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Skeletal Complications (skeletal + complications)
Selected AbstractsMy aching bones: Skeletal complications of acute lymphoblastic leukemiaPEDIATRIC BLOOD & CANCER, Issue 1 2006James B. Nachman MDArticle first published online: 31 OCT 200 No abstract is available for this article. [source] Pharmacologic profile of zoledronic acid: A highly potent inhibitor of bone resorptionDRUG DEVELOPMENT RESEARCH, Issue 4 2002Jonathan R. Green Abstract Bisphosphonates are effective in treating benign and malignant skeletal diseases characterized by enhanced osteoclastic bone resorption (i.e., osteoporosis, Paget's disease, tumor-induced osteolysis). The nitrogen-containing bisphosphonate pamidronate is currently the standard treatment for hypercalcemia of malignancy (HCM) and skeletal complications of bone metastases. Zoledronic acid, a novel nitrogen-containing bisphosphonate with an imidazole substituent, has demonstrated more potent inhibition of osteoclast-mediated bone resorption than all other bisphosphonates, including pamidronate, in both in vitro and in vivo preclinical models. Zoledronic acid inhibited ovariectomy-induced bone loss in adult monkeys and rats, and long-term treatment prevented skeletal turnover and subsequent bone loss, reduced cortical porosity, and increased mechanical strength. Zoledronic acid also significantly inhibited bone loss associated with arthritis, bone metastases, and prosthesis loosening. The increased potency of zoledronic acid vs. pamidronate has been demonstrated clinically: zoledronic acid (4 or 8 mg iv) was superior to pamidronate (90 mg iv) in normalizing corrected serum calcium in patients with HCM. In patients with bone metastases, low doses of zoledronic acid (, 2 mg) suppressed bone resorption markers , 50% below baseline, whereas pamidronate 90 mg yielded only 20 to 30% suppression. Importantly, the increased potency of zoledronic acid is not associated with an increased incidence of local (bone) or systemic adverse events. Zoledronic acid does not impair bone mineralization and, compared with pamidronate, has a greater renal and intestinal tolerability therapeutic index. Thus, based on preclinical assays and clinical data, zoledronic acid is the most potent bisphosphonate tested to date. Given its potency and excellent safety profile, zoledronic acid is now poised to become the new standard of treatment for HCM and metastatic bone disease. Drug Dev. Res. 55:210,224, 2002. © 2002 Wiley-Liss, Inc. [source] Oral sodium clodronate induced osteonecrosis of the jaw in a patient with myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007Amir H Montazeri Abstract Bisphosphonate therapy has been shown to significantly reduce the incidence of skeletal complications in patients with myeloma. Several recent reports have described osteonecrosis of the jaw (ONJ) associated with bisphosphonates. These reports mainly demonstrate an association between ONJ and potent i.v. bisphosphonates. We report a case of ONJ in a patient with myeloma, who had only been treated with oral sodium clodronate. While the degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as clodronate, remains uncertain it would be prudent to consider carefully the indications for the use of these agents to minimise the risk of ONJ. [source] Fractures and avascular necrosis before and after orthotopic liver transplantation: Long-term follow-up and predictive factors,HEPATOLOGY, Issue 4 2007Maureen M. J. Guichelaar With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. Conclusion: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients. (HEPATOLOGY 2007.) [source] Vitamin D status may effect the skeletal complications of multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Terry Diamond No abstract is available for this article. [source] Crystallization of the receptor-binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragmentACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2009William J. McKinstry Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography. In this study, a monoclonal antibody Fab fragment which recognizes the same region of PTHrP as its receptor, PTH1R, was used to aid in the crystallization of PTHrP. The resultant protein complex was crystallized using the hanging-drop vapour-diffusion method with polyethylene glycol as a precipitant. The crystals belonged to the orthorhombic space group P21212, with unit-cell parameters a = 72.6, b = 96.3, c = 88.5,Å, and diffracted to 2.0,Å resolution using synchrotron radiation. The crystal structure will shed light on the nature of the key residues of PTHrP that interact with the antibody and will provide insights into how the antibody is able to discriminate between PTHrP and the related molecule parathyroid homone. [source] Preserving bone health in patients with hormone-sensitive prostate cancer: the role of bisphosphonatesBJU INTERNATIONAL, Issue 11 2009Fred Saad Men with prostate cancer initiating androgen-deprivation therapy (ADT) may have multiple factors that threaten their skeletal health, including increased fracture risk from bone loss during ADT and the propensity to develop bone metastases, which may lead to skeletal-related events (SREs). Bisphosphonates have utility in oncology for patients with bone metastases to prevent bone loss during hormonal therapy and in the benign setting to treat osteoporosis. These agents have an emerging role in patients with hormone-sensitive prostate cancer (HSPC). Etidronate, alendronate, pamidronate, and zoledronic acid have all shown efficacy in preventing ADT-related bone loss. Alendronate and zoledronic acid have also been shown to increase bone mineral density vs baseline during ADT. Patients with bone metastases from HSPC who received 4 mg zoledronic acid every 3 or 4 weeks had a low incidence of skeletal complications, although controlled study data have not been reported. Bisphosphonate treatment in men with HSPC may be effective for the prevention of ADT-related bone loss, underscoring the importance of treating early to avoid SREs and potentially delay disease progression to metastatic bone disease. [source] Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesionCANCER, Issue 1 2004Lee S. Rosen M.D. Abstract BACKGROUND Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial. METHODS Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3,4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone. RESULTS Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]). CONCLUSIONS The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36,43. © 2003 American Cancer Society. [source] Effectiveness and cost of bisphosphonate therapy in tumor bone diseaseCANCER, Issue S3 2003Jean-Jacques Body M.D., Ph.D. Abstract BACKGROUND Tumor-induced osteolysis due to breast carcinoma and myeloma is responsible for a considerable morbidity that severely impairs patients'quality of life. Osteoclast-mediated bone resorption is reported to be increased markedly in patients with tumor bone disease and can be inhibited by bisphosphonate therapy. METHODS The incidence of skeletal complications and the effectiveness of bisphosphonate therapy in patients with breast carcinoma metastatic to bone or in those with myeloma were derived from large-scale, long-term, placebo-controlled trials with clodronate or pamidronate. To the authors' knowledge, there are few studies published to date evaluating the cost-effectiveness of bisphosphonate therapy, and the majority that do exist often are based on models and are applicable only to a particular health care system. RESULTS From the placebo groups of the above-mentioned trials, one can estimate that approximately 25,40% of the patients with breast carcinoma metastatic to bone will require radiotherapy for bone pain and approximately 17,50% will sustain incident vertebral fractures yearly. The incidence of complications is reported to be lower in myeloma patients. The prolonged administration of bisphosphonates reportedly can reduce the frequency of skeletal-related events by approximately 25,50%. Maximal efficacy appears to have been achieved with the current therapeutic schemes based on monthly intravenous infusions. Beneficial effects appear to be obtained more readily using the intravenous route rather than the oral route. The costs of bisphosphonate therapy appear to be higher than the cost savings from the prevention of skeletal-related events. The costs per quality of life-adjusted year have been estimated to be > $100,000, but more research is needed. Limited data suggest that zoledronic acid will not reduce treatment costs but the short infusion time will lead to substantial time savings for patients and for outpatient oncology facilities. CONCLUSIONS As is the case for many agents used in oncology, bisphosphonates remain a relatively expensive therapy. More studies are needed to evaluate their cost-effectiveness ratio correctly. A ceiling effect has been reached with current therapeutic schemes and tailoring therapy to the individual patient needs to be evaluated correctly to increase therapeutic effectiveness and improve quality of life further without increasing treatment costs. Cancer 2003;97(3 Suppl):859,65. © 2003 American Cancer Society. DOI 10.1002/cncr.11139 [source] | ||||||||||||||||||||||