Ibandronic acid 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 to treat osteoporosis. Evidence shows that they reduce the risk of fracture in ...

medication used in the prevention and treatment of

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

and metastasis-associated skeletal fractures in people with cancer. It may also be used to treat

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium 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 def ...

(elevated blood

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

levels). It is typically formulated as its

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

ibandronate sodium. It was patented in 1986 by

Boehringer Mannheim F. Hoffmann-La Roche AG, commonly known as Roche (), is a Swiss multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on ...

and approved for medical use in 1996.

Medical uses

Ibandronate is indicated for the treatment and prevention of osteoporosis in post-menopausal women. In May 2003, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved ibandronate as a daily treatment for post-menopausal osteoporosis. The basis for this approval was a three-year, randomized,

double-blind In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

-controlled

trial In law, a trial is a coming together of parties to a dispute, to present information (in the form of evidence) in a tribunal, a formal setting with the authority to adjudicate claims or disputes. One form of tribunal is a court. The tribunal, w ...

women with post-menopausal osteoporosis. Each participant also received daily oral doses of

and 400IUs nternational unitsof

vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

. At the study's conclusion, both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug. Ibandronate is efficacious for the prevention of metastasis-related bone fractures in multiple myeloma, breast cancer, and certain other cancers.

Adverse effects

In 2008, the US

(FDA) issued a communication warning of the possibility of severe and sometimes incapacitating bone, joint or muscle pain. A study conducted by the American Society of Bone and Mineral Research concluded that long-term use of

bisphosphonates 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 to treat osteoporosis. Evidence shows that they reduce the risk of fracture in p ...

, including Boniva, may increase the risk of a rare but serious fracture of the femur.; The drug also has been associated with

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 ...

, a relatively rare but serious condition.

Pharmacology

Mechanism of action

Nitrogen containing bisphosphonates, which include ibandronate,

pamidronate Pamidronic acid or pamidronate disodium or APD (marketed as Aredia among others), is a nitrogen-containing bisphosphonate used to prevent osteoporosis. It was patented in 1971 and approved for medical use in 1987. Medical uses It is used to pr ...

and

alendronate 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 supplementa ...

exert their effects on osteoclasts mainly by inhibiting the synthesis of isoprenoid lipids such as

isopentenyl diphosphate Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the ''non-mevalonate'' MEP pathway of i ...

(IPP),

farnesyl diphosphate Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is the precursor to all sesquiterpenes, which comprises thousands of compounds. These include all sesquiterpenes as well as sterols and carotenoids. It is also used in the syn ...

(FPP), and

geranylgeranyl diphosphate Geranylgeranyl pyrophosphate is an intermediate in the biosynthesis of diterpenes and diterpenoids. It is also the precursor to carotenoids, gibberellins, tocopherols, and chlorophylls. It is also a precursor to geranylgeranylated proteins, whic ...

(GGPP) via the

mevalonate pathway The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl ...

. These isoprenoids are used in posttranslational modifcation(prenylation) of small GTPases such as Ras,

Rho Rho (; uppercase Ρ, lowercase ρ or ; or ) is the seventeenth letter of the Greek alphabet. In the system of Greek numerals it has a value of 100. It is derived from Phoenician alphabet, Phoenician letter resh . Its uppercase form uses the same ...

, and

Rac RAC or Rac may refer to: Organizations * Radio Amateurs of Canada * RATCH-Australia Corporation, electricity generator * Refugee Action Collective (Victoria), Melbourne, Australia * Religious Action Center of Reform Judaism, US * Rent-A-Cent ...

. These prenylated GTPases are necessary for various cellular processes including osteoclast morphology, endosome trafficking, and

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

Society and culture

Brand names

Ibandronic acid is sold under the brand names Boniva, Bondronat, Bonviva, Bandrone, Ibandrix, Adronil, Bondrova, Bonprove, and Fosfonat.

References

{{Authority control Amines Bisphosphonates Farnesyl pyrophosphate synthase inhibitors Drugs developed by Hoffmann-La Roche Drugs developed by Genentech Drugs developed by GSK plc