Zoledronic acid (Zometa)

Inhibits osteoclastic bone resorption by attaching to hydroxyapatite binding sites on bony surfaces.

The incorporated bisphosphonate impairs the ability of osteoclast to adhere to the bony surface, and also inhibits the stimulation of bone resorption.

A bisphosphonate associated with acute renal failure and acute tubular necrosis and osteomyelitis/osteonecrosis of the jaw.

Reduces skeletal related events in breast cancer, myeloma and prostate cancer.

Treatment with bone-protecting agents (BPAs) zoledronic acid or denosumab entirely eliminated the risk of fracture as seen in a study of men with metastatic castration-resistant prostate cancer (CRPC) treated with enzalutamide alone or in combination with radium-223.

Its  use mitigates the rebound phenomenon associated with denosumab discontinuation.

Zoledronic acid is the only bisphosphonate shown to confer a survival advantage in myeloma.

Reduces skeletal related events in patients with NSCLC but does not increase survival.

By adding zoledronic acid to endocrine treatment significantly prolongs disease free survival and recurrence with survival versus endocrine therapy alone in premenopausal women with hormonally responsive breast cancer by 36% and 35% respectively (Gnant).

Australian Breast and Colorectal Cancer Study Group trial 12 indicated that adding zoledronic acid to adjuvant hormonal therapy for 3 years reduced the risk of disease progression by 36% in 1803 premenopausal women with stage I or II endocrine responsive breast cancer (Gnant M et al).

AZURE trial of 3360 women (pre and postmenopausal women) with stage II or III breast cancer 96% of whom received adjuvant chemotherapy, and only 152/3360 receiving hormonal treatment alone, study group received zoledronic acid (4mg every 3-4 weeks x 6 doses, then every 6 months for 5 additional doses) median follow-up 59 months:no difference in local recurrence or death, but postmenopausal women for more than 5 years or at least 60 years old had a 29 % reduced risk of dying of breast cancer.

Adjuvant therapy with zoledronic should be considered to improve survival of women with premenopausal breast cancer.

A once yearly infusion for the treatment of osteoporosis, Pagets disease of the bone, or for the prevention or treatment glucocorticoid induced osteoporosis has been approved by the FDA(Reclast).

Reclast, the annual infusion of zoledronic acid reportedly may cause impaired renal function or acute renal failure, and this is particularly true if the patients are taking concurrent nephrotoxicity medications.

Patients who received this agent should be properly hydrated before its administration, it should be administered over at least 15 minutes with subsequent monitoring of serum creatinine levels.

In the ZO-FAST study ( Zometa-Femara Adjutant Synergy Trial), and open labeled randomized phase 3 trial of 1065 postmenopausal women with early breast cancer receiving letrozole 2.5 mg a day for five years were randomized to receive zoledronic acid immediately or zoledronic acid if they are BMD T score fell below -2 or a fragility fracture was present: the mean change of L2-L4 BMD at 36 months was +4.39% for the immediate treatment group versus -4.9% for the delayed treatment group, and the disease free survival was significantly improved in the immediate treatment arm compared with the delayed treatment arm (Eidtmann et al).

In the SUCCESS-A trial 2987 women randomized to receive Zoledronic acid either for five years at 4 mg IV every three months or for two years:Patient’s had invasive breast cancer at high risk for recurrence, either note positive no negative for the tumor size greater than 2 cm, grade 3, negative hormone receptor status, or in women 35 years or younger.
In the SUCCESS-A trial there was no significant difference in point of disease free survival for women receiving five years or two years of adjuvant zoledronate (Friedl).

In the above study the immediate treatment group at 36 months had a 41% relative risk reduction for disease free survival events.

In a open labeled study, phase 3, randomly assigning 3360 patients to receive standard adjuvant systemic therapy with or without zoledronic acid with zoledronic acid dispute every 3-4 weeks for six doses and then every 3-6 months to complete five years of treatment: at a median follow-up of 59 months no significant difference in the rate of disease free survival was noted-findings would not support the routine use of zoledronic as an adjuvant management of breast cancer (Coleman RE et al).

Zoledronic acid (Reclast) at a 5 mg dose once a year as anti-fracture efficacy in postmenopausal females with osteoporosis.

In a six year, double-blind trial involving 2000 women with osteopenia at either the total hip or the femoral neck and treated with placebo versus zoledronate: the risk of non-vertebral vertebral fragility fracture was significantly lower in the women with osteopenia who received zoledronic acid then and women who receives the placebo (Reid IR).

Zoledronic acid (Reclast) at a 5 mg dose once a year as anti-fracture efficacy in men with positive effects on bone mineral density.

Zoledronic acid reduces the risk of height loss and moderate to severe vertebral fractures.

Also reduces the risk of non-vertebral fractures.

Administered by intravenous injection at intervals of one year or longer, and it is preferred over oral bidphosphonates by a majority of patients, and has a satisfactory safety profile.

In any multicentered, double-blind, placebo-controlled trial 1199 then with primary or hypogonadism related osteoporosis 50-85 years of age to receive infusions of zoledronic acid or placebo: There was a significantly reduced risk of vertebral fracture among men with osteoporosis treated with zoledronic acid (Boonen S et al).

In patients with bone metastases from solid tumors who received zoledronic acid 4 mg IV every 3-4 weeks associated with a lower monthly rate of skeleton related complications compared with other dosing schedules and no treatment (Hatoum HT).

Dosing interval now recommended to be extended from 4 to 12 weeks to reduce the risk of skeletal related events in metastatic breast cancer, metastatic prostate cancer, and multiple myeloma.

In high risk prostate cancer patients the treatment with hormone therapy and the addition of zoledronic acid did not increase survival (James ND et al).

Common adversity, effects for zoledronate include, systemic inflammatory symptoms, and chronic renal toxicity.

Severe adverse events include hypocalcemia, atypical femoral fractures, and osteoporosis of the jaw.


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