Impending spinal cord compression and vertebral fractures are considered contraindications for radionuclide bone pain palliation therapy. However, most of the patients with widespread bone metastases already have weakened vertebral segments that may be broken. Therefore, local field external-beam radiotherapy or percutaneous vertebroplasty (VP) should be considered to improve the patient's quality of life and to institute subsequent appropriate treatment, including radionuclide therapy for bone pain palliation. The objective of this study was to develop a strategy for an effective treatment of bone metastases in patients with widespread bone metastases and intolerable pain, associated with impending cord compression or vertebral fractures. Eleven patients (5 females and 6 males, aged 32-62 years; mean age 53.8 ± 2.7 years) with multiple skeletal metastases from carcinomas of prostate (n = 3), breast (n = 3) and lung (n = 5) were studied. Their mean pain score measured on a visual analogue scale of 10 was found to be 8.64 ± 0.15 (range 8-9) and the mean number of levels with impending cord compression or vertebral fracture was 2.64 ± 0.34 (range 1–4). All patients underwent vertebroplasty and after 3–7 days received Sm-153 ethylene diamine tetra methylene phosphonic acid (EDTMP) therapy. Sm-153 EDTMP was administered according to the recommended standard bone palliation dose of 37 MBq/kg body weight. Whole body (WB) bone scan, computed tomography and magnetic resonance imaging (MRI) were performed before and after treatment in all patients. Pain relief due to stabilization of vertebrae after VP occurred within the first 12 hours (mean 4.8 ± 1.2 hours; range 0.5–12 hours), and the mean pain score was reduced to 4.36 ± 0.39 (range 2–6). Subsequent to Sm-153 EDTMP treatment, further pain relief occurred after 3.91 ± 0.39 days (range 2-6 days) and the pain score decreased to 0.55 ± 0.21 (range 0–2). The responses to treatment were found to be statistically significant (P < 0.0001). Based on the results on this limited patient population, we conclude that spinal stabilization using VP in patients with widespread bone metastases and impending cord compression is an effective way to decrease disability with pain and to facilitate subsequent systemic palliation of painful skeletal metastases by Sm-153 EDTMP therapy.

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered to all patients at the standard bone palliation dose of 37 MBq/kg body weight. All patients received Zoledronic acid before and after treatment in standard dosage of 4 mg every 28 days. WB bone scan, CT, and MRI were performed before treatment in all patients to exclude cord compression and vertebral fractures. Pain scores and quality of life (QOL) measurements were recorded meticulously in all patients. In groups I, II, and III, pain relief occurred in 10.4 ± 3.1 (Range = 5-15); 3.1 ± 1.1 (Range = 1-5) and 22 ± 5.1 (Range = 15-35) days, respectively, following radionuclide therapy. There was statistically significant difference between pain score in all groups before and after treatment as well as statistically significant difference in time to pain relief onset between Group II and other groups of patients (P < 0.0001). Based on our results we concluded that administration of Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment helps in achieving better pain relief, as well as at the shortest time interval from the start of therapy.

Breast and prostate cancer have a propensity to metastasize to bones and cause osteolysis and abnormal new bone formation. Metastases locally disrupt normal bone remodeling. Although metastases from prostate cancer have been classified as osteoblastic based on the radiographic appearance of the lesion, data gleaned from a rapid autopsy program indicate that the same prostate cancer patient may have evidence of both osteolytic and osteoblastic disease as shown by histologic examinations. Thus, bone metastases are heterogeneous, requiring combined treatment targeting on both osteolytic and osteoblastic lesions. While Samarium-153 (Sm-153) oxabifore treatment is widely used for the relief of pain in patients with osteoblastic metastatic bone lesions, Xgeva (Denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. It is a fully human monoclonal antibody that has been designed to target receptor activator of nuclear factor-kB ligand (RANKL), a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. The main objectives of the current pilot study were to estimate the effectiveness of bone metastases treatment by a combination of Sm-153 oxabifore and Xgeva (Denosumab). Five patients (four female and one male, aged 35-64, mean age 50.8) with multiple skeletal metastases from prostatic carcinoma (1) and breast carcinoma (4) were studied. Their mean objective pain score according to visual analog scoring system on a 1-10 scoring system was 7.8 ± 0.5 (range 6-9). Sm-153 oxabifore was administered at the standard bone palliation dose of 37 MBq/kg body weight. Xgeva (Denosumab) was administered at a dosage of 120 mg every 4 weeks, with the monitoring of calcium level and administration of calcium, magnesium, and vitamin D. Whole body (WB) bone scan was performed before and 3 months after treatment in all patients. After Sm-153 oxabifore administration, pain relief occurred within 4.4 ± 1.25 days (range 2-9 days) and the objective pain score decreased to 0.2 ± 0.2 (range 0-1). There was statistically significant difference found, according to the pain score system, before and after treatment (P < 0.0001). WB bone scan showed that in one patient, there was significant reduction in the number and intensity of bone metastases, and in four patients, there was no evidence of bone metastases found. Based on our first experience, combined treatment of bone metastases with Sm-153 oxabifore and Denosumab is effective and safe.