Alendronate Dosing Protocol for Cats with Idiopathic Hypercalcemia

I have a quick question for you about the use of alendronate for treatment of cats with idiopathic hypercalcemia. First of all, I wanted to find out if you recommend this treatment, and what your experience is with the drug.

The protocol that I've been using is to start with an oral dose of 10 mg once weekly, and then increase the dose to 20 mg once weekly if needed. In a few cats, I've had to go as high as 30 mg per week to lower the total and ionized calcium concentrations.

Have you ever done twice weekly dosing? I was recently referred a hypercalcemic cat whose dose was changed from 20 mg once a week to 10 mg twice a week by the veterinarian in the hopes that twice weekly dosing would be more effective. I know it theoretically can be given twice weekly, but was wondering if you've found that twice weekly dosing was more effective.

Thank you for your help.

My Response:

As you know, treatment for idiopathic hypercalcemia in cat is currently empiric, since the cause of the disorder remains unknown. I generally start with a change in diet as a first step in treatment (1), since normocalcemia is sometimes restored after a change to a different diet. However, even in cats that show an initial response to dietary intervention, the duration of normocalcemia may be short-lived and the hypercalcemia can relapse. In these cats, I then turn to medical therapy (i.e., glucocorticoids or bisphosphonates) to help control the hypercalcemia.

Even though not extensively reported, I consider bisphosphonate therapy with alendronate (i.e, Fosamax, Merck; generic formulations also available) to be a better alternative than prednisolone for most cats with idiopathic hypercalcemia that fail dietary intervention (2-4). The complications I commonly see with chronic high-dose glucocorticoid treatment include muscle wasting and iatrogenic diabetes. Remember that steroids are catabolic for muscle tissue (5,6) and will produce insulin-resistance that can lead to hyperglycemia and overt diabetes mellitus (7).

Alendronate dosing protocol
Most cats with idiopathic hypercalcemia will respond to oral alendronate, at a dose range of 10-40 mg once weekly. Like you, I start with an initial oral dose of 10 mg per week, and then gradually increase the dose based on ionized calcium concentrations monitored at 4-6 week intervals (4).

This treatment protocol will restore normocalcemia in over two-thirds of the hypercalcemic cats treated with an average weekly dose of 15 mg (4). As with dietary therapy, many will eventually show relapse and will require an increase in alendronate dosage or the addition of glucocorticoid therapy. In a few cats, the serum ionized calcium will drop too far, and the dose can be decreased to 5 mg per week or 10 mg given every other week (2,4).

Alendronate is poorly absorbed from the GI tract
The oral bioavailability of alendronate in cats is poor. In one study, the percentage of the drug that was actually absorbed when administered to cats was found be only 3% (8). This percentage fell about 10-fold when alendronate was formulated in tuna juice.

To maximize intestinal absorption of this drug, we recommend that the cats be fasted overnight (12-18 hour fast) prior to the administration of the alendronate. The medication should then be given with 6-ml of plain water (to ensure passage of the tablet into the stomach), and the fast continued for at least 2-4 additional hours (4).  We do not recommend any kind of alendronate that has been formulated by compounding pharmacies in flavored solution or suspension because that will likely lead to a marked decrease in the intestinal absorption.

Twice weekly dosing of alendronate?
I don't see any problem with twice-weekly dosing of the alendronate. However, based on the pharmacokinetics of the drug, it's unlikely to be any more effective than once-weekly dosing. In humans, the original treatment protocols recommended a dosage of 10 mg once a day, but this was subsequently changed to 70 mg per week based on pharmacokinetic studies (9).

Remember, however, that the biggest issue with the use of this drug in cats is the need for prolonged fasting in order to even achieve 3% absorption. If the owners are giving the drug with food, less than 0.5% of the drug will be absorbed, if it's going to be absorbed at all.

Because of the issues associated with the prolonged fasting, I would not recommend twice-weekly dosing in my feline patients. We know that once-weekly dosing works in most cats, and the "stress" associated with twice-weekly prolonged fasting (as well tablet administration followed by a 6-ml flush of water) is just too much for the cat or the owner.

References:

1. Peterson ME. Nutritional management of endocrine disease in cats. Proceedings of the Royal Canin Feline Medicine Symposium 2013;23-28.
2. Hostutler RA, Chew DJ, Jaeger JQ, et al. Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcemia. J Vet Intern Med. 2005;19:29-33.
3. Whitney JL, Barrs VR, Wilkinson MR, et al. Use of bisphosphonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat. J Feline Med Surg. 2011;13:129-134.
4. de Brito Galvao JF, Chew DJ, Parker VJ. Management of idiopathic hypercalcemia. In: Little SE, ed. August's Consultations in Feline Internal Medicine: Elsevier, in press.
5. Horber FF, Scheidegger JR, Grunig BE, et al. Thigh muscle mass and function in patients treated with glucocorticoids. Eur J Clin Invest 1985;15:302-307. 
6. Menconi M, Fareed M, O'Neal P, et al. Role of glucocorticoids in the molecular regulation of muscle wasting. Crit Care Med 2007;35:S602-608. 
7. Lowe AD, Graves TK, Campbell KL, et al. A pilot study comparing the diabetogenic effects of dexamethasone and prednisolone in cats. J Am Anim Hosp Assoc 2009;45:215-224. 
8. Mohn KL, Jacks TM, Schleim KD, et al. Alendronate binds to tooth root surfaces and inhibits progression of feline tooth resorption: a pilot proof-of-concept study. J Vet Dent. 2009;26:74-81.
9. Fosamax (Alendronate sodium). Product insert. www.merck.com.