What are the guidelines for using risedronate (bisphosphonate) in postmenopausal women and older adults with osteoporosis, particularly those with a history of gastrointestinal disorders or impaired renal function?

Risedronate Use in Postmenopausal Women and Older Adults with Osteoporosis

Risedronate is indicated for treating postmenopausal osteoporosis with proven efficacy in reducing vertebral fractures, and should be administered as 35 mg once weekly (or 150 mg once monthly) taken at least 30 minutes before breakfast with plain water, with treatment duration limited to 3-5 years in most patients unless very high fracture risk persists. 1

Patient Selection and Indications

• Postmenopausal women with documented osteoporosis (T-score ≤ -2.5) or those with prior fragility fractures are appropriate candidates for risedronate therapy. 2, 1
• The American College of Physicians recommends bisphosphonates including risedronate as first-line pharmacologic treatment to reduce hip and vertebral fracture risk in postmenopausal women with known osteoporosis. 2
• For women with low bone mass (osteopenia, T-score -1.0 to -2.5), treatment decisions should incorporate additional risk factors such as age >65, family history of hip fracture, personal fragility fracture after age 50, or corticosteroid use >6 months. 2

Dosing Regimens and Administration

Standard Dosing Options

• Risedronate 35 mg once weekly is the preferred regimen, demonstrating equivalent efficacy to 5 mg daily dosing with improved convenience. 1, 3
• Risedronate 150 mg once monthly is an alternative option that shows non-inferior efficacy to daily dosing, with mean lumbar spine BMD increases of 3.5% at 1 year. 4, 5
• Both weekly and monthly regimens produce similar improvements in total hip, femoral neck, and trochanter BMD compared to daily dosing. 3, 6

Critical Administration Requirements

• Risedronate must be taken at least 30 minutes before the first food or drink of the day (other than plain water) with the patient remaining upright for at least 30 minutes to minimize esophageal irritation risk. 1
• Administer with 6-8 ounces of plain water only—no other beverages, food, or medications during this period. 1
• Patients must remain upright (sitting or standing) for at least 30 minutes after administration. 1

Special Populations and Contraindications

Gastrointestinal Disorders

• Risedronate demonstrates a favorable GI safety profile compared to other bisphosphonates, with endoscopically confirmed gastric ulcer incidence of only 4.1% versus 13.2% with alendronate. 7
• The incidence of upper GI adverse events with risedronate 35 mg weekly (approximately 16%) is similar to daily dosing and comparable to placebo. 1, 6
• For patients with severe swallowing difficulties or esophageal disorders who cannot tolerate oral bisphosphonates, switch to intravenous zoledronic acid (5 mg annually or 4 mg every 6 months) which bypasses the GI tract entirely. 8

Renal Impairment

• Risedronate is not recommended for patients with severe renal impairment (creatinine clearance <30 mL/min) due to lack of clinical experience. 1
• For patients with creatinine clearance <60 mL/min, consider switching to denosumab as an alternative, which does not require renal dose adjustment. 9
• No dose adjustment is needed for mild to moderate renal impairment (CrCl ≥30 mL/min). 1

Treatment Duration and Monitoring

Standard Treatment Duration

• The FDA label and American College of Physicians strongly recommend treating for 5 years as the standard duration, with periodic reassessment of fracture risk. 1, 2
• All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. 1
• Patients at low risk for fracture should be considered for drug discontinuation after 3-5 years of use. 1, 9

Risk Stratification for Continuation Beyond 5 Years

• Continue treatment beyond 5 years only for patients with very high ongoing fracture risk: 9

  • Previous hip or vertebral fractures during treatment
  • Multiple non-spine fractures
  • Hip BMD T-score ≤ -2.5 despite treatment
  • Age >80 years
  • Ongoing high-dose glucocorticoid use (≥7.5 mg prednisone daily)

• For patients without these high-risk features, initiate a drug holiday after 5 years with periodic reassessment. 9

Monitoring Requirements

• The American College of Physicians recommends against routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases. 9
• Ensure adequate calcium supplementation (1000-1200 mg/day) and vitamin D (800 IU/day) throughout treatment. 9, 1
• Monitor for clinical fractures and changes in fracture risk profile during treatment. 9

Efficacy Data

Fracture Risk Reduction

• Risedronate reduces vertebral fracture risk by 62% radiographically and 69% clinically within the first year of treatment in postmenopausal women with osteoporosis. 7
• After 3 years of treatment, risedronate reduces relative risk of femoral neck fracture by 40%, or by 60% in women with osteoporosis and prevalent vertebral fractures. 7
• The fracture reduction benefit remains significant even after 5 years of continuous treatment (50% reduction in vertebral fractures). 7

Bone Mineral Density Improvements

• Mean lumbar spine BMD increases by 3.4-4.25% at 12 months with risedronate treatment. 4, 3
• Decreases in biochemical markers of bone turnover occur as early as 1 month, reaching maximum effect at 3-6 months. 7

Safety Profile and Adverse Events

Common Adverse Events

• The overall incidence of adverse events is similar between risedronate and placebo, with gastrointestinal complaints (diarrhea, abdominal pain, constipation) being most common at 5-9% incidence. 1
• Acute phase reactions (flu-like symptoms) occur in approximately 2.3% of patients with once-weekly dosing, typically within 3 days of first dose and lasting ≤7 days. 1
• The withdrawal rate due to adverse events is low at 8-9%, comparable to placebo. 1, 4

Serious Long-Term Risks

• Osteonecrosis of the jaw (ONJ) is rare with osteoporosis dosing at <1 case per 100,000 person-years, but risk increases with duration beyond 5 years. 9, 1
• Complete dental evaluation and necessary dental work before initiating bisphosphonate therapy to minimize ONJ risk. 1, 9
• Atypical femoral fractures occur at 3.0-9.8 cases per 100,000 patient-years, with risk increasing significantly after 5 years and especially beyond 8 years of continuous use. 9, 1
• Patients presenting with thigh or groin pain should be evaluated for incomplete femur fracture, and the contralateral limb should be assessed. 1

Musculoskeletal Pain

• Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in postmarketing experience, with onset ranging from one day to several months after starting treatment. 1
• Most patients experience symptom relief after stopping medication, though some have recurrence upon rechallenge. 1
• Consider discontinuing risedronate if severe musculoskeletal symptoms develop. 1

Special Clinical Situations

Cancer Treatment-Induced Bone Loss

• For premenopausal women on ovarian suppression with aromatase inhibitors, risedronate 35 mg weekly effectively prevents rapid bone loss associated with treatment. 2
• In postmenopausal women receiving aromatase inhibitors with T-score <-2.0 or two or more clinical risk factors for fracture, anti-resorptive therapy including risedronate is recommended. 2
• Bisphosphonates should be continued for the duration of endocrine treatment or up to 5 years, whichever is shorter. 9

Glucocorticoid-Induced Osteoporosis

• Risedronate reduces vertebral fracture risk by 70% in the first year among patients on long-term glucocorticoid therapy (≥7.5 mg prednisone equivalent for >3 months). 7
• Prevention and treatment should be initiated regardless of age or gender when glucocorticoid therapy is expected to exceed 3 months. 7

Critical Pitfalls to Avoid

• Never administer risedronate with food, beverages other than plain water, or other medications—this dramatically reduces absorption and efficacy. 1
• Do not allow patients to lie down for at least 30 minutes after taking risedronate—this increases esophageal irritation risk. 1
• Do not automatically continue treatment beyond 5 years without reassessing fracture risk—this exposes patients to increasing risk of ONJ and atypical femoral fractures without proven additional benefit in low-risk individuals. 9, 1
• Do not use risedronate in patients with severe renal impairment (CrCl <30 mL/min)—switch to denosumab instead. 1, 9
• Do not forget to ensure adequate vitamin D and calcium supplementation—vitamin D deficiency should be corrected before initiating bisphosphonate therapy to prevent hypocalcemia. 9, 1