A pharmacokinetic interaction study in healthy postmenopausal women demonstrated that there was no interaction between oral 30 mg tamoxifen and intravenous 2 mg ibandronate.

Pharmacodynamics

Osteoporosis is characterized by decreased bone mass and increased fracture risk, most commonly at the spine, hip, and wrist. The diagnosis can be confirmed by a finding of low bone mass, evidence of fracture on x-ray, a history of osteoporotic fracture, or height loss or kyphosis indicative of vertebral fracture. While osteoporosis occurs in both men and women, it is most common among women following menopause. In healthy humans, bone formation and resorption are closely linked; old bone is resorbed and replaced by newly formed bone. In postmenopausal osteoporosis, bone resorption exceeds bone formation, leading to bone loss and increased risk of fracture. After menopause, the risk of fractures of the spine and hip increases; approximately 40% of 50-year-old women will experience an osteoporosis-related fracture during their remaining lifetimes.

In studies of postmenopausal women, BONIVA Injection at doses of 0.5 mg to 3 mg produced biochemical changes indicative of inhibition of bone resorption, including decreases of biochemical markers of bone collagen degradation (cross-linked C-telopeptide of Type I collagen [CTX]). Changes in markers of bone formation (osteocalcin) were observed later than changes in resorption markers, as expected, due to the coupled nature of bone resorption and formation.

Year 1 results from an efficacy and safety study comparing BONIVA Injection 3 mg every 3 months and BONIVA 2.5 mg daily oral tablet demonstrated that both dosing regimens significantly suppressed serum CTX levels at Months 3, 6, and 12. The median pre-dose or trough serum CTX levels in the ITT population reached a nadir of 57% (BONIVA Injection) and 62% (BONIVA 2.5 mg tablets) below baseline values by Month 6, and remained stable at Month 12 of treatment.

Clinical Studies

Daily Oral Tablets

The effectiveness and safety of BONIVA daily oral tablets were demonstrated in a randomized, double-blind, placebo-controlled, multinational study (Treatment Study) of 2946 women aged 55 to 80 years, who were on average 21 years postmenopause, who had lumbar spine bone mineral density (BMD) 2 to 5 SD below the premenopausal mean (T-score) in at least one vertebra [L1-L4], and who had one to four prevalent vertebral fractures. BONIVA was evaluated at oral doses of 2.5 mg daily and 20 mg intermittently. The main outcome measure was the occurrence of new radiographically diagnosed, vertebral fractures after 3 years of treatment. The diagnosis of an incident vertebral fracture was based on both qualitative diagnosis by the radiologist and quantitative morphometric criterion. The morphometric criterion required the dual occurrence of two events: a relative height ratio or relative height reduction in a vertebral body of at least 20%, together with at least a 4 mm absolute decrease in height. All women received 400 IU vitamin D and 500 mg calcium supplementation per day.

Quarterly IV Injection

The effectiveness and safety of BONIVA Injection 3 mg once every 3 months were demonstrated in a randomized, double-blind, multinational, noninferiority study (DIVA Study) in 1358 women with postmenopausal osteoporosis (L2-L4 lumbar spine BMD, T-score below -2.5 SD at baseline). The control group received BONIVA 2.5 mg daily oral tablets. The primary efficacy parameter was the relative change from baseline to 1 year of treatment in lumbar spine BMD, which was compared between the intravenous injection and the daily oral treatment groups. All patients received 400 IU vitamin D and 500 mg calcium supplementation per day.

Effect on Vertebral Fracture

BONIVA 2.5 mg daily oral tablet significantly reduced the incidence of new vertebral and of new and worsening vertebral fractures (Daily Oral Tablet – Treatment Study). Over the course of the 3-year study, the risk for vertebral fracture was 9.6% in the placebo-treated women and 4.7% in the women treated with BONIVA 2.5 mg daily oral tablet (p < 0.001) (see Table 1). In an unapproved regimen, intermittent oral administration of 20 mg BONIVA, involving a 9- to 10-week drug-free interval, produced a statistically significant reduction (50%) in the incidence of new vertebral fractures, similar to that seen with the daily oral 2.5 mg regimen.

Table 1 : Effect of BONIVA Daily Oral Tablet on the Incidence of Vertebral Fracture in the 3-Year Osteoporosis Treatment Study*

Effect on Nonvertebral Fractures

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