Reclast (zoledronic acid)

Reclast (zoledronic acid) is is a bisphosphonic acid inhibitor of osteoclastic bone resorption. Once administered, it rapidly moves to bone and preferentially localizes at sites of high bone turnover.

Reclast is specifically indicated for treatment of osteoporosis in postmenopausal women.

Reclast is supplied as 5 mg in a 100 mL ready to infuse solution for intravenous administration. The recommended initial dose of the drug is a 5 mg infusion once a year given intravenously over no less than 15 minutes.

FDA Approval
FDA approval of Reclast was based on the results of a clinical trial. This randomized, double-blind, placebo -controlled, multinational study enrolled 7,736 women aged 65-89 years with osteoporosis. The subjects were stratified into two groups Stratum I: no concomitant use of osteoporosis therapy or Stratum II: baseline concomitant use of osteoporosis therapies which included calcitonin, raloxifene, tamoxifen and hormone replacement therapy. Reclast was administered once a year for three consecutive years, as a single 5 mg dose in 100 mL solution infused over at least 15 minutes, for a total of three doses. All subjects received 1000 to 1500 mg of elemental calcium plus 400 to 1200 IU of vitamin D supplementation per day. The subjects in Stratum I were evaluated annually for incidence of vertebral fractures. The subjects in Stratum I and II were evaluated for the incidence of hip and other clinical fractures. The primary endpoints were the incidence of morphometric vertebral fractures at 3 years and the incidence of hip fractures over a median duration of 3 years.

Effect on vertebral fractures over three years
Reclast significantly reduced the incidence of new vertebral fractures over three years compared to placebo. In the Reclast arm, there was a 3.3% rate of at least one new vertebral fracture versus 10.9% in the placebo arm (p <0.0001) for a 7.6% absolute reduction in fracture incidence and 70% reduction in fracture incidence.

Effect on hip fracture over three years
Reclast demonstrated a 1.1% absolute reduction and 41% relative reduction in the risk of hip fractures over a median duration of 3 years. The hip fracture event rate was 1.4% for Reclast -treated subjects compared to 2.5% for placebo -treated subjects.

Reclast also had a positive effect over placebo in the following areas:

Bone Mineral Density
Reclast significantly increased BMD at the lumbar spine, total hip and femoral neck, relative to treatment with placebo at time points 12, 24, and 36 months. Treatment with Reclast resulted in a 6.7% increase in BMD at the lumbar spine, 6.0 % at the total hip, and 5.1% at the femoral neck, over 3 years as compared to placebo.

Bone Histology
Bone biopsy specimens were obtained between months 33 and 36 from 82 subjects treated with 3 annual doses of Reclast. Qualitative, quantitative and micro CT assessments showed bone of normal architecture and quality without mineralization defects.

Effect on Height
Over the three-year study standing height was measured annually using a stadiometer. The Reclast group revealed less height loss compared to placebo (4.2 mm vs. 7.0 mm, respectively (p<0.001)).

Adverse events associated with the use of Reclast may include, but are not limited to, the following:

• Arthralgia
• Pyrexia
• Hypertension
• Headache
• Myalgia
• Pain in Extremity
• Influenza-like Illness
• Nausea

Reclast is a bisphosphonic acid inhibitor of osteoclastic bone resorption. Once administered, it rapidly moves to bone and preferentially localizes at sites of high bone turnover. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase which catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways.

Devogelaer JP, Brown JP, Burckhardt P, Meunier PJ, Goemaere S, Lippuner K, Body JJ, Samsioe G, Felsenberg D, Fashola T, Sanna L, Ortmann CE, Trechsel U, Krasnow J, Eriksen EF, Garnero P Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis. Osteoporosis International 2007 Sep;18(9):1211-8

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. The New England Journal of Medicine 2007 May 3;356(18):1809-22

Rackoff PJ, Sebba A Optimizing administration of bisphosphonates in women with postmenopausal osteoporosis. Treatments in Endocrinology 2005;4(4):245-51

Sartori L, Adami S, Filipponi P, Crepaldi G Injectable bisphosphonates in the treatment of postmenopausal osteoporosis. Aging Clinical and Experimental Research 2003 Aug;15(4):271-83

Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ Intravenous zoledronic acid in postmenopausal women with low bone mineral density. The New England Journal of Medicine 2002 Feb 28;346(9):653-61

For additional information regarding Reclast or postmenopausal osteoporosis, please visit the Reclast web page.