What is the recommended use and dosage of risedronate (bisphosphonate) for treating osteoporosis?

Risedronate for Osteoporosis: Recommended Use and Dosing

Risedronate is a first-line bisphosphonate for treating osteoporosis in both postmenopausal women and men, with standard dosing of 35 mg once weekly or 5 mg daily for treatment, and 35 mg weekly or 5 mg daily for prevention in postmenopausal women. 1, 2

Approved Dosing Regimens

Treatment of Established Osteoporosis

• 35 mg once weekly (standard treatment dose) 1
• 5 mg daily (alternative daily dosing) 1
• 75 mg on two consecutive days per month 1
• 150 mg once monthly 1
• 35 mg once weekly delayed-release formulation (Atelvia) for treatment only 1

Prevention of Osteoporosis in Postmenopausal Women

• 35 mg once weekly or 5 mg daily 1

Clinical Indications and Patient Selection

Postmenopausal Women

Bisphosphonates, including risedronate, are recommended as first-line therapy for postmenopausal osteoporosis, with selection based on patient preference. 1

Treatment is indicated for:

• Women with T-score ≤ -2.5 1
• Women with T-score between -1.0 and -2.5 who have 10-year risk of major osteoporotic fracture ≥20% or hip fracture risk ≥3% by FRAX 1
• Women with low-trauma fracture, even without osteoporosis on DEXA 1

For osteopenic women ≥65 years with advanced osteopenia (T-score approaching -2.5), risedronate reduces fragility fracture risk by 73% compared to placebo, similar to reductions seen in osteoporotic women. 1

Men with Osteoporosis

Risedronate monotherapy significantly improves bone mineral density in men with osteoporosis: lumbar spine by 4.39% (95% CI 3.46-5.31), total hip by 2.46% (95% CI 1.71-3.22), and femoral neck by 1.95% (95% CI 0.62-3.27). 1

Oral bisphosphonates like risedronate should be recommended as first-line therapy for men with osteoporosis, with intravenous bisphosphonates as second-line. 1

Special Populations

Glucocorticoid-Induced Osteoporosis

• Risedronate 5 mg daily is approved for both prevention and treatment of glucocorticoid-induced osteoporosis 3
• Indicated for adults ≥30 years receiving very high-dose glucocorticoids (prednisone ≥30 mg/day with cumulative dose >5 gm in 1 year) 1
• Treatment should be considered for patients on long-term glucocorticoids (≥3-6 months) 1

Cancer Treatment-Induced Bone Loss

• Risedronate prevents bone loss in premenopausal women with chemotherapy-induced menopause, though one trial showed no significant difference in lumbar spine BMD at 1 year 1
• Effective in women undergoing ovarian suppression or with treatment-induced ovarian failure 1

Key Contraindications and Precautions

Absolute Contraindications

• Abnormalities of the esophagus 1, 2
• Inability to stand or sit upright for at least 30 minutes 1, 2
• Hypocalcemia (must be corrected before initiating therapy) 1, 2
• Severe renal impairment (creatinine clearance <30 mL/min) - not recommended due to lack of clinical experience 2

Important Warnings

Osteonecrosis of the Jaw (ONJ)

• Risk increases with duration of bisphosphonate exposure 2
• Patients should have dental examination with preventive dentistry before starting therapy if risk factors present 2
• Consider discontinuation based on individual benefit/risk assessment if ONJ develops 2

Atypical Femoral Fractures

• Low-energy fractures of the femoral shaft can occur with bisphosphonate therapy 2
• Patients may report prodromal dull, aching thigh pain weeks to months before complete fracture 2
• Evaluate contralateral limb if atypical fracture occurs 2
• Consider interruption of therapy pending individual risk/benefit assessment 2

Musculoskeletal Pain

• Severe and occasionally incapacitating bone, joint, and/or muscle pain reported in postmarketing experience 2
• Time to onset varies from one day to several months 2
• Consider discontinuing if severe symptoms develop 2

Duration of Therapy

There appears to be a trend toward interrupting bisphosphonate therapy after 5 to 10 years, though the optimal duration remains uncertain. 1

Efficacy Data

Fracture Reduction in Postmenopausal Women

• Vertebral fracture incidence reduced by 49-65% after 1-3 years in women with established osteoporosis 4, 5, 6
• Non-vertebral fracture risk reduced by up to 39% over 3 years 6
• Hip fracture risk reduced by 40% in elderly women with low hip BMD and clinical risk factors, and by 60% in women with prevalent vertebral fracture 6

BMD Improvements

• Lumbar spine BMD increases by 4.49% at 24 months in late-postmenopausal women with osteopenia 7
• Significant improvements in femoral neck and total hip BMD 1, 4, 7

Administration Guidelines

• Risedronate immediate-release must be taken at least 30 minutes before the first food or drink of the day (other than water) 2
• Risedronate delayed-release (Atelvia) should be taken immediately following breakfast 1, 2
• Patient must remain upright (sitting or standing) for at least 30 minutes after administration 2
• Swallow tablet whole with plain water (6-8 oz); do not chew or suck 2

Supplementation

All patients should receive adequate calcium (1000-1200 mg/day) and vitamin D (600-800 IU/day, serum level ≥20 ng/mL) supplementation. 1, 2

Common Pitfalls to Avoid

• Do not administer to patients with creatinine clearance <30 mL/min 2
• Do not use in patients unable to comply with upright positioning requirements - this increases risk of esophageal adverse events 1, 2
• Avoid administering delayed-release formulation before breakfast under fasting conditions - this significantly increases abdominal pain incidence 2
• Do not use combination bisphosphonate therapy - not recommended 1
• Ensure hypocalcemia is corrected before initiating therapy 2