3.4.6 Bisphosphonates and Calcitonin
Severe bone pain is a frequent complication of bone metastases. For example,
Galasko (1972) reported that 65 percent of patients with bone metastases from
breast cancer experience bone pain. Bone pain is probably caused by
osteoclast-induced bone resorption by the tumor, which may also result in
osteoporosis, hypercalcemia, microfractures, or pathologic fractures (Ascari,
Attardo-Parrinello, and Merlini, 1989). Bisphosphonates (e.g., etidronate,
pamidronate) are analogues of endogenous pyrophosphates, which inhibit bone
resorption in viva (Fleish, Russel, and Francis, 1969). Pamidronate and
etidronate are currently available for the management of hypercalcemia
associated with malignancy. Anecdotal reports and early clinical trials have
reported relief of bone pain or decreased analgesic use after the initiation of
a bisphosphonate (Delmas, Charhon, Chapuy, et al., 1982; Elomma, Blomqvist,
Grohm, et al., 1983). Other researchers have described similar findings with
bisphosphonates that are not available in the United States
(Attardo-Parrinello, Merlini, Pavesi, et al., 1987; van Hotenverzantvoort,
Zwinderman, Aaronson, et al., 1991). Smith (1989), however, reported no
difference in symptomatic relief or analgesic requirements in 57 patients with
advanced hormone-refractory prostate cancer treated with etidronate or
placebo.
Calcitonin is also a potent inhibitor of osteoclast-induced bone resorption
and, like the bisphosphonates, is used in the management of hypercalcemia of
malignancy. At least one double-blind, randomized trial comparing salmon
calcitonin to placebo demonstrated that 100 IU/day subcutaneously resulted in
reduced analgesic consumption, shorter duration of pain, and subjective
improvement (Roth and Kolaric, 1986).
Although these agents that inhibit bone resorption appear to be beneficial in
some patients with painful bone metastases, other patients have failed to
respond. Additional studies are warranted to define criteria that may predict a
clinical response to these drugs and to define further their optimal use in
this setting.
Administration Methods
Oral
Rectal
Intraventricular
Patient-Controlled Analgesia (PCA)
Adjuvant Drugs
Corticosteroids
Hydroxyzine
Index