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Trade names | Skelid |
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ECHA InfoCard | 100.121.105 |
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Formula | C7H9ClO6P2S |
Molar mass | 318.60 g·mol−1 |
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Tiludronic acid (INN; also known as tiludronate) is a bisphosphonate used for treatment of Paget's disease of bone (osteitis deformans) in human being medicine. It has the tradename Skelid. In veterinary medicine, tiludronic acid is used to treat navicular disease and bone spavin in horses. Its tradenames are Tildren and Equidronate. It is approved for treatment of navicular disease and distal, tarsal osteoarthritis in Europe, [1] and was approved for treatment of navicular disease in the United States in 2014.
Tiludronate is a non-nitrogenous bisphosphonate that inhibits osteoclasts, the primary cell responsible for the breakdown of bone required for bone remodeling. Non-nitrogenous bisphosphonates are metabolized by osteoclasts to compounds that then replace a portion of the adenosine triphosphate (ATP) molecule, making it non-functional. These non-functional molecules then competitively inhibit ATP in the cell, reducing cell energy and leading to apoptosis. [2] Decreased levels of osteoclasts subsequently reduce the degree of breakdown of bone and bone turnover. Non-nitrogenous bisphosphonates are less potent than nitrogenous bisphosphonates.
Bisphosphonate | Relative potency |
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Etidronate | 1 |
Tiludronate | 10 |
Pamidronate | 100 |
Aledronate | 100-500 |
Ibandronate | 500-1000 |
Risedronate | 1000 |
Zoledronate | 5000 |
Tiludronate has been used primarily for the treatment of diseases in horses that are associated with inappropriate osteolysis, such as navicular disease [4] and osteoarthritis. It has specifically been shown to improve lameness in horses with osteoarthritis of the distal hock joints (bone spavin) [5] and vertebral column. [6]
Tildren is administered intravenously. It is labeled for 0.1 mg/kg dosing, once daily for 10 days by slow intravenous injection, which for a 500 kg horse works out to be 1 vial per day. However, one study giving all 10 doses at once (1 mg/kg IV as a single CRI) was found to have the same pharmacological effects, and is used clinically. [7] It may be given systemically or locally, by regional limb perfusion. Although RLP is thought to have certain benefits, including decreased cost and reduced risk of adverse effects, some diseases must be treated systemically, such as osteoarthritis of the vertebral column. Systemic administration is often given by adding a 1 mg/kg dose into a 1-liter fluid bag, which is slowly given over 60–90 minutes. Its effects are reported to last 4 months or longer, with a peak effect 6–8 weeks post treatment. [8] The effects of regional limb perfusion has come into question due to in vitro studies showing that high doses given by RLP or intraarticular injection may damage articular cartilage by chondrocyte apoptosis. [9] Further studies are needed to evaluate the safety of Tildren administration via RLP.
Tildren has been shown to have several adverse effects. [10]
It is not recommended for animals under four years of age, due to lack of studies evaluating its safety in growing animals, nor for pregnant or lactating animals, since its effect on the fetus has not been studied.
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.
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.
Phenylbutazone, often referred to as "bute", is a nonsteroidal anti-inflammatory drug (NSAID) for the short-term treatment of pain and fever in animals.
Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most abundant monosaccharides. Produced commercially by the hydrolysis of shellfish exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat, glucosamine has many names depending on country.
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.
Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop which may limit the ability to move. Complications may include collapse of the bone or nearby joint surface.
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.
Navicular syndrome, often called navicular disease, is a syndrome of lameness problems in horses. It most commonly describes an inflammation or degeneration of the navicular bone and its surrounding tissues, usually on the front feet. It can lead to significant and even disabling lameness.
Bone spavin is a bony growth within the lower hock joint of horse or cattle. It is caused by osteoarthritis, and the degree of lameness that results can be serious enough to end a horse's competitive career.
Flunixin is a nonsteroidal anti-inflammatory drug (NSAID), analgesic, and antipyretic used in horses, cattle and pigs. It is often formulated as the meglumine salt. In the United States, it is regulated by the U.S. Food and Drug Administration (FDA), and may only be lawfully distributed by order of a licensed veterinarian. There are many trade names for the product.
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).
Tepoxalin, marketed under the brand name Zubrin among many others, is a non-steroidal anti-flammatory drug (NSAIDs) generally used in veterinary medicine to reduce swelling in animals with osteoarthritis. In rare circumstances, Tepoxalin can also be used in human pharmacology to relieve pain caused by musculoskeletal conditions such as arthritis and hip dysplasia.
Clodronic acid (INN) or clodronate disodium (USAN) is a first generation (non-nitrogenous) bisphosphonate. It is an anti-osteoporotic drug approved for the prevention and treatment of osteoporosis in post-menopausal women and men to reduce vertebral fractures, hyperparathyroidism, hypercalcemia in malignancy, multiple myeloma and fracture related pain because of its potent anti-inflammatory and analgesic effects shown as a reduction in inflammatory markers like IL-1β, IL-6, and TNF-α.
Meclofenamic acid is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs) and was approved by the US FDA in 1980. Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins.
Lameness is an abnormal gait or stance of an animal that is the result of dysfunction of the locomotor system. In the horse, it is most commonly caused by pain, but can be due to neurologic or mechanical dysfunction. Lameness is a common veterinary problem in racehorses, sport horses, and pleasure horses. It is one of the most costly health problems for the equine industry, both monetarily for the cost of diagnosis and treatment, and for the cost of time off resulting in loss-of-use.
Limb perfusion is a medical technique that is used to deliver drugs locally directly to a site of interest. It is commonly used in human medicine for administration of anticancer drugs directly to an arm or leg. It is also used in veterinary medicine to deliver drugs to a site of infection or injury, as well as for the treatment of cancer in dogs. In both cases, a tourniquet is used to reduce blood flow out of the area that is being treated.
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.
The treatment of equine lameness is a complex subject. Lameness in horses has a variety of causes, and treatment must be tailored to the type and degree of injury, as well as the financial capabilities of the owner. Treatment may be applied locally, systemically, or intralesionally, and the strategy for treatment may change as healing progresses. The end goal is to reduce the pain and inflammation associated with injury, to encourage the injured tissue to heal with normal structure and function, and to ultimately return the horse to the highest level of performance possible following recovery.
Bisphosphonates are an important class of drugs originally introduced about half a century ago. 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.
Alicia L. Bertone is an American academic, administrator, researcher, and veterinary surgeon. She is a professor and a provost in the Office of Academic Affairs at the Ohio State University. Bertone has worked as the Vice-Provost of Graduate Studies, Associate Vice Provost of Data and Analysis, the ENGIE-Axium Endowed Dean of the Graduate School, and the Trueman Family Endowed Chair at the Ohio State University. Bertone is a Professor of Veterinary Clinical Sciences, and, as the Trueman Endowed Chair, established and directed the Comparative Orthopedic Research Laboratory at the University.