigational treatment Reclast(R)^ (zoledronic acid) 5 mg was highly effective in reducing the incidence of bone fracture in women with postmenopausal osteoporosis across the most common fracture sites — hip, spine and non-spine^^ — with sustained effect over three years. Further data demonstrated that postmenopausal osteoporosis patients currently taking oral alendronate can be directly switched to Reclast and maintain beneficial bone effects for a full 12 months after a single dose. These studies were presented at the annual meeting of the American Society of Bone and Mineral Research (ASBMR) in Philadelphia.

In vivo animal studies suggest that exemestane may be more bone sparing than letrozole, owing to its androgenic structure. However, there are no human trials showing a differential effect of the individual AIs on bone.

Whereas Zometa is 4 mg and usually given once monthly for active cancer and biannually for osteoporosis, Reclast is a 5 mg dose and can be given even  when there is no cancer. The breast cancer literature supports twice annual Zometa for prevention of osteporosis for women placed on adjuvant arimidex. The details of one randomized trial were published as an early online report in the Journal of Clinical Oncology on December 11, 2006. Either formulation of Zometa is acceptable for osteoporosis, or as in this patient, osteopenia under active exemestane therapy as indicated and represents standard of care.

Reclast is indicated for treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, diagnosed by bone mineral density (BMD) or prevalent vertebral fracture, Reclast reduces the incidence of fractures (hip, vertebral and non-vertebral osteoporosis-related fractures). In patients at high risk of fracture, defined as a recent low-trauma hip fracture, Reclast reduces the incidence of new clinical fractures
Gnant MFX, Mlineritsch B, Luschin-Ebengreuth G et al. Zoledronic Acid Effectively Prevents Cancer Treatment-induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-responsive Breast Cancer: A Report from the Austrian Breast and Colorectal Cancer Study Group. Journal of Clinical Oncology. Early online publication December 11, 2006.

Brufsky AM et al, Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results.Clin Breast Cancer. 2009 May;9(2):77-85.

AU Safra T, Bernstein-Molho R, Greenberg J, Pelles-Avraham S, Stephansky I, Sarid D, Inbar MJ, Stemmer SM, Geffen DB The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial.
Oncology. 2011;81(5-6):298-305.

Black DM, et al. Effect of once-yearly infusion of Zoledronic Acid 5 mg on spine and hip fracture reduction in postmenopausal women with osteoporosis: the HORIZON pivotal fracture trial. Presented at 28th Annual meeting of the American Society for Bone and Mineral Research (ASBMR), 15-19 September 2006, Philadelphia, USA.

McClung M, et al. Single infusion of zoledronic acid 5 mg provides sustained benefits in BMD and biomarkers at 12 months in postmenopausal women with low bone mineral density and prior alendronate therapy. Presented at 28th Annual meeting of the American Society for Bone and Mineral Research (ASBMR), 15-19 September 2006, Philadelphia, USA.

Ward L, Tricco AC, Phuong P, et al. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007;(4):CD005324.
Julie R. Gralow, MD; J. Sybil Biermann, MD; Azeez Farooki, MD;
Monica N. Fornier, MD; Robert F. Gagel, MD; Rashmi Kumar, PhD;
Georgia Litsas, MSN, ANP-BC, AOCNP; Rana McKay, MD;
Donald A. Podoloff, MD; Sandy Srinivas, MD; and
Catherine H. Van Poznak, MDNCCN Task Force Report:
Bone Health in Cancer Care. JNCCNJournal of the National Comprehensive Cancer Network
Volume 11 Supplement 3,   August 2013