Alendronic acid

Last updated
Alendronic acid
Alendronic acid.svg
Alendronate-3D-balls.png
Clinical data
Trade names Fosamax, Binosto, others
Other namesAlendronate, alendronate sodium
AHFS/Drugs.com Monograph
MedlinePlus a601011
License data
Pregnancy
category
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 0.6%
Metabolism excreted unchanged
Elimination half-life 126 months
Excretion Kidney
Identifiers
  • sodium [4-amino-1-hydroxy-1-(hydroxy-oxido-phosphoryl)- butyl]phosphonic acid trihydrate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.128.415 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C4H13NO7P2
Molar mass 249.096 g·mol−1
3D model (JSmol)
  • O=P(O)(O)C(O)(CCCN)P(=O)(O)O
  • InChI=1S/C4H13NO7P2/c5-3-1-2-4(6,13(7,8)9)14(10,11)12/h6H,1-3,5H2,(H2,7,8,9)(H2,10,11,12) Yes check.svgY
  • Key:OGSPWJRAVKPPFI-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. [2] It is taken by mouth. [2] Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes. [2]

Contents

Common side effects (1 to 10% of patients) include constipation, abdominal pain, nausea, and acid reflux. [2] Use is not recommended during pregnancy or in those with poor kidney function. [3] Alendronic acid works by decreasing the activity of cells that break down bone. [2]

Alendronic acid was first described in 1978 and approved for medical use in the United States in 1995. [2] [4] It is available as a generic medication. In 2020, it was the 94th most commonly prescribed medication in the United States, with more than 7 million prescriptions. [5] [6]

Medical uses

Alendronic acid 35 mg (as alendronate sodium 45.7 mg) oral tablet 003783568lg Alendronic acid 35 MG (as alendronate sodium 45.7 MG) Oral Tablet.jpg
Alendronic acid 35 mg (as alendronate sodium 45.7 mg) oral tablet

Contraindications

Alendronate should not be used in:

Side effects

Interactions

Pharmacology

Mechanism of action

Relative potency [16]
BisphosphonateRelative potency
Etidronate 1
Tiludronate 10
Pamidronate 100
Alendronate100-500
Ibandronate 500-1000
Risedronate 1000
Zoledronate 5000

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. [17]

Related Research Articles

<span class="mw-page-title-main">Osteoporosis</span> Skeletal disorder

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone sterility, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly. Bones that commonly break include the vertebrae in the spine, the bones of the forearm, the wrist, and the hip. Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, the person may have chronic pain and a decreased ability to carry out normal activities.

Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

<span class="mw-page-title-main">Bisphosphonate</span> Pharmaceutical drugs for preventing bone loss

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 have two phosphonate groups. They are thus also called diphosphonates.

<span class="mw-page-title-main">Paget's disease of bone</span> Disease affecting bone remodeling

Paget's disease of bone is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, fracture or arthritis of associated joints.

<span class="mw-page-title-main">Teriparatide</span> Pharmaceutical drug for treating osteoporosis

Teriparatide, sold under the brand name Forteo, is a form of parathyroid hormone (PTH) consisting of the first (N-terminus) 34 amino acids, which is the bioactive portion of the hormone. It is an effective anabolic agent used in the treatment of some forms of osteoporosis. Teriparatide is a recombinant human parathyroid hormone analog. It has an identical sequence to the 34 N-terminal amino acids of the 84-amino acid human parathyroid hormone.

<span class="mw-page-title-main">Zoledronic acid</span> Chemical compound

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 to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.

<span class="mw-page-title-main">Osteopenia</span> Medical condition

Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteoporosis. In 2010, 43 million older adults in the US had osteopenia. Unlike osteoporosis, osteopenia does not usually cause symptoms, and losing bone density in itself does not cause pain.

<span class="mw-page-title-main">Bone resorption</span> Medical condition

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.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Ibandronic acid</span> Chemical compound

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. It is typically formulated as its sodium salt ibandronate sodium.

<span class="mw-page-title-main">Osteonecrosis of the jaw</span> Medical condition

Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws. Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature.

<span class="mw-page-title-main">Denosumab</span> Human monoclonal antibody

Denosumab is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

<span class="mw-page-title-main">Strontium ranelate</span> Chemical compound

Strontium ranelate, a strontium(II) salt of ranelic acid, is a medication for osteoporosis marketed as Protelos or Protos by Servier. Studies indicate it can also slow the course of osteoarthritis of the knee. The drug is unusual in that it both increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).

Senile osteoporosis has been recently recognized as a geriatric syndrome with a particular pathophysiology. There are different classification of osteoporosis: primary, in which bone loss is a result of aging and secondary, in which bone loss occurs from various clinical and lifestyle factors. Primary, or involuntary osteoporosis, can further be classified into Type I or Type II. Type I refers to postmenopausal osteoporosis and is caused by the deficiency of estrogen. While senile osteoporosis is categorized as an involuntary, Type II, and primary osteoporosis, which affects both men and women over the age of 70 years. It is accompanied by vitamin D deficiency, body's failure to absorb calcium, and increased parathyroid hormone.

Steroid-induced osteoporosis is osteoporosis arising from the use of glucocorticoids analogous to Cushing's syndrome but involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisone is a main candidate after prolonged intake. Bisphosphonates are beneficial in reducing the risk of vertebral fractures. Some professional guidelines recommend prophylactic calcium and vitamin D supplementation in patients who take the equivalent of more than 30 mg hydrocortisone, especially when this is in excess of three months. The use of thiazide diuretics, and gonadal hormone replacement has also been recommended, with the use of calcitonin, bisphosphonates, sodium fluoride or anabolic steroids also suggested in refractory cases. Alternate day use may not prevent this complication.

<span class="mw-page-title-main">Medication-related osteonecrosis of the jaw</span> Medical condition

Medication-related osteonecrosis of the jaw is progressive death of the jawbone in a person exposed to a medication known to increase the risk of disease, in the absence of a previous radiation treatment. It may lead to surgical complication in the form of impaired wound healing following oral and maxillofacial surgery, periodontal surgery, or endodontic therapy.

<span class="mw-page-title-main">C-terminal telopeptide</span> Chemical compound

The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is the C-terminal telopeptide of fibrillar collagens such as collagen type I and type II. It is used as a biomarker in the serum to measure the rate of bone turnover. It can be useful in assisting clinicians to determine a patient's nonsurgical treatment response as well as evaluate a patient's risk of developing complications during healing following surgical intervention. The test used to detect the CTX marker is called the Serum CrossLaps, and it is more specific to bone resorption than any other test currently available.

<span class="mw-page-title-main">Eldecalcitol</span> Chemical compound

Eldecalcitol is an analog of calcitriol, the active form of vitamin D.

<span class="mw-page-title-main">Osteolytic lesion</span>

An osteolytic lesion is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density, although many other diseases are associated with this symptom. Osteolytic lesions can cause pain, increased risk of bone fracture, and spinal cord compression. These lesions can be treated using biophosphonates or radiation, though new solutions are being tested in clinical trials.

<span class="mw-page-title-main">Discovery and development of bisphosphonates</span> Drugs used to treat bone disorders

Bisphosphonates are an important class of drugs originally commercialised in the mid to late 20th century. They are used for the treatment of osteoporosis and other bone disorders that cause bone fragility and diseases where bone resorption is excessive. Osteoporosis is common in post-menopausal women and patients in corticosteroid treatment where biphosphonates have been proven a valuable treatment and also used successfully against Paget's disease, myeloma, bone metastases and hypercalcemia. Bisphosphonates reduce breakdown of bones by inhibiting osteoclasts, they have a long history of use and today there are a few different types of bisphosphonate drugs on the market around the world.

References

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  16. Tripathi DK (2013-09-30). Essentials of medical pharmacology (Seventh ed.). New Delhi. ISBN   978-9-350-25937-5. OCLC   868299888.{{cite book}}: CS1 maint: location missing publisher (link)
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