Tiludronic acid (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

; also known as tiludronate) 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 ...

used for treatment of

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 ...

(osteitis deformans) in human medicine. It has the tradename Skelid. In veterinary medicine, tiludronic acid is used to treat

navicular disease 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 t ...

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, and was approved for treatment of navicular disease in the United States in 2014.

Mechanism of action

Tiludronate is a non-nitrogenous bisphosphonate that 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 ...

s, the primary cell responsible for the breakdown of bone required for

bone remodeling Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called ''bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). ...

. Non-nitrogenous bisphosphonates are metabolized by osteoclasts to compounds that then replace a portion of the

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms o ...

(ATP) molecule, making it non-functional. These non-functional molecules then competitively inhibit ATP in the cell, reducing cell energy and leading to

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. Decreased levels of osteoclasts subsequently reduce the degree of breakdown of bone and bone turnover. Non-nitrogenous bisphosphonates are less potent than nitrogenous bisphosphonates.

Use in equine medicine

Tiludronate has been used primarily for the treatment of diseases in horses that are associated with inappropriate osteolysis, such as

and osteoarthritis. It has specifically been shown to improve lameness in horses with osteoarthritis of the distal hock joints ( bone spavin) and vertebral column.

Method of administration

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. 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. 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. Further studies are needed to evaluate the safety of Tildren administration via RLP.

Adverse reactions and contraindications

Tildren has been shown to have several adverse effects. * Signs of

colic Colic or cholic () is a form of pain that starts and stops abruptly. It occurs due to muscular contractions of a hollow tube (small and large intestine, gall bladder, ureter, etc.) in an attempt to relieve an obstruction by forcing content out. ...

, which is usually self-limiting, occurs in 30-45% of horses. *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

* Electrolyte disturbances: primarily calcium, magnesium, and potassium, which can last for several hours. Caution should be used in horses with disease processes that could be affected by electrolyte disturbances, such as

hyperkalemic periodic paralysis Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability ...

or cardiac disease. *

Kidney damage Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...

: it is eliminated by the kidney and is not recommended for use in animals with impaired renal function. * Less serious reactions include stiffness of the neck, decreased appetite, fever, and increased urination. 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.

References

External links

Prescribing information for Skelid

tildren.com
{{Bisphosphonates Bisphosphonates Equine medications