ted by concurrent excessive bone repair, affecting one or more bones. These changes result in thickened but weakened bones that may fracture or bend under stress. Signs and symptoms may be bone pain, deformity, fractures, neurological disorders resulting from cranial and spinal nerve entrapment and from spinal cord and brain stem compression, increased cardiac output to the involved bone, increased serum alkaline phosphatase levels (reflecting increased bone formation) and/or urine hydroxyproline excretion (reflecting increased bone resorption).
Clinical Trials
In one double-blind clinical trial, 64 patients with moderate to severe Paget’s disease of bone were enrolled to receive 5 mg, 15 mg, or 30 mg of pamidronate disodium as a single 4 hour infusion on 3 consecutive days, for total doses of 15 mg, 45 mg, and 90 mg of pamidronate disodium.
The mean baseline serum alkaline phosphatase levels were 1409 U/L, 983 U/L, and 1085 U/L, and the mean baseline urine hydroxyproline/creatinine ratios were 0.25, 0.19, and 0.19 for the 15 mg, 45 mg, and 90 mg groups, respectively.
The effects of pamidronate disodium on serum alkaline phosphatase (SAP) and urine hydroxyproline/creatinine ratios (UOHP/C) are summarized in the following table.
Percent of Patients With Significant % Decrease in SAP and UOHP/C SAP
UOHP/C
% Decrease
15 mg
45 mg
90 mg
15 mg
45 mg
90 mg
≥50
26
33
60
15
47
72
≥30
40
65
83
35
57
85
The median maximum percent decreases from baseline in serum alkaline phosphatase and urine hydroxyproline/creatinine ratios were 25%, 41%, and 57%, and 25%, 47%, and 61% for the 15 mg, 45 mg, and 90 mg groups, respectively. The median time to response (≥50% decrease) for serum alkaline phosphatase was approximately 1 month for the 90 mg group, and the response duration ranged from 1 to 372 days.
No statistically significant differences between treatment groups, or statistically significant changes from baseline were observed for the bone pain response, mobility, and global eva luation in the 45 mg and 90 mg groups. Improvement in radiologic lesions occurred in some patients in the 90 mg group.
Twenty-five patients who had Paget’s disease were retreated with 90 mg of pamidronate disodium. Of these, 44% had a ≥50% decrease in serum alkaline phosphatase from baseline after treatment, and 39% had a ≥50% decrease in urine hydroxyproline/creatinine ratio from baseline after treatment.
Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma
Osteolytic bone metastases commonly occur in patients with multiple myeloma or breast cancer. These cancers demonstrate a phenomenon known as osteotropism, meaning they possess an extraordinary affinity for bone. The distribution of osteolytic bone metastases in these cancers is predominantly in the axial skeleton, particularly the spine, pelvis, and ribs, rather than the appendicular skeleton, although lesions in the proximal femur and humerus are not uncommon. This distribution is similar to the red bone marrow in which slow blood flow possibly assists attachment of metastatic cells. The surface-to-volume ratio of trabecular bone is much higher than cortical bone, and therefore disease proc
