Tolerability of intravenous pamidronate for the treatment of osteoporosis and other metabolic osteopathies: A retrospective analysis.

BACKGROUND: Intravenous disodium pamidronate has been described in the treatment of several osteopathies. Although tolerability has been found to be good in clinical trials, some mild to serious adverse events (AEs) have been reported.
OBJECTIVES: The aims of this study were to analyze the toelrability of IV pamidronate in patients being treated for osteoporosis and other metabolic osteopathies and to describe particular patients with relative contraindications, because such cases are not commonly seen in daily clinical practice.
METHODS: We performed a retrospective analysis of patients with different osteopathies who were administered IV infusions of pamidronate at doses ranging from 15 to 90 mg/infusion and 15 to 900 mg/year. The study was conducted in patients who had received treatment at the Institute of Metabolic Investigations, University of Salvador, Buenos Aires, Argentina, between January 1995 and December 2003. To rule out dose-related AEs, a comparison was made between patients who received fewer IV infusions and had cumulative doses of 120 to 180 mg/y (less frequent administration [LFA] group) and those patients who received regular infusions and had cumulative doses of >180 mg/year (frequent administration [FA] group). To confirm data obtained from medical records and to assess the occurrence of AEs, attempts were made to interview all patients by phone. The following information was verified for each patient included in the study: the reason for treatment, documented evidence of current diagnostic criteria, and whether the dose administered was adequate to treat the patient's condition.
RESULTS: Six hundred eight patients (464 [76.3%]women, 144 [23.7%]men; mean [SD] age, 69 [10] years) with various osteopathies (osteoporosis, 367 [60.4%] of the patients; Paget's disease, 172 [28.3%]; Sudeck's disease, 63 [10.4%]; multiple myeloma, 3 [0.5%]; and bone metastases, 3 [0.5%]) were administered a total of 2933 IV infusions of pamidronate during the study period. We were able to confirm the clinical records of 69.4% (422/608) of the patients by telephone survey; 29.9% (124/415) of those patients experienced extraskeletal AEs (most commonly fever and flu-like symptoms [eg, headache, malaise, fatigue, chills, and asthenia]). The percentage of patients reporting AEs was significantly higher for the LFA group than that of the FA group (91.2 vs 19.5; P < 0.001), although factors other than the frequency of treatment might have had a bearing on this finding. All AEs were mild and transient in both groups of patients, and there were no reports of jaw osteonecrosis in either group. It should be noted that although LFA patients received lower doses of pamidronate per infusion than the FA group, they had higher cumulative doses/year. Biochemical variables for the entire study population were compared with baseline measurements, and no significant changes in mean values were observed. Both serum calcium and 25-hydroxy vitamin D levels remained within normal ranges. On the other hand, there was a transient decrease in white blood cell count (WBCC) in 73 (12.0%) patients, and leukopenia was observed in 8 (1.3%) patients. However, 5 of the 6 patients who were leukopenic at the beginning of treatment had normal WBCCs during follow-up. Platelet count decreased significantly in 20 (3.3%) patients, and 5 (0.8%) patients developed thrombocytopenia. Serum creatinine (sCreat) levels increased significantly in 91 (15.0%) patients. This increase was transient and within normal limits (0.6-1.2 mg/dL) in 79 (86.8%) of those patients but persistent in the other 12 (13.2%), all of whom received higher doses of pamidronate or had other risk factors for renal failure such as advanced age, diabetes, multiple myeloma, or an obstructor disease. Baseline sCreat level for 7 of these 12 patients was >1.20 mg/dL.
CONCLUSIONS: Pamidronate administered IV was well tolerated when used for treating osteoporosis or other metabolic osteopathies in our study population. The clinical AEs observed with IV pamidronate administration were not serious and hematologic changes were mild, transient, and not associated with dose, time of treatment, or any particular underlying disease. An increase in sCreat level was the most frequent biochemical complication and was found in patients with additional risk factors for renal failure and particular diseases. Whether certain patients with risk factors for osteoporosis may require even fewer IV administrations of the drug is an issue that remains to be elucidated.