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Continuing Education Activity

Alendronate is FDA-approved for the treatment of postmenopausal osteoporosis, prevention of postmenopausal osteoporosis, steroid-induced osteoporosis, male osteoporosis, and Paget disease of the bone. This activity reviews the indications, target patient, administration, adverse effects, mechanism of action, and monitoring of alendronate as part of an interprofessional strategy.


  • Identify the target patient population, mechanism of action, and proper administration of alendronate.
  • Describe the adverse effects and contraindications of alendronate.
  • Review appropriate monitoring for alendronate therapy.
  • Summarize the interprofessional team strategies for improving care coordination and communication to advance alendronate, and improve outcomes in indicated conditions.


Alendronate is FDA-approved for the treatment of postmenopausal osteoporosis, prevention of postmenopausal osteoporosis, steroid-induced osteoporosis, male osteoporosis, and Paget disease of the bone. Alendronate is an option for maintaining or increasing bone-mass, although risedronate is the preferred agent in men with osteoporosis.[1]

Alendronate is not FDA-approved for use in Crohn-induced osteoporosis. Studies have evaluated the optimal treatment of Crohn-induced osteoporosis with evidence indicating the use of pamidronate infusions to avoid upper gastrointestinal (GI) adverse effects associated with oral alendronate. However, current evidence supports bisphosphonates as first-line therapy, administered orally, or parenterally.[2]

Alendronate is not FDA-approved for use in osteopenia secondary to cystic fibrosis of the lung. A multicenter, randomized controlled trial with 56 participants conducted in Canada indicated alendronate therapy was well tolerated and improved bone mineral density over 12 months when compared to placebo.[3] Alendronate demonstrated increased spine and femur bone mineral density in those with cystic fibrosis in an additional double-blinded trial.[4] 

Alendronate is not FDA-approved for use in fibrous dysplasia of the bone. Current data endorses the use of pamidronate in decreased bone remodeling measured through decreased serum alkaline phosphatase and urinary hydroxyproline, but no current studies support alendronate use.[5]

Alendronate is not FDA-approved for use in growth hormone deficiency. A randomized controlled trial in osteoporotic adult-onset growth hormone deficiency demonstrated that the addition of alendronate therapy for 12 months provided no significant difference in bone turnover, bone mineral density, or prevalence of vertebral fractures. However, participants maintained on recombinant growth hormone in addition to alendronate indicated a significant decrease in bone turnover and an increase in bone mineral density of the lumbar spine. Further study is necessary to validate these results.[6]

Alendronate is not FDA-approved to treat hypercalcemia of malignancy. Previously, bisphosphonates were the mainstay of treatment, but intravenous calcitonin has demonstrated superior efficacy.[7] Current clinical guidelines indicate first-line therapy is aggressive intravenous hydration, followed by calcitonin. Two to four days post calcitonin therapy initiation, administer zoledronic acid, or ibandronate. Zoledronic acid is preferable to alendronate due to superior potency. If zoledronic acid is unavailable, ibandronate or pamidronate are other options.[8]

Clinicians frequently employ alendronate in the treatment of male hypogonadism induced osteoporosis. A randomized controlled study of 22 osteoporotic men with long-standing hypogonadism demonstrated that femoral neck bone mineral density increased with long-term administration of alendronate along with testosterone replacement.[9]

Rarely, alendronate is used off-label in pediatric populations with bone necrosis, hypervitaminosis D, and secondary amenorrhea. Due to the unknown teratogenic effect and the long half-life of bisphosphonates, there is not sufficient evidence to support bisphosphonate therapy in pediatric populations.[10]

Mechanism of Action

Alendronate is a bisphosphonate. Binding to hydroxyapatite crystals present in bone downregulates osteoclast-mediated bone reabsorption and decreases bone matrix breakdown. Both of these mechanisms contribute to regulating mineral reabsorption and turnover. Alendronate differs from other bone-modifying supplements as it suppresses bone formation, but it does not modify bone mineral accrual in endocortical or intracortical bone.[11]

  • Pharmacokinetics:
    • 0.64% bioavailability in fasting women, 0.59% bioavailability in fasting men; bioavailability is reduced by up to 60% with food
    • Half-life: approximately 10 years in bone (terminal)
    • Excretion: Urine 50%, feces (unabsorbed drug)


Alendronate is available in 5 mg, 10 mg, 35 mg, 40 mg, or 70 mg oral tablets; 70 mg tablet for solution; and 70 mg/75 mL oral solution.

Clinical indication directs dosing guidelines

  • Postmenopausal women: 5 mg oral tablet daily or 35 mg oral tablet once weekly
  • Glucocorticoid-induced osteoporosis: 5 mg oral tablet once daily or 10 mg oral tablet once daily in women not undergoing hormone replacement therapy
  • Paget disease of the bone: 40 mg/day oral tablet for six months
  • Pediatric patients: Safety and efficacy have not been established
  • Severe renal impairment: Dosing not recommended; seek alternative treatment
  • Low-risk of fracture: Consider drug discontinuation after 3 to 5 years of use.

Alendronate was a pregnancy Category C drug under the prior FDA classification system. It is unknown whether alendronate gets excreted in the milk of women who are lactating, use with caution.

Alendronate should be taken in the morning with a full glass of water on an empty stomach in an upright position. Individuals should remain in an upright position for 30 minutes after intake to decrease the risk of adverse reactions. Do not chew, suck, or crush the tablet.

Patients taking human parathyroid hormone should avoid taking alendronate. This combination can reduce calcium-sparing effects, thus impacts serum calcium concentrations unfavorably. 

Adverse Effects

The most common adverse events include transient hypocalcemia, transient hypophosphatemia, and GI symptoms (e.g., abdominal pain, heartburn, nausea, constipation, diarrhea, flatulence, and esophagitis). Additional adverse events are myalgia, joint pain, headache, dizziness, peripheral edema, back pain, and weakness.

Rare but reported adverse events include toxic epidermal necrosis and oropharyngeal ulceration.[12]

Post-marketing reports include rare occurrences of osteonecrosis of the jaw, generally associated with tooth extraction or local infection with delayed healing; esophageal erosions/esophagitis/esophageal ulcers; and hypersensitivity reactions.[13]


Contraindications to alendronate include patients with known hypersensitivity, esophageal abnormalities, delayed esophageal emptying, or achalasia. Severe risk of esophageal morbidity indicates avoidance in patients who are unable to sit or stand upright for at least 30 minutes. Avoid alendronate in patients with hypocalcemia.[12]


Baseline concentrations of calcium and bone mineral density should be established before therapy begins, with follow-up testing at 6 to 12 months post-therapy. Calcium at baseline and continual monitoring is needed if hypocalcemia risk is recurring. The clinician should decrease the dose or discontinue therapy if hypocalcemia occurs during treatment. Magnesium and phosphorus require monitoring at regular intervals.[14]

The physician should offer some form of a drug-holiday to patients on alendronate therapy. The accumulation of alendronate in the kidney allows for persistent anti-fracture benefits even after cessation of treatment. Current recommendations suggest tailoring the drug holiday length to the individual patients. The average drug-holiday in low-risk patients is 3 to 5 years. It also bears mention that alendronate is an extremely safe drug, and the benefits of continued therapy often outweigh the benefits of a drug holiday.[15]


There are no known toxicities reported at this time.

Alendronate has no FDA boxed warning.

Some post-marketing reports indicated an association with significant esophageal and gastric mucosal toxicity; however, studies have since concluded alendronate does not cause predictable mucosal damage when used as directed.[16]

Enhancing Healthcare Team Outcomes

Alendronate is a frequently used agent to manage osteoporosis and several other bone disorders, often prescribed in combination with vitamin D. Besides the physician, the nurse and pharmacist must be fully aware of the therapeutic uses and adverse reactions of this agent. The most feared complication is osteonecrosis of the jaw, which is most likely to occur when there has been dental work carried out. Thus, the patient must receive education about this drug and the need to see a healthcare provider before any oral cavity procedure. Also, the pharmacist should educate the patient on potential drug interactions with alendronate, and perform an overall medication reconciliation to check for drug interactions, reporting any concerns to the physician and nurse. All patients on alendronate need to be closely monitored for side effects, which can be serious; this is where the nurse needs to monitor the drug and counsel the patient, and make a direct inquiry about potential adverse effects, and notify the healthcare team of any issues.[17] Alendronate therapy requires interprofessional teamwork and coordination to ensure optimal patient outcomes. [Level V]

Article Details

Article Author

Lyndie Wilkins Parker

Article Editor:

Charles Preuss


8/31/2021 10:29:27 AM

PubMed Link:




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