Page 170 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

160 ELECTROLYTE DISORDERS

has not yet been established because lymphocytolysis can packages of cholecalciferol-containing (vitamin D) rat
make a definitive histopathologic diagnosis of lymphoma poison, and treatment with calcitonin has been reported
much more difficult or impossible. A challenge test for in dogs with hypercalcemia resulting from cholecalciferol
the diagnosis of occult lymphoma has been proposed toxicity. The dosage of calcitonin used in these dogs was
2
using L-asparaginase at 20,000 IU/m intravenously in 8 IU/kg subcutaneously every 24 hours, 194 5 IU/kg
an effort to disturb tumor cell metabolism but not cause subcutaneously every 6 hours, 206 and 4 to 7 IU/kg sub-
cytolysis. Calcium concentrations are measured at base- cutaneously every 6 to 8 hours. 149 Short-term calcitonin
line and then every 12 to 24 hours for 72 hours. A com- treatment (6 U/kg subcutaneously every 8 hours for
plete return of serum calcium concentration to normal 2 days) was not effective in controlling hypercalcemia
suggests occult lymphoma. 178 Once a diagnosis of lym- in dogs when measured 4 days after ingestion of cholecal-
phoma has been made, prednisone is usually administered ciferol. 500 Vomiting was common within 2 hours of cal-
at 1 to 2 mg/kg twice daily concomitant with citonin administration. Calcitonin (4 U/kg every 4 hours
chemotherapy. for the first day and then 8 mg/kg twice daily for the next
Decreased bone resorption after administration of 3 days) decreased serum tCa from nearly 18 mg/dL to 13
glucocorticoids may be the result of impaired osteoclast to 15 mg/dL, but the effect only lasted 4 to 8 hours. 248
maturation and decreased numbers of calcitriol receptors Calcitonin has also been used as part of combination
in bone. 545 Cortisol antagonizes the effects of vitamin D therapy for treatment of hypercalcemia in a cat with
on the intestine in rats. 235 In dogs, chronic oral adminis- granulomatous disease. 368
tration of prednisone (1.2 to 1.5 mg/kg/day) resulted in
decreased serum calcitriol concentrations but caused no Bisphosphonates
change in the number of calcitriol receptors or calcium- Bisphosphonates (formerly misnamed diphosphonates)
binding proteins in enterocytes. 307 Granulomatous are drugs (pyrophosphate analogues) that have been
diseases associated with increased calcitriol synthesis developed to inhibit bone resorption. 58,474 The hypocal-
and hypercalcemia are often sensitive to the effects of cemic effects of bisphosphonates during malignancy
glucocorticoids in reducing the serum calcium concen- are bone related because there is no effect on tumor
tration. 467,528 However, caution is advised because the mass. Bisphosphonates decrease osteoclast activity and
underlying disease (e.g., systemic mycosis) may be wors- function, despite increased numbers of osteoclastspresent
ened. Hypercalcemia associated with hypervitaminosis A as a result of local or humoral mechanisms of osteolysis.
can also be steroid responsive. 41 Their presence in bone interferes with hydroxyapatite
dissolution and exerts direct effects that reduce osteoclas-
Calcitonin tic function. Induction of osteoclast apoptosis appears
Calcitonin treatment may be useful in animals with severe to be the main effect of bisphosphonates. 58 Inhibition
hypercalcemia. Calcitonin should be considered instead of resorption requires 1 to 2 days. Long-term
of prednisone for the treatment of animals without a bisphosphonate administration can lead to decreased
definitive diagnosis. Calcitonin rapidly decreases the osteoclast numbers through lethal injury of osteoclasts
magnitude of hypercalcemia primarily by reducing the and decreased recruitment of new osteoclasts. The
activity and formation of osteoclasts. A maximal decre- magnitude of effect in lowering circulating calcium
ment in serum tCa concentration of approximately concentrations is related to the initial level of hypercalce-
3 mg/dL can be expected. 115 The only known adverse mia, the dose, route administered, and the specific
effects of calcitonin are anorexia and vomiting, but rela- bisphosphonate administered. The duration of initial
tively few treated dogs and cats have been evaluated. Cal- beneficial effect following IV administration of
citonin treatment is expensive; the magnitude of its effect bisphosphonates may last 1 to 4 weeks.
is unpredictable; its effects may be short-lived (hours); Etidronate was the first bisphosphonate to be used
and resistance often develops in a few days. Receptor clinically, and the activity of newer bisphosphonates is
down-regulation is believed to be responsible for devel- often compared with that of etidronate. Bisphosphonates
opment of resistance, a phenomenon that may be delayed that contain a nitrogen side chain have enhanced
by concurrent glucocorticoid treatment. The effective- antiresorptive activity and are called aminobisphos-
ness of calcitonin may be restored after discontinuing phonates (pamidronate, zolendronate, ibandronate).
treatment for 24 to 48 hours. 354 Despite these Early generation bisphosphonates, such as etidronate
limitations, calcitonin in combination with pamidronate and clodronate, are lacking in nitrogen side chains
is considered the best therapy for severe malignancy- and so are less active. The greatest potency to date has
associated hypercalcemia in humans. 123,525 been obtained in those compounds containing a tertiary
The dosage of calcitonin in animals has been amine (zoledronate). 384 Clodronate, pamidronate,
extrapolated from that used in humans (4 IU/kg intrave- alendronate, and residronate have potencies 10, 100,
nously, followed by 4 to 8 IU/kg subcutaneously once or 1000, and 5000 times as great as that of etidronate,
twice daily). 315 Calcitonin is listed as an antidote on respectively. 191 Ibandronate is approximately 5000 times