Alendronic acid, sold under the brand name Fosamax among others, is a
bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
used to treat
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
and
Paget's disease of bone
Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the ...
.
[ It is taken by mouth.][ Use is often recommended together with ]vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
, calcium supplementation
Calcium supplements are salts of calcium used in a number of conditions. Supplementation is generally only required when there is not enough calcium in the diet. By mouth they are used to treat and prevent low blood calcium, osteoporosis, and r ...
, and lifestyle changes.
Common side effects (1 to 10% of patients) include constipation, abdominal pain, nausea, and acid reflux
Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
.[ Use is not recommended during ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
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
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. In 2020, it was the 94th most commonly prescribed medication in the United States, with more than 7million prescriptions.
Medical uses
* Prevention and treatment of female osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
[
* Treatment of male osteoporosis
* Prevention and treatment of corticosteroid-associated osteoporosis together with supplements of calcium and vitamin D][
* Paget's disease][
]
Contraindications
Alendronate should not be used in:
* Acute inflammations of the gastrointestinal tract (esophagitis, gastritis, ulcerations)
* Clinically manifested osteomalacia
Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bone ...
* Certain malformations and malfunctions of the esophagus (strictures, achalasia)[
* Inability to stand, walk, or sit for 30 minutes after oral administration
* Renal impairment or chronic kidney disease as evidenced by a creatinine clearance below 30ml/min
* Hypersensitivity to alendronate or another ingredient in the product
* Hypocalcemia][
* Pregnancy and breastfeeding
* Patients below 18 yrs. of age, as no clinical data exists for this population
]
Side effects
* Gastrointestinal tract:
**Ulceration
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
and possible rupture of the esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
; this may require hospitalization and intensive treatment. Gastric and duodenal ulceration may also occur.
** Esophageal cancer
Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice ...
, 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
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...
and toxic epidermal necrolysis
Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later th ...
, eye problems (uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
, scleritis
Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as granulomatosis with polyangiitis or ...
) 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
Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws (the maxilla and the mandible). Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature.
Osteo ...
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
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
bisphosphonates, with most cases being reported in cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
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 osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
s 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
Estrogen or oestrogen is a category of sex steroid, sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogeny (biology), endogenous estrogens th ...
/progestins
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. Pr ...
or raloxifene
Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to ...
in postmenopausal women with osteoporosis remains to be elucidated, but no interactions have been seen. The combination is therefore possible, but controversial.
* Intravenous ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
increases the oral bioavailability of alendronate. No clinical consequences are known.
* The combination of NSAID
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s 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
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
-mediated bone-resorption. Like all bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
s, it is chemically related to inorganic pyrophosphate
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among other ...
, the endogenous regulator of bone turnover. But while pyrophosphate inhibits both osteoclastic bone resorption
Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.
The osteoclasts are multi-nucleated ...
and the mineralization of the bone newly formed by osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s, 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
Etidronic acid, also known as etidronate, is a bisphosphonate#non-nitrogenous, non-nitrogenous bisphosphonate used as a medication, detergent, water treatment, and cosmetic.
It was patented in 1966 and approved for medical use in 1977.
Use Me ...
. 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
Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mmol ...
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
Risedronic acid, often used as its sodium salt risedronate sodium, is a bisphosphonate. It slows down the cells which break down bone. It's used to treat or prevent osteoporosis, and treat Paget's disease of bone. It is taken by mouth.
It was pa ...
, ibandronate
Ibandronic acid is a bisphosphonate medication used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer. It may also be used to treat hypercalcemia (elevated blood calcium levels). ...
, and zoledronate
Zoledronic acid, also known as zoledronate and sold under the brand name Zometa by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due ...
, do not.
Pharmacokinetics
As with all potent bisphosphonates, the fraction of the drug that reaches the circulatory system intact (systemic bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
) 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.
References
External links
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{{Portal bar , Medicine
Bisphosphonates
Farnesyl pyrophosphate synthase inhibitors
Merck & Co. brands
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