Hardy BT, de Brito Galvao JF, et al. Treatment of ionized hypercalcemia in 12 cats (2006-2008) using PO-administered alendronate. J Vet Intern Med. 2015;29(1):200-6.
There are variety of etiologies for hypercalcemia in small animal patients: neoplasia, chronic kidney disease (CKD), toxicity (often with Vitamin D-containing products), primary hyperparathyroidism, hypoadrenocorticism, granulomatous diseases, and osteolytic diseases, with malignancy-associated hypercalcemia and CKD considered the most common. In the last two decades, a syndrome of idiopathic hypercalcemia (IHC) has been identified in cats. In IHC, which is parathyroid-independent, both total serum calcium and circulating ionized calcium (iCa) concentrations are elevated, and this suppresses parathyroid hormone (PTH) production, so that serum PTH levels are are low-normal to low. In addition, serum magnesium and 25(OH)-vitamin D levels are normal in cats with IHC, and blood levels of PTH-related polypeptide (PTHrP, produced by some malignant tumors), are not detectable.
Currently IHC is considered the most common cause of hypercalcemia in felines, followed by hypercalcemia of malignancy. If hypercalcemia is associated with CKD, it is usually reflected only in elevated serum total calcium; ionized calcium is rarely increased in CKD. Any cat may be affected with IHC; no age, breed, or sex predilection has been identified, but IHC may be more common in longhaired cats. Although many cats with IHC have no clinical signs, some will experience weight loss, anorexia, gastrointestinal signs, dysuria, inappropriate urination, or urolithiasis (usually oxalates), and may develop azotemia later in the course of the disease. Most cats with IHC are middle-aged (5-9 years), with mild to moderate increases in total and ionized serum calcium concentrations.
Calcium homeostasis is maintained by a complicated balance of dietary calcium absorption from the gastrointestinal tract, calcium reabsorption and excretion in the kidney, and production and reabsorption of bone. Cats with IHC are often initially asymptomatic and the condition is generally slowly progressive. First line treatments often include a nonacidifying, high fiber diet and prednisolone. These treatments, however, are not always successful, and response to them may be transient. Increased resorption of calcium from bone may be an important cause or contributing mechanism of IHC in cats, and may explain why dietary and prednisolone therapy do not always stop progression of the syndrome.
Bisphosphonates are another potential therapy for IHC, as these drugs reduce bone resorption by inhibiting osteoclast function and may directly induce osteoclast apoptosis. Hitherto, use of bisphosphonates in veterinary medicine was limited to intravenous use in dogs with osteolytic neoplasia and in 2 cats with ionized hypocalcemia. In this prospective study of 12 cats with ionized hypercalcemia of idiopathic origin, patients were treated with the nitrogen-containing bisphosphonate alendronate at dose of 5-20 mg per cat per os (PO) every 7 days. Serum iCa was measured in all patients prior to beginning treatment with alendronate, and again after 1, 3, and 6 months of treatment, and the alendronate dosage was adjusted based on the serum iCa levels. Serum PTH, PTHrP, 25-hydroxycholecalciferol, and serum iCa concentrations were evaluated in all cats; the first three analytes were low or within the normal reference range in all subjects. Eight of the cats had an abdominal ultrasound examination, 4 had abdominal radiography, and all 12 cats had thoracic radiography; findings in these imaging studies did not identify any potential cause for the hypercalcemia.
During the 6-month treatment course of the study, in which all patients started on 5-10 mg of alendronate PO q 7 days (most cats were started on 10 mg PO weekly), 8 of the 12 cats required dose escalation. Two required dose reduction due to the development of hypocalcemia, and one cat maintained normal serum iCa concentrations on 5 mg PO weekly throughout the entire study period. The alendronate treatments resulted in a decrease in serum iCa in all 12 cats by a median of -0.34 mmol/L after 6 months of treatment. Eight of the cats had serum iCa decrease to within the reference range (1.15-1.4 mmol/L) at some point during treatment, which would suggest that osteoclastic activity increasing bone resorption is an important contribution to IHC in some cats. In 3 of the cats, serum iCa did not decrease by more than 20% or there were only transient decreases in serum iCa, even with dose escalation. The experience with these latter patients suggests that IHC may represent more than one disease process. In all animals the alendronate therapy was well tolerated, with no adverse effects reported in any of the cats.
Alendronate is now recommended to be given on an empty stomach, and as many cats will only take tablets in or with food or treats, dosing can be problematical for some owners. In addition, it is now also recommended that the cat's fast continue for 2-4 hours after alendronate administration. During the course of this study, the owners were not advised to fast their cats before and after administration of alendronate, because the researchers were not aware that gastric contents other than water could impair gastrointestinal absorption of this medication. The drug can be very irritating to the oral cavity and esophagus, and development of esophageal strictures subsequent to esophageal erosion or ulceration has been reported in humans taking alendronate. Because of this, owners were instructed to follow administration of alendronate tablets with 6 mL of tap water PO. The flavoring in the available liquid suspension of alendronate was considered to be unpalatable to cats, so the the liquid was not prescribed for any of the study cats. Future studies of alendronate in treatment of IHC in cats should focus on administration of the drug to a larger study group over a longer period, preferably involving a control placebo treatment population. [PJS]
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Whitney JL, Barrs VR, et al. Use of bisphosphonates to treat severe idiopathic hypercalcemia in a young Ragdoll cat. J Feline Med Surg. 2011;13:129-34.