Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis

Abstract

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n = 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p = 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p = 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.

Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis

“…Bisphosphonates are today's worldwide leading medication [7][8][9][10][11][12][13][14][15][16] and are recommended as first-line treatments for osteoporosis [1,2,17,18]. Two chemically distinct groups of bisphosphonates exist: Simple non-nitrogen-containing bisphosphonates (Non-N-BP's, e.g., Etidronate) and nitrogen-containing bisphosphonates (N-BP´s) e.g., Ibandronate, Alendronate, Zoledronate and Risedronate).…”

“…There are two fundamentally, distinct components of the mechanism of action of nitrogen containing bisphosphonates (N-BPs) [19,20]: These are 1) binding to the bone, and 2) binding to and inhibition of a key osteoclast enzyme farnesyl pyrophosphate synthase (FPPS). Regarding the oral bisphosphonates, only Risedronate and Alendronate have been proven to reduce vertebral and hip fracture risk in clinical trials [8][9][10][11][12][13][14][15][21][22][23][24]. Zoledronate is an intravenous bisphosphonate therapy and has also been proven to reduce vertebral and hip fracture risk in clinical trials.…”

Postmenopausal osteoporosis treatment with antiresorptives: Effects of discontinuation or long-term continuation on bone turnover and fracture risk—a perspective

“…Levels of urinary N-telopeptide of type I collagen (NTx) rose after discontinuation but remained significantly below the pretreatment baseline value at the end of the follow-up year. (53) In a 2-year extension of a 3-year randomized, controlled trial (RCT) in which participants continued receiving placebo or risedronate according to their original randomization, (55) spine BMD of patients receiving risedronate increased gradually throughout the 5 years, while BMD at the hip (femoral neck and trochanter) increased during the first 3 years (56) and then plateaued (Table 1). (55) Urinary NTx levels decreased by 50% during the first 3 months of treatment and remained at this level for the 5 years of treatment (Fig.…”

Bisphosphonates

“…In patients with osteoporosis, bisphosphonate therapy results in clinically relevant reduction in the incidence of vertebral and non-vertebral fractures (including hip fractures) (10,12,(17)(18)(19)(20)(21). Fracture protection occurs within a few months of beginning therapy (10,12,(22)(23)(24) and is sustained for at least several years (19,25).…”

“…Fracture protection occurs within a few months of beginning therapy (10,12,(22)(23)(24) and is sustained for at least several years (19,25). Importantly, the cycle of progressive, multiple vertebral fractures is reduced by 77-96% (10,18,20).…”