Fosamax Post-Bariatric Surgery Use: What Clinicians and Patients Need to Know

Does alendronate work after bariatric surgery?

No study cited on this page measured alendronate absorption, bone density change or fracture rates specifically in people who have had bariatric surgery. The practical question therefore comes down to two things the label does address: how much of an oral dose reaches the bloodstream, and whether the upper gut can tolerate the tablet.

Alendronate is a bisphosphonate. It binds to bone hydroxyapatite and inhibits osteoclast activity, the cells that resorb bone, without interfering with osteoclast recruitment or attachment; bone turnover falls and bone formation exceeds resorption at remodeling sites, so bone mass rises [1]. Alendronate already incorporated into bone matrix is not pharmacologically active and is released slowly as bone remodels [1].

What happens to bone after bariatric surgery

A review of bariatric surgery and bone concluded that loss of bone mass frequently occurs after these operations, and that proposed contributors include nutritional deficiencies, rapid weight loss itself, fat-derived adipokines and gut-derived appetite-regulating hormones; the relative role of each is not fully defined [5].

A Swedish retrospective cohort followed 38,971 people who had gastric bypass and an equal number of propensity-score-matched controls. Over a median follow-up of 3.1 years, gastric bypass was associated with an increased risk of any fracture, with a hazard ratio of 1.32 (95% CI, 1.18 to 1.47) in patients without diabetes and 1.26 (95% CI, 1.05 to 1.53) in those with diabetes. The risk appeared to increase with time [4]. Fall injury without fracture was also increased, while the degree of weight loss and calcium and vitamin D supplementation at one year were not associated with increased fracture risk [4].

How much of an oral dose is absorbed?

Very little, even with an intact gut and ideal technique. Oral bioavailability is about 0.64% in women and 0.59% in men after an overnight fast, with the dose taken two hours before a standardized breakfast [1].

The label's own food and drink studies show how easily that number moves:

• Taking alendronate with coffee or orange juice reduced bioavailability by about 60% [1].
• Bioavailability was negligible when it was taken with, or up to two hours after, a standardized breakfast [1].
• Dosing 0.5 or 1 hour before breakfast reduced bioavailability by about 40% compared with dosing two hours before eating [1].

Alendronate was nevertheless effective in trials that used dosing at least 30 minutes before breakfast [1].

The dosing rules the label sets

The Fosamax label says to take the tablet on arising for the day, with plain water only, at least one-half hour (30 minutes) before the first food, beverage or medication of the day [1]. It says to swallow the tablet whole with a full glass of 6 to 8 ounces of water, and not to lie down for at least 30 minutes and until after the first food of the day [1]. The label says not to take it at bedtime or before arising, and notes that other beverages including mineral water, food and some medications reduce absorption [1]. It states that not following the instructions may increase the risk of esophageal adverse experiences [1].

Calcium supplements, antacids and other oral products containing multivalent cations interfere with absorption, and the label says to wait at least one-half hour after alendronate before any other oral medication [1]. For a missed weekly dose, the label says to take one dose the morning after remembering, never two doses on the same day, then return to the usual chosen day [1].

Esophageal risk and the label's contraindications

Alendronate can cause local irritation of the upper gastrointestinal mucosa [1]. Esophagitis, esophageal ulcers and erosions, occasionally with bleeding and rarely followed by stricture or perforation, have been reported, some severe enough to require hospitalization [1]. The label says the risk of severe esophageal events appears greater in patients who lie down after dosing, who do not swallow the tablet with the full 6 to 8 ounces of water, or who keep taking it after symptoms start [1].

The label says patients should stop alendronate and seek medical attention for difficulty or pain on swallowing, retrosternal pain, or new or worsening heartburn [1]. It advises caution in patients with active upper gastrointestinal problems such as Barrett's esophagus, dysphagia, gastritis, duodenitis or ulcers [1].

The label lists these contraindications: esophageal abnormalities that delay emptying, such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; hypocalcemia; and hypersensitivity to a component [1].

Calcium, vitamin D and kidney function

The label says hypocalcemia must be corrected before alendronate is started, and that other disorders affecting mineral metabolism, such as vitamin D deficiency, should also be effectively treated [1]. It says to take supplemental calcium if dietary intake is inadequate, and that patients at risk of vitamin D insufficiency (those over 70, nursing-home bound or chronically ill) may need vitamin D [1].

According to the label, alendronate is not recommended when creatinine clearance is below 35 mL/min, no dose change is needed between 35 and 60 mL/min, and no adjustment is needed for liver impairment because the drug is not metabolized [1].

Options that bypass the gut

Zoledronic acid is given as a single 15-minute intravenous infusion once a year. In a trial of 3,889 women assigned to zoledronic acid 5 mg and 3,876 to placebo, with infusions at baseline, 12 and 24 months, treatment reduced morphometric vertebral fractures by 70% (3.3% vs 10.9%) and hip fractures by 41% (1.4% vs 2.5%) over three years; nonvertebral fractures fell 25% and clinical vertebral fractures 77% [2]. Serious atrial fibrillation occurred more often with zoledronic acid (50 vs 20 patients) [2].

Denosumab is given as 60 mg subcutaneously every six months. In the FREEDOM trial of 7,868 women with osteoporosis, 36 months of treatment reduced new radiographic vertebral fractures by 68% (2.3% vs 7.2%), hip fractures by 40% (0.7% vs 1.2%) and nonvertebral fractures by 20% (6.5% vs 8.0%) [3].

In these trials, zoledronic acid and denosumab reduced fractures in women with osteoporosis [2][3].

Long-term use and the rare risks, in brief

The label states that the optimal duration of use has not been determined, that its efficacy and safety data come from four years, and that patients at low risk of fracture should be considered for drug discontinuation after 3 to 5 years [1]. The ASBMR task force suggests that after five years of oral bisphosphonate therapy, reassessment of risk should be considered [6].

Osteonecrosis of the jaw has been reported with bisphosphonates including Fosamax. An international consensus review estimated its incidence at 0.001% to 0.01% in osteoporosis patients, versus 1% to 15% in cancer patients on high-dose, frequent parenteral therapy [1][7]. Atypical femur fractures are also rare: the ASBMR task force put the absolute risk at 3.2 to 50 cases per 100,000 person-years, up to about 100 per 100,000 person-years with long-term use [8]. The label says anyone with bisphosphonate exposure and new thigh or groin pain should be evaluated to rule out an incomplete femur fracture [1].

What to watch for

The most common adverse reactions, at 3% or more, are abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain and nausea [1]. Severe and occasionally incapacitating bone, joint or muscle pain has been reported after marketing, with onset from one day to several months, and the label says to discontinue if symptoms are severe [1].