Esophageal cancer, a meta-analysis concluded that bisphosphonate treatment is NOT associated with excess risk of esophageal cancer. General: infrequent cases of skin rash, rarely manifesting as Stevens–Johnson syndrome and toxic epidermal necrolysis, eye problems (uveitis, scleritis) and generalized muscle, joint, and bone pain (rarely severe) have been reported. In laboratory tests, decreased calcium and phosphate values may be seen but reflect expected action of the drug and are almost always not clinically relevant. Osteonecrosis of the jaw may occur while on this drug, if dental work of any kind is carried out. The risk is considerably higher for extractions in the mandible (lower jaw) than other areas of the mouth, and the risk increases if you have been taking it for four or more years  Although this side effect is uncommon (0.4-1.6% for oral alendronic acid), it occurs primarily in patients being administered intravenous bisphosphonates, with most cases being reported in cancer patients. Bone: alendronate has been linked in long-term users to the development of low-impact femoral fractures. Further, studies suggest that users of alendronate have an increase in the numbers of osteoclasts and develop giant, more multinucleated osteoclasts; the significance of this development is unclear. Fosamax has been linked to a rare type of leg fracture that cuts straight across the upper thigh bone after little or no trauma (subtrochanteric fractures). Interactions
Food and drugs containing large amounts of calcium, magnesium or aluminium (antacids) decrease the absorption of alendronate.
At least half an hour should pass after intake of alendronate before eating dairy products or taking the supplement or drug. Highly active vitamin D analogues or fluorides: no data is available. Concomitant treatment should be avoided. The additional beneficial effect of HRT (hormone replacement therapy) with estrogens/progestins or raloxifene in postmenopausal women with osteoporosis remains to be elucidated, but no interactions have been seen. The combination is therefore possible, but controversial. Intravenous ranitidine increases the oral bioavailability of alendronate. No clinical consequences are known. The combination of NSAIDs and alendronate may increase the risk of gastric ulcers. Both these drugs have the potential to irritate the upper gastro-intestinal mucosa. Pharmacology
Mechanism of action
Alendronate inhibits osteoclast-mediated bone-resorption. Like all bisphosphonates, it is chemically related to inorganic pyrophosphate, the endogenous regulator of bone turnover. But while pyrophosphate inhibits both osteoclastic bone resorption and the mineralization of the bone newly formed by osteoblasts, alendronate specifically inhibits bone resorption without any effect on mineralization at pharmacologically achievable doses. Its inhibition of bone-resorption is dose-dependent and approximately 1,000 times stronger than the equimolar effect of the first bisphosphonate drug, etidronate. Under therapy, normal bone tissue develops, and alendronate is deposited in the bone-matrix in a pharmacologically inactive form. For optimal action, enough calcium and vitamin D are needed in the body in order to promote normal bone development. Hypocalcemia should, therefore, be corrected before starting therapy. Etidronate has the same disadvantage as pyrophosphate in inhibiting mineralization, but all of the potent N-containing bisphosphonates, including alendronate, risedronate, ibandronate, and zoledronate, do not.