Risedronate sodium is used in the prevention and treatment of osteoporosis in postmenopausal women and in the prevention and treatment of corticosteroid-induced osteoporosis in men and women. Risedronate also is used for the treatment of Paget's disease of bone (osteitis deformans). Risedronate sodium copackaged with calcium carbonate is used for the prevention and treatment of osteoporosis in postmenopausal women.
All patients with osteoporosis or who were at risk for development of osteoporosis in clinical trials of risedronate received concomitant therapy with calcium. Patients with osteoporosis or Paget's disease of bone who are receiving risedronate should receive supplemental calcium and vitamin D if their daily dietary intake is inadequate.
Prevention in Postmenopausal Women
Risedronate is used for the prevention of osteoporosis in postmenopausal women. Risk factors include premature ovarian failure, a family history of osteoporosis, a small, slim body frame, cigarette smoking, drinking excessive amounts of alcohol, low dietary calcium intake, a sedentary lifestyle, and Caucasian or Asian race. For additional information on osteoporosis,
In a double-blind, placebo-controlled study in early postmenopausal women (42-63 years of age), risedronate sodium administration (5 mg daily for 2 years) was associated with an increase in bone mineral density (BMD) in the lumbar spine, femoral neck, and trochanter bone compared with placebo. In another study, increases in BMD in the femoral neck and midshaft radius were observed in postmenopausal women (37-82 years of age) with osteopenia who received risedronate sodium (5 mg daily for 1 year) and conjugated estrogens (0.625 mg daily) compared with those who received conjugated estrogens without risedronate. Bone histology studies in postmenopausal women treated with risedronate sodium 5 mg daily plus estrogen indicate that the bone formed had normal lamellar structure and mineralization.
Efficacy of risedronate 35 mg once weekly for the prevention of osteoporosis was evaluated in a randomized, double-blind, placebo-controlled study in 278 postmenopausal women. All women received daily supplementation with vitamin D (400 units) and calcium (1 g). After 1 year of treatment, risedronate substantially increased BMD at the lumbar spine, total proximal femur, femoral neck, and trochanter compared with placebo (least-square mean increase in BMD of 2.9, 1.5, 1.2, and 1.8%, respectively).
Treatment in Postmenopausal Women
Risedronate is used in the treatment of osteoporosis in postmenopausal women. In placebo-controlled studies in postmenopausal women with osteoporosis, therapy with risedronate sodium 5 mg daily for 2-3 years substantially increased BMD in the lumbar spine, femoral neck, and femoral trochanter and maintained BMD at the midshaft radius while patients treated with placebo lost BMD at all sites. Bone histology studies in postmenopausal women with osteoporosis treated with risedronate sodium 5 mg daily indicate that bone formed during treatment with the drug is of normal quality. Risedronate therapy reduced the incidence of vertebral and nonvertebral (e.g., wrist, humerus, hip, pelvis, leg) fractures among postmenopausal women with osteoporosis who had previously sustained vertebral fractures.
In a 1-year controlled study in postmenopausal women with osteoporosis, risedronate sodium 35 or 50 mg once weekly produced increases in lumbar spine and hip BMD similar to those observed with a dosage of 5 mg daily.
In 2 double-blind trials, risedronate sodium in a monthly dosage of 150 mg was found to be noninferior to a regimen of 5 mg daily in increasing BMD. Risedronate was administered as a single 150-mg tablet once a month in one of the studies and as a 75-mg tablet on 2 consecutive days each month in the other study. In both studies, the mean change in BMD for the lumbar spine and other skeletal sites was similar between the monthly and daily dosing regimens.
Treatment in Men
Risedronate is used for the treatment of osteoporosis in men to increase bone mass. Efficacy and safety of the drug for this use is based principally on results of a double-blind, placebo-controlled study in men 36-84 years of age (mean age: 60.6 years) with osteoporosis (defined as a femoral neck BMD of at least 2 standard deviations below the normal adult mean and a lumbar spine BMD of at least 1 standard deviation below the normal adult mean, or a femoral neck BMD of at least 1 standard deviation below the normal adult mean and a lumbar spine BMD of at least 2.5 standard deviations below the normal adult mean). All patients received supplemental calcium (1 g daily) and vitamin D (400-500 units daily). Treatment with risedronate 35 mg once weekly substantially increased BMD in the lumbar spine, femoral neck, trochanter, and total hip compared with placebo (mean treatment differences of 4.5, 1.1, 2.2, and 1.5%, respectively). Increases in BMD were apparent as early as 6 months (the earliest time point tested) after initiation of risedronate therapy. Few vertebral and nonvertebral fractures were reported in this study, and no difference in fracture rates was observed between the treatment groups.
Risedronate sodium is used for the prevention and treatment of corticosteroid-induced osteoporosis. The manufacturer recommends use of risedronate for the treatment of corticosteroid-induced osteoporosis in men and women who are either initiating or continuing systemic corticosteroid therapy for chronic disease in a daily dosage equivalent to at least 7.5 mg of prednisone.
The American College of Rheumatology (ACR) currently recommends use of a bisphosphonate (i.e., alendronate, risedronate, or zoledronic acid) in conjunction with lifestyle modification and calcium and vitamin D supplementation for the prevention and treatment of corticosteroid-induced osteoporosis in select postmenopausal women and men 50 years of age or older who are initiating or currently receiving corticosteroid therapy. ACR recommendations are based on a risk-stratification approach in which a patient's clinical risk level for developing a fracture is determined, guided in part by the FRAX risk assessment tool (which employs variables such as gender, age, race/ethnicity, and femoral neck density) and the patient's preexisting or anticipated corticosteroid dosage. ACR states that because of limited data, use of bisphosphonates for prevention or treatment of corticosteroid-induced osteoporosis in premenopausal women and men younger than 50 years of age can be recommended only in those who have a history of fragility fracture. For additional details on the use of bisphosphonates for prevention and treatment of corticosteroid-induced osteoporosis, .
Bisphosphonate therapy has resulted in significant increases in BMD (most consistently in the lumbar spine) in patients with a variety of corticosteroid-treated conditions, most commonly rheumatoid arthritis or polymyalgia rheumatica, and such beneficial effects generally occurred irrespective of patient age, gender, or female menopausal status. For additional information on the minimization of risk of corticosteroid-induced bone loss, .
Risedronate is used in the prevention of corticosteroid-induced osteoporosis in men and women initiating therapy with corticosteroids in a daily dosage equivalent to at least 5 mg of prednisone.
In a placebo-controlled, double-blind, randomized study, risedronate sodium 5 mg daily for 1 year prevented bone loss in men and women with a variety of underlying diseases (e.g., rheumatoid arthritis, temporal arteritis, polymyalgia rheumatica, systemic lupus erythematosus, asthma) who had initiated corticosteroid therapy within 3 months of study entry and had normal mean lumbar spine BMD. BMD was maintained or increased in patients receiving risedronate while patients receiving placebo experienced decreases in BMD at the lumbar spine, femoral neck, and trochanter. In patients who underwent bone biopsies at the end of the study, bone histology was normal in patients receiving risedronate and corticosteroids.
Risedronate is used in the treatment of corticosteroid-induced osteoporosis in men and women receiving corticosteroids in a daily dosage equivalent to at least 5 mg of prednisone.
In patients with corticosteroid-induced osteopenia or osteoporosis who had been receiving corticosteroids for at least 6 months before study entry, therapy with risedronate sodium (5 mg daily for 1 year) was associated with a 2.7 or 1.9% increase in BMD at the lumbar spine or femoral neck, respectively, compared with placebo. A dosage of 2.5 daily of risedronate sodium was not substantially more effective than placebo in this study. When both risedronate dosage groups were combined, risedronate therapy also was associated with a decreased incidence of vertebral fractures relative to placebo.
Paget's Disease of Bone
Risedronate is used in the treatment of Paget's disease of bone (osteitis deformans).
Six months after initiation of therapy in a clinical study in men and women with moderate to severe Paget's disease of bone (serum alkaline phosphatase concentrations at least twice the upper limit of normal), normalization of serum alkaline phosphatase concentrations occurred in 77% of patients receiving risedronate sodium (30 mg daily for 2 months) and in 11% of those receiving etidronate disodium (400 mg daily for 6 months). At month 18 (16 and 12 months after discontinuance of risedronate and etidronate, respectively), 53% of those who had received risedronate remained in biochemical remission, compared with 14% of those treated with etidronate. Risedronate has been effective in a limited number of patients with refractory Paget's disease who had not responded to prior therapy with etidronate or calcitonin. Bone biopsies of non-Pagetic bone in patients with Paget's disease of bone treated with risedronate did not reveal evidence of osteomalacia, impairment of bone remodeling, or an appreciable decline in bone turnover.