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 preferred in men with osteoporosis. 
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. 
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. Alendronate demonstrated increased spine and femur bone mineral density in those with cystic fibrosis in an additional double-blinded trial.
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. 
Alendronate is not FDA-approved for use in growth hormone deficiency. A randomized controlled trial in osteoporotic adult-onset growth hormone deficiency demonstrated that 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 indicated to validate these results. 
Alendronate is not FDA-approved to treat hypercalcemia of malignancy. Previously, bisphosphonates were the mainstay of treatment, but intravenous calcitonin has demonstrated superior efficacy. Current clinical guidelines indicate first-line therapy is aggressive intravenous hydration, followed by calcitonin. Two to 4 days post calcitonin therapy initiation, zoledronic acid or ibandronate should be administered. Zoledronic acid is preferred over alendronate due to superior potency. If zoledronic acid is unavailable, ibandronate or pamidronate should be administered. 
Alendronate is frequently employed 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. 
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. 
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 contributes 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. 
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
Alendronate is a pregnancy Category C drug. It is unknown whether it is 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.
Use should be avoided in those taking human parathyroid hormone. It is recombinant due to the reduction in calcium-sparing effects, thus impacts serum calcium levels unfavorably.
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. 
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. 
Alendronate is contraindicated in 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. Alendronate should be avoided in patients with hypocalcemia. 
Baseline levels of Cr 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 concerning. The dose should be decreased or therapy discontinued if hypocalcemia is noted during therapy. Magnesium and phosphorus should be monitored at regularly occurring intervals. 
It is advised that some form of a drug-holiday be offered to patients on alendronate therapy. The accumulation of alendronate in the kidney allows for persistent anti-fracture benefits even after cessation of therapy. 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 should be noted that alendronate is an extremely safe drug, and the benefits of continued therapy often outweigh the benefits of a drug holiday. 
No known toxicities have been reported at this time.
Alendronate has no black box 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.