JVD 2009 2 Alendronate Binds to Tooth Root Surfaces and Inhibits Progression of Feline Tooth Resorption Flashcards
According to this study what percentge of older cats are affected by tooth resorption?
67%
What activity of bisphosphonates might render them useful in decreasing tooth resorotion in cats.
Bisphosphonates bind to exposed hydroxyapatite and act on osteoclasts in bone to inhibit their recruitment and resorptive activity, and to induce apoptosis.
Whay was alendronate selected to use in this study?
Alendronate was selected to test this hypothesis because of its potency and established efficacy against osteoporotic disease in humans and because
the odontoclasts responsible for the loss of tooth substance in TR are ontologically,
histologically and biochemically indistinguishable from osteoclasts.
What three things were examined in order to assess the hypothesis in this study?
Alendronate distribution
Alendronate bioavailability
Inhibition of tooth resorption
How was alendronate distribution determined?
3 cats injected with 0.05mg/kg of 12mg/ml alendronate solution IV and then blood samples taken at 5,30, 120, 360& 1440 mins post injection. They were then euathanased and mandibles and femurs assessed for the amount of radioactivity as were the ehads after removal of the teeth and mandibles.
How was alendronate oral bioavailability detremined?
Urine was collected form 12 cats distributed in]to 4 groups . group 1 :3.0mg/kg alendronate in water, group 2: 9.0 mg/kg alendronate in water, group 3: 9.0mg/kg in tuna water and group 4: no alendronate. urine was collected for 24hrs post dosing using non absorbent litter.
The 24-hour urinary clearance of a known dose of [butyl-4-14C-
]-alendronate was determined in the tissue distribution experiment.
The calculated clearance rate was then used to back calculate the
oral bioavailability that would have resulted in the observed total
urinary output of alendronate.
How was inhibition of tooth resorption assessed?
10 female cats in an 11 month study. One was culled from study 4 given vehicle and 5 given alendronate once a week at 3.0mg/kg from week 0-22 and then 9.0mg/kg twice weekly in tuna water from week 23- end study.
they were radiogrpahed at the start of the study and at months 4, 7 and 11. These were read by two separate dentists( human & veterinary) and evaluated as decreased, unchanghed or increased with respect to the resorptive lesions already defined
When was the peak plasma alendronate level achieved and how quickly did alendronate reach beaseline levels?
peak levels were seen 5 minutes after administration and baseline levels were reached by 6 hours.
What tissues had the highest levels of alendronate?
The alendronate concentration in mineralized tissues was considerably higher especially in samples rich with trabecular bone such as the proximal and distal thirds of the femur. In the teeth, the alendronate concentrations were quite high, approaching
the levels seen in trabecular bone
How much alendronate is excreted in the urine in the first 24hrs?
The dose is rapidly cleared from serum, with approximately 50 % being excreted in the urine within the first 24-hours post dosing.
Why was the dose rate of alendronate increased when given with tuna water?
The oral bioavailability of the tuna water formulation is only approximately 0.4 %,
consistent with known interactions of alendronate with food. Despite a 6 fold increase in dose rate the effective dose was slightly lower than the 3.0mg/kg in food.
During what period of dosing was there a statistically different rate of progression of tooth resorption in the treated cat group?
4-11months
What did the study demonstrate and therefore suggest should be done into the future?
The current study demonstrates that alendronate treatment slows or arrests the progression of TR in cats and may have the potential to permit affected teeth to be salvaged.
Although additional clinical trials are needed to confirm these observations, determine the optimally effective dose, and confirm safety of the optimally effective dose.
