• 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • BMS-387032 Data for each assessment point


    Data for each assessment point are expressed as the mean value plus standard deviation. One tailed paired t-tests were performed to analyze the effects of ibandronate treatment. Significance level was set at p<0.05.
    Results The study included 33 patients with a variety of different primary tumors (Table 1). The median age of patients was 59 years (33–78 yrs). The median duration of inpatient hospitalization before starting therapy was 1 day (0–2 days). All patients remained hospitalized until they were transferred to further treatment modalities (e.g. surgery, chemotherapy, radiation) with a median stay of 9 days (range 7–10 days). At BMS-387032 day 0, all patients enrolled in the study were experiencing severe bone pain (mean visual analog pain score 6.8 (6–8)) while receiving an equivalent of 400mg/d oral morphine. Pain intensity significantly decreased on day 3–5 (mean VAS 4.9 (3–7)) (p<0.01) and day 5–7 (mean VAS 3.7 (2–7)) (p<0.01) compared to day (mean VAS 6.8 (6–8)) (Fig. 1). Significant reductions from baseline in visual analog pain scores while receiving ibandronate were not based on an increased use of other analgetics. None of the patients showed an increase in MEDD index throughout the study BMS-387032 (Fig. 2). Only one patient not responding to Ibandronate needed additional analgesic measures with regularly used fentanyl patches. Side effects consisted mainly of fever on the day following the first intravenous application of Ibandronate in 9 patients. One patient experienced a flu-like syndrome (fever, myalgia) that lasted for 48h. No therapy was discontinued due to adverse side effects. Renal function and serum calcium levels (medium serum Calcium of 9.2mg/dl at day (range: 8.3 to 10.1), medium serum Calcium of 8.8mg/dl at day 7 (range 8.1–9.9)) were in the physiological range in every measurement.
    Discussion In the current study, we were able to show that the administration of loading-dose Ibandronate therapy (60mg Ibandronate infused intravenously over 1h for 3 consecutive days) resulted in a highly significant decrease in pain levels in patients suffering from metastatic bone disease. Pain reduction was rapidly seen, within 3–5 days after the first infusion and accompanied by a substantial reduction in analgesic use.
    Ethical approval
    Informed consent
    Conflict of interest
    Introduction High-grade osteosarcoma is an aggressive primary malignant bone tumor that is associated with a relatively good outcome; since pre-operative and adjuvant combination chemotherapy has been introduced the survival rate at 5 years for the non-metastatic form at diagnosis has been 50–70% [1,2]. Osteosarcoma treatment comprises surgical excision with wide resection of the tumor after neo adjuvant chemotherapy. Adjuvant chemotherapy is then adapted to histological response [3]. Concerning surgical techniques, limb sparing is currently the preferred option. Reconstruction is dependent on resection site: if epiphysis cannot be preserved, mega prosthesis sometimes associated with an allograft is typically used [4]. Otherwise, different conservative techniques are described: massive autograft [5], vascularized autograft sometimes associated with allograft or isolated allograft [6–8]. A permanent remission from osteosarcoma can be anticipated after 10 years of event free survival [9–13], where after the primary challenge is to ameliorate the quality of life of patients suffering from physical and aesthetic defects caused by tumor resection. For recovery of damaged soft tissues, plastic and reconstructive surgery includes autologous grafts of adipose tissue. Regenerative medicine promises new alternatives through the use of mesenchymal stem cells (MSCs), which are bone marrow-resident and multipotent cells. They have been originally identified as a source of bone progenitor cells, but they also differentiate into adipocytes, chondrocytes and myoblasts. Human MSCs may be combined with scaffolds to increase bone healing as reported previously [10,12]. Moreover, the use of MSCs cultured from bone marrow to supplement an osteoarticular allograft in patients treated after bone tumor resection did not increase the risk of local tumor recurrence compared to control populations. Additionally, MSCs can be modified to express tumor-targeted agents [14,15] and used as “mesenkillers” [16].