Alendronic acid
Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes. Common side effects (1 to 10% of patients) include constipation, abdominal pain, nausea, and acid reflux. Use is not recommended during pregnancy or in those with poor kidney function. Alendronic acid works by decreasing the activity of cells that break down bone. Alendronic acid was first described in 1978 and approved for medical use in the  United States in 1995. It is available as a generic medication. In 2019, it was the 96th most commonly prescribed medication in the United States, with more than 7million prescriptions. Contraindications. Alendronate should not be used in: 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. Pharmacokinetics. As with all potent bisphosphonates, the fraction of the  drug that reaches the circulatory system intact (systemic bioavailability) after oral dosing is low, averaging only 0.6–0.7% in women and in men under fasting conditions. Intake together with meals and beverages other than water further reduces the bioavailability. The absorbed drug rapidly partitions, with approximately 50% binding to the exposed bone surface; the remainder is excreted unchanged by the kidneys. Unlike with most drugs, the strong negative charge on the two phosphonate moieties limits oral bioavailability, and, in turn, the exposure to tissues other than bone is very low. After absorption in the bone, alendronate has an estimated terminal elimination  half-life of 10 years.