Your Equine Needs Under ONE Roof!

Your Equine Needs Under ONE Roof!

Thursday, October 11, 2007

TILDREN INJECTION

TRIDEN INJECTION




TREATMENT FOR LAMENESS ASSOCIATED WITH BONE AND CARTILAGE CHANGES IN HORSES





COMPOSITION
TILUDRONIC ACID 50mg/vial.


ACTIONS
Tiludronic acid belongs to the bisphosphonate therapeutic class, a class of product with activity on bone metabolism. The main pharmacological property of TILDREN Injection is to reduce bone resorption by inhibiting the activity of osteoclast.

TILDREN Injection acts as a regulator of bone remodelling in all situations involving excessive bone resorption. This regulator effect is not associated with a negative effect of bone formation or bone mineralisation at the recommended therapeutic dosage.

Areas of reduced bone density are a pathological change common to most cases of Navicular Disease and Bone spavin and are due to inappropriate resoption of bone (osteolysis). In double-blind, placebo-controlled clinical trials for both conditions, TILDREN treatment induced a clear improvement as demonstrated by long-term reduction in lameness and progressive resumption of sporting activity.


In another double-blind, placebo-controlled clinical trial into the treatment of back pain associated with bony lesions of the vertebral column, TILDREN treatment induced a clear improvement in back flexibility, however further research is required to add this indication as a registered claim. Other studies have shown that TILDREN treatment can prevent the bone loss, which usually occurs during inactivity in horses, as shown by measurements of bone density in spelling horses.

TILDREN Injection has also demostrated anti-arthritic properties in a model of poly-arthristis in rats. In vitro date identified inhibiting effects on the secretion of enzymes which degrade cartilage matrix.


INDICATIONS
HORSES: Treatment of lameness associated with bone and cartilage changes such as those observed in Navicular Disease and Bone Spavin.


DOSAGE AND ADMINISTRATION
DOSAGE: 0.1mg Tiludronic acid per kg bodyweight once daily for 10 days by slow intravenous injection. i.e. 10mL (1 vial) of reconstituted solution per 500kg bodyweight per day for 10 days.


PRESENTATION
CARTON CONTAINS: 10 vials of 50mg freeze-dried powder (Tildren) and 10 vails of 10mL solvent (Water for injection). Each carton provides a 10-day treatment course for a 500kg horse.


STORAGE
Store below 25 celcius (air conditioning) in outer carter.






EFFECT OF TILUDRONATE ON BONE RESOPTION






(1) Binding of Tiludronate via a covalent bond to the mineral phrase of the bone (the hydroxyapatite). This binding occurs preferentially at the remodelling sites.

(2) Acidification of th emedium resultingh from the initiation of the resoption process - this breaks the Tilundronate-hydroxyapatite bond. In this way Tildronate is released into the resorption cavity.

(3) Penetration of Tiludronate into the osteoclast.

(4) . Inhibition of the proton pump...

. Disruption of the cytoskeleton leading to the loss of the ruffled border.
. Formation of a cytotoxic ATP analogue, which causes the death of the osteoclast.


AMINO ACID-AMP + PYROPHOSPHATE ~~~ ATP + AMINO ACIDS.


Tiludronate replaces the pyrophosphate, hence;



AMINO ACID-AMP + TILUDRONATE ~~~ ATP ANALOGUE + AMINO ACID.


ACTION OF THE OSTEOBLAST
Osteoblast particularly produce interleukin-6 which activates the osteoclasts and thus initates resorption. Tiludronate inhibits the osteoblastic synthesis of interleukin-6.









EFFECT OF TILUDRONATE ON CALCIUM


. Work carried out by Barbier shows that th eintestinal absorption of calcium is increased in a 'DOSE DEPENDENT' manner by Tiludronate, without increasing the excretion of calcium via the urine.




. Moreover, Tildronate facilitates the binding of blood calcium to bone, by increasing the size of existing hydroxyapatite crystals or of crystals being formed.
. Tiludronate limits the release of bone calcium by inhibiting resorption.


THESE RESULTS SHOW THAT TILUDRONATE ENHANCES CALCIUM ABSORPTION AND INCREASES BONE DENSITY.

CONCLUSION
TILUDRONATE IS A REGULATOR OF BONE REMODELLING:
. it reduces bone resorption
. it does not have a negative effect on bone formation
. it has positive effects on mineralisation and increases bone density.

As a consequence of its various pharmacological properties, Tiludronate is very beneficial in the treatment of lameness where bone pathology is involved, in particular, where radiographs show that osteolysis and sclerosis are features of the pathology.


EFFECT ON CARTILAGE
In vitro studies have shown that Tiludronate inhibits the secretion, mediated by interleukin-1, of enzymes that degrade the cartilaginous matrix.

These enzymes (collagenase and proteoglycan-degrading enzyme) are produced by chondrocytes and the synovial cells.

This property of Tiludronate may be beneficial in treating degenerative osteo-articular pathologies.



STUDY OF THE BONE DISTRIBUTION IN HORSES OF TILUDRONATE AS A FUNCTION OF TIME.

PROTOCOL
. 8 horses (4 males, 4 females).
. 0.1 mg/kg/day (as C tiludronate) for 10 consecutive days via the IV route.
. Study duration: 6 months.

MEASUREMENT OF THE TILUDRONATE CONCENTRATION: DO + 10 DAYS, DO + 3 MONTHS, DO + 6 MONTHS IN THE FEMUR, THE THIRD TARSAL BONE, THE THIRD METACARPAL BONE AND THE NAVICULAR BONE.


RESULTS
. The same distribution pattern was observed for males and females, however, the dose bound in the bone was lower for the females.

. The bone concentration varied as a function of the bone studied.

. The concentration in the bone diminished very slowly between 0 and 3 months; the reduction was more marked after 6 months.



PERCENTAGE OF HORSES WITHDRAWN FROM THE TRIAL AFTER 1 OR 2 MONTHS DUE TO AN INSUFFICIENT RESPONSE TO THE TREATMENT.



A FAILURE RATE
The investigators could withdraw a horse from the study, if the response to treatment was considered to be insufficient at the 1-month or 2-month examination.

- 55% OF THE HORSES IN THE PLACEBO GROUP WERE WITHDRAWN FROM THE STUDY.

- NO HORSE IN THE TILDREN GROUP WAS WITH DRAWN FROM THE STUDY.







EVALUATION OF THE DEGREE OF LAMENESS

In the placebo group: in the first 2 months there was a reduction in the number of horses presenting with moderate to extreme lameness. After 2 months there was a relapse and at 6 months, 90% of the horses in this group were lame.


IN THE TILDREN GROUP:
. There was a progressive and long lasting improvement. After 6 months, 60% of the horses were no longer lame or showed only mild signs, demonstrating the mid-to long-term effect of Tildren.







LEVEL OF ACTIVITY
The horse's level of activity is an essential criteria in evaluating the benefit of a treatment. For the treatment to be truly satisfactory, it is important that the horse can resume its sporting activity.

The level of activity is evaluated as a function of the type of activity normally carried out by the horse on a scale of 0 (very little activity).

ACTIVITY WAS CONSIDERED TO HAVE BEEN RESUMED IF THE SCORE WAS 6 OR 7.
. In the Tildren group, a progressive and gradual recovery was noted in the horses's activity.

. In the placebo group, the number of horses recovering normal activity levels fluctuated from one consultation to another. At 6 months, none of the horses had a normal level of activity.

. After 6 months: more that 67% of the horses had recovered a normal level of activity.

. There was a significant difference between the Tildren group and the placebo group: p=0.01



PERCENTAGE OF HORSES WITHDRAWN FROM THE TRIAL AFTER 1 OR 2 MONTHS DUE TO AN INSUFFICIENT RESPONSE TO THE TREATMENT.


A FAILURE RATE
The investigators could withdraw a horse from the study, if the response to treatment was considered to be insufficient at the 1-month or 2-month examinations.

The failure rate corresponds to the percentage of horses withdrawn from the study because of a response deemed to be insufficient. The rate was measured in each group.

As can be seen in the graph, by the 2-month examination the two groups were very significantly different:
- 38 of the horses in the placebo group were withdrawn from the study.
- No horses in the TILDREN group were withdrawn from the study.




. After 1 month, almost 60% of the treated horses were either no longer lame or were slightly lame.

. After 2 months, there was a clear increase in the number of horses who were either no longer lame or only slightly lame: 70% of the horses.

. This improvement was long-lasting. After 6 months, almost 60% of the horses were no longer lame or showed only mild signs, demonstrating the mid-to long-term effect of Tildren.

135 comments:

Anonymous said...

I am considering Tildren for my rather young and sound horse due to radiographs reviewed by 2 very qualified vets - I have heard of some "side" effects - can anyone comment?

Anonymous said...

I Treated my horse 4 years ago with Tildren, at the time it was only a trial and error treatment as it had only just began to be used in studies around the world.
My vet had diagnosed my horse with early stage navicular disease. He was severely lame and un ridable.
Four years on and he is 100% sound and showing no signs of re occuring lameness yet.....
He competes at State level Dressage and is Training Medium Dressage at the moment.
He was 6 Years old when he was treated and he is almost 10 Yrs old now. I am unsure how long the effects of the tildren will last, if anyone knows let me know. As i would happily treat my horse again.
He has had NO side effects from this drug.
Hope that helps....

Anonymous said...

Symptoms of colic are very common, especially if it is administered 10 vials in a liter of saline over 2-3 hours, which many vets are now doing. To decrease the risk, you can do as I have, 2 vials once a day for 5 days, as slow as you can possibly give an IV injection. Other than mild colic, I have never seen a side effect of this wonderful drug.

Anonymous said...

My horse was conically lame with nevicular and over the summer we took him down to Dr. Kent Allen's at VEI in VA. After ultrasound and an MRI scan we opted for the Tildren injected systemically along with treatment of both bursas because of mild bersitus in both front hooves. He's done amazing with the drug!

Anonymous said...

Does anyone have any experience injecting Tildren directly into a joint rather than using it intravenously? I've been told that injecting Tildren directly into the joint is the newest way to use this product, and I'd like to hear from anyone that has used it in this way, and what kind of results they had. I'm considering this treatment for a stifle ocd. Thanks.

Anonymous said...

My 12yr old QH had a Tildren joint injection this afternoon. We went through IRAP, with soundness lasting appro. 3 weeks. In his case, there appears to be both bone changes and inflammation within the coffin joint. With the nearest MRI at least a 9 hour drive away, we really don't know for sure but are treating for both. I am very interested in hearing from anyone who has results from IRAP and/or Tildren (joint not IV). Thanks

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Mary said...

my horse is having IRAP in coffin joint at the moment aswell as just having the Tildren intravenously yesterday to see if helps for the fracture to her face as the bone is active. Fracture so severe cannot have plate put into the face. I am hoping for a good results from Tildren. will post result in a few months.

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I used Tildren on my 13 year old Holsteiner who jumps 1.40 meters due to neck and si joint arthritis. We did a bone scan and he had no other inflammation or bone issues. He is now using himself in ways he never did before and developing an amazing muscle in his neck and hind-end. Apparently Tildren works for more than just navicular!

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