Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study.

BACKGROUND: Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions. PATIENTS AND METHODS: For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates). RESULTS: At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients. CONCLUSIONS: Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions.

The bisphosphonate ibandronate accelerates osseointegration of hydroxyapatite-coated cementless implants in an animal model.

BACKGROUND: There is evidence that bisphosphonates can improve fixation of cementless metal implants by enhancing the extent of osseointegration. The current preclinical study examined whether the nitrogen-containing bisphosphonate ibandronate can accelerate this process, resulting in early achievement of secondary stability and sealing of the bone-implant interface to prevent wear debris migration. METHODS: The study was conducted on 88 female Sprague-Dawley rats in which uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the medullary canal of each femur. The animals were randomly assigned to receive subcutaneous treatment with 1.0, 2.5, or 5.0 microg/kg per day ibandronate or saline solution as a control. The extent of osseointegration expressed by the osseointegrated implant surface was quantified by histomorphometry at eleven time points during the study period. To determine the time course of osseointegration, the data were expressed using third-order polynomial regression analysis. RESULTS: For hydroxyapatite-coated implants, the highest dose of ibandronate (5 microg) reduced the time for a sufficient implant fixation of 60% osseointegrated implant surface to 18 days compared to 38 days in the control group. This reduction of 20 days (52.6%) represents a halving in the time required for sufficient osseointegration of the implant. For hydroxyapatite-coated implants and low-dose ibandronate application (1 microg, 2.5 microg) and for uncoated titanium implants, acceleration of osseointegration was not observed in any of the study arms. CONCLUSION: Continuous treatment with 5 microg/kg per day ibandronate is potent in accelerating osseointegration of hydroxyapatite-coated implants. As a result, improved early secondary stability and prevention of wear debris migration by the sealing of the implant-bone interface can be expected, therefore prolonging the long-term survival of the implant.

Osseointegration of cementless implants with different bisphosphonate regimens.

Some evidence suggests a daily dose of bisphosphonates improves fixation of cementless metal implants by enhancing osseointegration. Because the necessity of daily administration may result in suboptimal adherence to therapy, single- dose administration is desirable. We examined whether a dose-equivalent single injection of the nitrogen-containing bisphosphonate ibandronate is as effective as a daily injection in improving the osseointegrated surface and enhancing periprosthetic bone mineralization (bone volume to tissue volume) of cementless metal implants. Uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the femoral medullary canal of 55 female Sprague Dawley rats. The animals were randomly assigned subcutaneous treatments with 25 microg/kg body weight ibandronate per day, a dose-equivalent single injection of 28 x 25 microg/kg body weight, or saline solution for control. Histomorphometric evaluation revealed an enhanced osseointegrated surface for hydroxyapatite-coated implants in both treatment groups, but only for daily injections for uncoated titanium implants. Bone volume to tissue volume was improved in both treatment groups. Our results suggest that an equivalent-dose single injection of ibandronate is as effective as a daily dose in improving osseointegration and stabilization of hydroxyapatite-coated titanium implants in this rat model.

High dosage treatment of nitrogen-containing bisphosphonate ibandronate is required for osseointegration of cementless metal implants.

BACKGROUND: There is evidence that application of a bisphosphonate can improve fixation of cementless metal implants by enhancing the extent of osseointegration, but the required dose regimen is still under discussion. The current preclinical study was designed to determine the optimal treatment dose of the nitrogen-containing bisphosphonate ibandronate to improve osseointegration of cementless metal implants. METHODS: The study was conducted in 52 female Sprague-Dawley rats in which uncoated and hydroxyapatite-coated titanium implants were surgically inserted into the medullary canal of each femur. The animals were randomly assigned to receive subcutaneous treatment with ibandronate 1 microg/kg body weight (osteoporosis dose) or 25 microg/kg (tumor dose) per day or saline solution for control. RESULTS: Histomorphometric evaluation revealed a significant enhanced extent of osseointegrated implant surface in the high-dose treatment group for both implants compared to the low-dose group and the control group. No significant differences were observed between the two implants in any group. CONCLUSIONS: The results of the present study indicate that improved osseointegration of hydroxyapatite-coated and uncoated titanium implants is dose-dependent and requires high-dose application of bisphosphonate ibandronate equivalent to that needed to treat patients with tumor disease. Lower doses equivalent to those for treatment of osteoporosis showed no beneficial effect.