Risedronate sodium is used for the prevention and treatment of postmenopausal osteoporosis; the drug also is used in men with osteoporosis to increase bone mass.
In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), experts recommend that pharmacologic therapy for osteoporosis be considered in postmenopausal women and in men 50 years of age or older who are at high risk of fractures (generally those who have experienced a previous hip or vertebral fracture or who have low bone mineral density [BMD]); pharmacologic therapy also may be considered in postmenopausal women and in men 50 years of age or older who have low bone mass, although there is less evidence supporting overall fracture risk reduction in such patients. When selecting an appropriate pharmacologic agent, use of a drug with proven antifracture efficacy is recommended. Available options include bisphosphonates (e.g., alendronate, risedronate, zoledronic acid, ibandronate), denosumab, raloxifene, calcitonin, or teriparatide with varying levels of recommendation given in expert guidelines based on the available evidence supporting fracture risk reduction for each drug. Choice of therapy should be individualized based on the potential benefits and adverse effects of therapy as well as patient preferences, comorbidities, and risk factors. For additional information on the prevention and treatment of osteoporosis,
Prevention in Postmenopausal Women
Risedronate is used for the prevention of osteoporosis in postmenopausal women. Risk factors for postmenopausal osteoporosis and related fractures include early menopause, advanced age, low BMD, low body mass index (BMI), previous fracture or family history of fracture/osteoporosis, excessive alcohol intake, smoking, inadequate physical activity, low calcium and vitamin D intake, certain drugs (e.g., glucocorticoids), and medical conditions or diseases (e.g., rheumatoid arthritis, diabetes mellitus, Cushing syndrome, hyperparathyroidism).
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 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 (as immediate-release tablets) produced increases in lumbar spine and hip BMD similar to those observed with a dosage of 5 mg daily.
In a 1-year double-blind, active-controlled study, risedronate sodium 35 mg once weekly (as delayed-release tablets) was found to be noninferior to a dosage of 5 mg daily (as immediate-release tablets) with respect to mean change in BMD from baseline.
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 sodium 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 is used for the prevention and treatment of glucocorticoid-induced osteoporosis. The manufacturer recommends use of risedronate in men and women who are either initiating or continuing systemic glucocorticoid therapy for chronic disease in a daily dosage equivalent to at least 7.5 mg of prednisone.
The American College of Rheumatology (ACR) recommends optimizing calcium and vitamin D intake and lifestyle modifications (e.g., diet, smoking cessation, weight-bearing or resistance-training exercise) in all patients receiving long-term glucocorticoid therapy; in addition, pharmacologic therapy with an oral bisphosphonate is recommended in patients who are considered to be at moderate-to-high risk of fracture. Oral bisphosphonates generally are preferred because of their demonstrated antifracture benefits as well as their safety and low cost; other options include IV bisphosphonates, teriparatide, denosumab, and raloxifene (for postmenopausal women if no other therapy is appropriate). For additional information on the use of bisphosphonates for prevention and treatment of glucocorticoid-induced osteoporosis,
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 glucocorticoid 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.
In patients with glucocorticoid-induced osteopenia or osteoporosis who had been receiving glucocorticoids 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 Disease of Bone
Risedronate is used in the treatment of Paget disease of bone (osteitis deformans).
Six months after initiation of therapy in a clinical study in men and women with moderate to severe Paget 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 disease who had not responded to prior therapy with etidronate or calcitonin. Bone biopsies of non-Pagetic bone in patients with Paget disease of bone treated with risedronate did not reveal evidence of osteomalacia, impairment of bone remodeling, or an appreciable decline in bone turnover.