What are the side effects of alendronate?

Alendronate Side Effects

Alendronate can cause serious esophageal problems, low blood calcium, severe bone/joint/muscle pain, jaw bone necrosis (osteonecrosis), and unusual thigh bone fractures, with risks increasing significantly after 5 years of continuous use. 1

Serious Long-Term Adverse Events

Esophageal Problems

• Esophageal irritation, inflammation, or ulcers (which may bleed) are the most critical immediate risks requiring strict administration protocols 1
• Must take with a full glass of plain water (6-8 oz), remain upright for at least 30 minutes, and avoid all food/drink during this period 1
• Stop alendronate immediately if chest pain, new or worsening heartburn, or trouble/pain swallowing develops 1
• Gastric and duodenal ulcers have been reported in post-marketing surveillance, though controlled trials showed no increased risk versus placebo 2

Hypocalcemia (Low Blood Calcium)

• Alendronate may lower blood calcium levels, particularly dangerous if pre-existing hypocalcemia exists 1
• Symptoms include muscle spasms, twitches, cramps, numbness or tingling in fingers/toes/around mouth 1
• Vitamin D deficiency must be corrected before initiating therapy, as deficiency attenuates efficacy and increases hypocalcemia risk, particularly with IV formulations 3
• Calcium (1,000-1,500 mg/day) and vitamin D (400-800 IU/day) supplementation is required throughout treatment 2

Osteonecrosis of the Jaw (ONJ)

• Incidence is very rare at <1 case per 100,000 person-years with osteoporosis dosing, but risk increases significantly with duration beyond 5 years 3, 1
• Recent dental surgery or tooth extraction is the most consistent risk factor 3
• Complete all necessary dental work before initiating bisphosphonate therapy 3
• Dental examination should be performed before starting alendronate 1

Atypical Femoral Fractures

• Incidence ranges from 3.0 to 9.8 cases per 100,000 patient-years, with risk beginning to increase significantly after 5 years of treatment 3
• Risk escalates sharply beyond 8 years of continuous use, increasing from 1.78 per 100,000 person-years to 113 per 100,000 person-years 3
• Asian patients face up to 8 times higher risk than White patients (595 versus 109 per 100,000 person-years) 3
• Symptoms include new or unusual pain in hip, groin, or thigh 1
• If atypical femur fracture occurs, stopping bisphosphonates reduces contralateral fracture risk (otherwise 25%) 3

Severe Bone, Joint, or Muscle Pain

• Some patients develop severe bone, joint, or muscle pain requiring discontinuation 1
• This differs from the common transient musculoskeletal pain seen in many patients 4

Common Adverse Events

Gastrointestinal Effects

• Most common side effects include abdominal pain, heartburn, constipation, diarrhea, upset stomach, and nausea 1
• Dyspepsia and abdominal pain are generally transient 2
• No statistically significant differences between alendronate 10 mg/day and placebo in upper GI adverse events were found in large clinical trials 4
• Upper GI adverse events tend to be transient and associated with improper administration 4

Other Adverse Reactions

• Allergic reactions including hives or swelling of face, lips, tongue, or throat may occur 1
• Worsening of asthma has been reported 1

Rare Renal Complications

• Nephrotic syndrome has been reported after alendronate administration, with proteinuria resolving 40 days after discontinuation without specific treatment 5
• Alendronate should not be used in patients with creatinine clearance <35 mL/min 3

Optimal Treatment Duration to Minimize Risks

• The American College of Physicians strongly recommends 5 years as the standard treatment duration to balance benefits and risks 3
• Evidence shows that increasing duration beyond 5 years probably reduces vertebral fractures but not other fractures, while increasing long-term harm risk 3
• An estimated 162 osteoporosis-related fractures are prevented for every one atypical femoral fracture associated with antiresorptive medication treatment 3

Critical Contraindications

• Do not use if: esophageal problems exist, cannot stand/sit upright for 30 minutes, hypocalcemia is present, or allergy to alendronate exists 1
• Cannot chew or suck on tablets—must swallow whole 1
• Do not take with mineral water, coffee, tea, soda, or juice—only plain water 1

Special Population Warnings

• Not for use in children 1
• Pregnancy risk unknown; breastfeeding safety unknown 1
• Patients with kidney problems, malabsorption syndrome, or planned dental surgery require special consideration 1