Bone disease in myeloma

The major clinical manifestation of multiple myeloma results from osteolytic bone destruction. The only currently Food and Drug Administration-approved drug for the treatment of the bony complications of multiple myeloma is monthly intravenous pamidronate at a dose of 90 mg infused over 4 hours. Recent studies have shown the safety of 2-hour infusions. A randomized trial comparing pamidronate to placebo continued to show benefits throughout the 21-month trial. Although the duration of therapy has not been firmly determined, it is likely that discontinuation of this drug will be met by enhanced bone loss and an increased risk of bony complications for these patients. Thus, it is recommended that the drug be continued indefinitely. Support for this recommendation also comes from the reduced bone density observed in women with postmenopausal osteoporosis following the withdrawal of bisphosphonate treatment. Recent attempts to give higher doses, more frequent infusions (every 2 weeks or less), or more rapid infusions (1 hour or less) of pamidronate have occasionally been associated with albuminuria and azotemia. These modifications should therefore be avoided. Importantly, the drug can be safely administered at 90 mg monthly to patients with poor renal function. The use of pamidronate for myeloma patients without lytic bone involvement or with Durie-Salmon stages I or II disease has not been evaluated. However, it is recognized that most patients with earlier stages of disease or without lytic bone involvement also develop bony complications. There is no reason to believe that these patients would not benefit from monthly intravenous infusions of pamidronate. The potential antimyeloma effect of this agent is another reason to administer this drug in these types of patients. Thus, it is our practice to administer monthly pamidronate to myeloma patients regardless of stage or bone involvement. However, trials evaluating oral bisphosphonates have produced inconsistent clinical results, probably as a result of the erratic and scanty poor absorption as well as poor oral tolerability of these drugs. Although these oral agents may be useful in some patients, it is impossible to identify which myeloma patients will benefit from orally administered bisphosphonates. The more potent nitrogen-containing bisphosphonate zoledronic acid more effectively reverses hypercalcemia of malignancy than pamidronate, and it appears promising in reducing bone loss in cancer patients. However, its efficacy in preventing skeletal complications is still being evaluated. Many other types of new agents are in early clinical trials, but their efficacy remains unproven at the present time.