Pamidronate Protects Bone
ABSTRACT & COMMENTARY
Synopsis: Pamidronate protects against fractures and bone pain associated with metastatic breast cancer.
Source: Hortobagyi GN, et al. N Engl J Med 1996;335:1785-1791.
Hortobagyi et al from the university of texas M.D. Anderson Cancer Center in Houston studied the effect of pamidronate in a randomized, placebo-controlled trial with 382 metastatic (osteolytic lesions) breast cancer patients receiving cytotoxic chemotherapy. Pamidronate was administered as 90 mg given in 250 mL of an intravenous infusion over two hours, every three or four weeks. Pamidronate treatment delayed the onset and reduced the incidence of skeletal complications. In contrast to the placebo group, which had progressive worsening of bone pain, the treated group had decreases from base line in bone pain. There were no serious side effects associated with pamidronate treatment.
COMMENT BY LEON SPEROFF, MD
I chose this article for review, not because of the dramatic impact of pamidronate against bone problems associated with metastatic breast cancer, but to highlight the availability of another bisphosphonate. There is no doubt that bisphosphonates are potent inhibitors of osteoclastic bone resorption and have the following effects: increase in bone density, decrease of fractures associated with osteoporosis, and reductions in hypercalcemia and bone complications associated with cancer.
I am frequently asked how the bisphosphonates compare with estrogen. The clinical trial comparing alendronate and estrogen is not yet finished. Based on data with etidronate, it is expected that the bisphosphonates produce about the same impact as estrogen on bone, and that there will be a mild synergistic effect on bone density when the two are combined. (However, it is not known whether this effect is clinically significant in terms of fracture risk.) Because the bisphosphonates are incorporated into the bone, and very long-term follow-up data are not yet available, there is hesitancy to recommend bisphosphonates for long-term prophylactic treatment to prevent osteoporosis.
A major problem with alendronate is the requirement for early morning administration to a fasting stomach followed by the need to remain standing in order to avoid esophagitis and upper gastrointestinal reactions. Clinical trials found a low incidence of problems and no differences between treated and placebo groups. However, in real life, people don’t perform the same as individuals in clinical trials. The side effect rate has been significant, and occasional individual reactions have been severe. An intravenous route of administration avoids this problem, and a monthly office treatment (that can be made swiftly without the prolonged use of an intravenous solution) would be an attractive option for many patients.
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