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Reduced bone pain by intensive bisphosphonate-therapy of new diagnosed bone metastases
ABSTRACTS / Bone 38 (2006) S65 – S87
87 Local treatment of giant cell tumors by a bone substitute material and a bisphosphonate A.A. Kurth , B. Habermann, M. Salzmann, C. Eberhardt Department of Orthopaedic Surgery, University Hospital Frankfurt, Marienburgstr. 2, 60528 Frankfurt Surgical dissection like curettage including refilling with bone cement (‘‘Palacos plumb’’) is the standard therapy of relapsing giant cell tumours. Despite subtle intralesional resection and curettage tumour relapse accompanied by further bone destruction may appear.Many adjuvant topical therapies like phenol, hydrogenperoxidase or liquid nitrogen were used as a local control after intralesional resection of tumours. A specific adjuvant therapy targeted directly towards the tumor-biology (osteoclasts and giant cell tumours) has not yet been described. Bisphosphonates inhibit osteoclastic bone resorption and osteoclastogenesis. The functional and immuno-histochemical analogy between osteoclasts and polynuclear giant cells in giant cell tumors suggests acting bisphosphonates in giant cell tumour cells like in osteoclasts. Material: Since beginning of 2004 three patients were medicated in our clinic with local application of ibandronate after intralesional curettage of a giant cell tumour. The so developed cavity was refilled with bone substitute material (CalcibonR, Biomet). This (approximately 100 CC) was saturated with 20 mg ibandronate before. The saturated bone substitute material was inserted into the cavity and impacted. Patients were subjected to roentgenography in regular intervals of 3 month. After follow-up examinations at an average of 12 month no indication of giant cell tumours-relapses or a bone substitute resorption were found. Radiologically or clinically no negative effect of local bisphosphonate-therapy appeared on the material integration or fracture recovery. Discussion: The local adjuvant therapy of giant cell tumors with a bisphosphonate and bone substitute material based on preclinical results and first clinical experiences can be seen as an alternative to well established procedures. This approach shows great promise for patients in the quantity of surgery interventions, relapse frequency, morbidity and mortality. Further clinical application on this tumour should be investigated in the context of a multi-center study. doi:10.1016/j.bone.2006.01.033
88 Reduced bone pain by intensive bisphosphonate-therapy of new diagnosed bone metastases A.A. Kurth , M. Pilz, U. Stumpf, A. Mu¨ller, C. Eberhardt Department of Orthopaedic Surgery, University Hospital Frankfurt Marienburgstr. 2, 60528 Frankfurt Introduction: Bone metastases are associated to severe bone pain and are often the first symptoms of an already long-time tumor disease. In many cases the standard pain therapy is not sufficient and side effects are severe. In clinical studies bispho-
S77
sphonates caused good pain reduction by standard dosage and a longer observation period. Particularly in the first weeks of bone metastasis it is necessary to reduce pain and to keep quality of life and the courage of patients. Methods: 11 patients with new osteolytic bone tumor diseases (8 breast cancers, 2 pulmonary cancers, 1 kidney cancer) and bone pain were applied to intensive dosage of ibandronate after diagnosis of bone metastases. 6 mg ibandronate i.v. for 1h was infused every 24 hours for 3 days. All patients were bisphosphonateuntreated and obtained a symptomatic pain therapy (NSAR, analgesic, opioids) up to this point. Patients rated their bone pain severity daily subjectively on a visual analog scale (VAS) from 0 (no pain) to 10 (maximal pain); within 3 weeks patients were admitted to further therapy (e.g. radiation, operation, chemotherapy). Results: A short term high dosed bisphosphonate-therapy reduced significantly within the first 5 to 7 days pain caused by bone metastases (VAS day 0: 6– 7, day 7: 3– 4). Increased pain medication was not observed. Discussion: This small clinical pilot study about an intensive high dosed bisphosphonate-therapy within the first days after diagnosis of bone metastases showed an impressive reduction of bone pain in a short time period. This scheme intensifies the already proved analgesic effect of bisphosphonates, probably due to suppressing the pathological processes of osteoclast-associated bone-destruction. Based on these results this concept should be verified in a controlled clinical study. doi:10.1016/j.bone.2006.01.034
89 Pain reduction with oral and intravenous ibandronate treatment for metastatic bone disease of breast cancer A.A. Kurth , J. Seraphin, F. Schu¨tze, A. Nusch, I. Scha¨fer, H. Meden Department of Orthopaedic Surgery, University Hospital Frankfurt Marienburgstr. 2, 60528 Frankfurt Bone metastases cause considerable impairment due to pain and skeletal complications in breast cancer patients. Therefore the effect of BondronatR, a third-generation aminobisphosphonate, on pain reduction was assessed. Patients and methods: 551 patients (aged 62.8 T 11.9 years) were evaluated in an open label study. 63% were in PD or first diagnosed of breast cancer, 29% showed SD, and 7% were in remission. 46% of the patients suffered from bone metases, 8% presented additional local, and 34% additional distant metastases. 12% both were reported. Most of the patients had various pretreatments including bisphosphonates. Patients were treated with 6 mg BondronatR i.v. every 4 weeks (86%) or 50 mg p.o daily (11%). Results: Patient suffering from pain at study entry were asssessed with the VAS scale from 0 to 10. The mean value was 3.4 T 2.5 SD over all, but definitely lower in the patient group with ibandronate pretreatment (2.1 T 2.2). The use of analgetics confirmed these findings. 73% of the patient improved during therapy, 10% reported no changes, whereas 17% worsened despite treatment. Patients without biphosphonate pretreatment
87 Local treatment of giant cell tumors by a bone substitute material and a bisphosphonate A.A. Kurth , B. Habermann, M. Salzmann, C. Eberhardt Department of Orthopaedic Surgery, University Hospital Frankfurt, Marienburgstr. 2, 60528 Frankfurt Surgical dissection like curettage including refilling with bone cement (‘‘Palacos plumb’’) is the standard therapy of relapsing giant cell tumours. Despite subtle intralesional resection and curettage tumour relapse accompanied by further bone destruction may appear.Many adjuvant topical therapies like phenol, hydrogenperoxidase or liquid nitrogen were used as a local control after intralesional resection of tumours. A specific adjuvant therapy targeted directly towards the tumor-biology (osteoclasts and giant cell tumours) has not yet been described. Bisphosphonates inhibit osteoclastic bone resorption and osteoclastogenesis. The functional and immuno-histochemical analogy between osteoclasts and polynuclear giant cells in giant cell tumors suggests acting bisphosphonates in giant cell tumour cells like in osteoclasts. Material: Since beginning of 2004 three patients were medicated in our clinic with local application of ibandronate after intralesional curettage of a giant cell tumour. The so developed cavity was refilled with bone substitute material (CalcibonR, Biomet). This (approximately 100 CC) was saturated with 20 mg ibandronate before. The saturated bone substitute material was inserted into the cavity and impacted. Patients were subjected to roentgenography in regular intervals of 3 month. After follow-up examinations at an average of 12 month no indication of giant cell tumours-relapses or a bone substitute resorption were found. Radiologically or clinically no negative effect of local bisphosphonate-therapy appeared on the material integration or fracture recovery. Discussion: The local adjuvant therapy of giant cell tumors with a bisphosphonate and bone substitute material based on preclinical results and first clinical experiences can be seen as an alternative to well established procedures. This approach shows great promise for patients in the quantity of surgery interventions, relapse frequency, morbidity and mortality. Further clinical application on this tumour should be investigated in the context of a multi-center study. doi:10.1016/j.bone.2006.01.033
88 Reduced bone pain by intensive bisphosphonate-therapy of new diagnosed bone metastases A.A. Kurth , M. Pilz, U. Stumpf, A. Mu¨ller, C. Eberhardt Department of Orthopaedic Surgery, University Hospital Frankfurt Marienburgstr. 2, 60528 Frankfurt Introduction: Bone metastases are associated to severe bone pain and are often the first symptoms of an already long-time tumor disease. In many cases the standard pain therapy is not sufficient and side effects are severe. In clinical studies bispho-
S77
sphonates caused good pain reduction by standard dosage and a longer observation period. Particularly in the first weeks of bone metastasis it is necessary to reduce pain and to keep quality of life and the courage of patients. Methods: 11 patients with new osteolytic bone tumor diseases (8 breast cancers, 2 pulmonary cancers, 1 kidney cancer) and bone pain were applied to intensive dosage of ibandronate after diagnosis of bone metastases. 6 mg ibandronate i.v. for 1h was infused every 24 hours for 3 days. All patients were bisphosphonateuntreated and obtained a symptomatic pain therapy (NSAR, analgesic, opioids) up to this point. Patients rated their bone pain severity daily subjectively on a visual analog scale (VAS) from 0 (no pain) to 10 (maximal pain); within 3 weeks patients were admitted to further therapy (e.g. radiation, operation, chemotherapy). Results: A short term high dosed bisphosphonate-therapy reduced significantly within the first 5 to 7 days pain caused by bone metastases (VAS day 0: 6– 7, day 7: 3– 4). Increased pain medication was not observed. Discussion: This small clinical pilot study about an intensive high dosed bisphosphonate-therapy within the first days after diagnosis of bone metastases showed an impressive reduction of bone pain in a short time period. This scheme intensifies the already proved analgesic effect of bisphosphonates, probably due to suppressing the pathological processes of osteoclast-associated bone-destruction. Based on these results this concept should be verified in a controlled clinical study. doi:10.1016/j.bone.2006.01.034
89 Pain reduction with oral and intravenous ibandronate treatment for metastatic bone disease of breast cancer A.A. Kurth , J. Seraphin, F. Schu¨tze, A. Nusch, I. Scha¨fer, H. Meden Department of Orthopaedic Surgery, University Hospital Frankfurt Marienburgstr. 2, 60528 Frankfurt Bone metastases cause considerable impairment due to pain and skeletal complications in breast cancer patients. Therefore the effect of BondronatR, a third-generation aminobisphosphonate, on pain reduction was assessed. Patients and methods: 551 patients (aged 62.8 T 11.9 years) were evaluated in an open label study. 63% were in PD or first diagnosed of breast cancer, 29% showed SD, and 7% were in remission. 46% of the patients suffered from bone metases, 8% presented additional local, and 34% additional distant metastases. 12% both were reported. Most of the patients had various pretreatments including bisphosphonates. Patients were treated with 6 mg BondronatR i.v. every 4 weeks (86%) or 50 mg p.o daily (11%). Results: Patient suffering from pain at study entry were asssessed with the VAS scale from 0 to 10. The mean value was 3.4 T 2.5 SD over all, but definitely lower in the patient group with ibandronate pretreatment (2.1 T 2.2). The use of analgetics confirmed these findings. 73% of the patient improved during therapy, 10% reported no changes, whereas 17% worsened despite treatment. Patients without biphosphonate pretreatment