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Pathological Fractures (pathological + fractures)
Selected AbstractsIdentification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2INTERNATIONAL JOURNAL OF CANCER, Issue 4 2010Wen Min Lau Abstract Breast cancer metastases develop in the bone more frequently than any other site and are a common cause of morbidity in the form of bone pain, pathological fractures, nerve compression and life-threatening hypercalcemia. Despite ongoing research efforts, the molecular and cellular mechanisms that regulate breast cancer cell homing to and colonization of the bone as well as resultant pathological bone alteration remain poorly understood. To identify key mediators promoting breast cancer metastasis to bone, we utilized an immunocompetent, syngeneic murine model of breast cancer metastasis employing the mammary tumor cell line NT2.5. Following intracardiac injection of NT2.5 cells in neu-N mice, metastases developed in the bone, liver and lung, closely mimicking the anatomical distribution of metastases in patients with breast cancer. Using an in vivo selection process, we established NT2.5 sublines demonstrating an enhanced ability to colonize the bone and liver. Genome-wide cDNA microarray analysis comparing gene expression between parental NT2.5 cells and established sublines revealed both known and novel mediators of bone metastasis and osteolysis, including the transcriptional co-activator CITED2. In further studies, we found that expression of CITED2 was elevated in human primary breast tumors and bone metastasis compared to normal mammary epithelium and was highest in breast cancer cell lines that cause osteolytic bone metastasis in animal models. In addition, reducing CITED2 expression in NT2.5 cells inhibited the establishment of bone metastasis and osteolysis in vivo, suggesting a potential role for CITED2 in promoting breast cancer bone metastasis. [source] Severe Malignant Osteopetrosis Caused by a GL Gene Mutation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2004Paola Quarello Abstract Infantile malignant autosomal recessive osteopetrosis is a genetically heterogeneous disease caused by the inability of OCLs to resorb and remodel bone, resulting in generalized osteosclerosis and obliteration of marrow spaces and cranial foramina. The classical clinical features are pathological fractures, visual impairment, and bone marrow failure. Two human genes have been described as the cause of this form of osteopetrosis: the T-cell immune-regulator-1 (TCIRG1) gene, which is mutated in >50% of the patients, and the chloride channel 7 (ClCN7) gene, which accounts for ,10% of cases. We report the clinical, radiographic, and histopathologic findings of the first human osteopetrosis case caused by a mutation in the grey-lethal (GL) gene. The patient, a 9-day-old male infant, presented with a very severe osteopetrotic phenotype including substantial hepatosplenomegaly since birth, cytopenia, and progressive major liver failure. Skeletal radiographs revealed a generalized increase in bone density with loss of corticomedullary differentiation. Histopathologic bone examination showed the typical osteopetrotic changes, with absence of resorptive activity, and osteoclasts, slightly decreased in number, with evident morphological alterations. [source] Incidence of Hip and Other Osteoporotic Fractures in Elderly Men and Women: Dubbo Osteoporosis Epidemiology Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Kevin P Chang Abstract In this prospective 12-year study in men and women 60 years of age and older, there was a 4,6% per year reduction in the incidence rate of overall osteoporotic fractures, but the study was unable to exclude any change in the hip fracture incidence rate. Approximately one-half of hip fractures occurred before 80 years in men and two-thirds before 85 years in women. The age distribution of hip fractures underlines the need for earlier intervention in osteoporosis. Introduction: Although hip fracture is the major osteoporotic fracture in terms of health outcomes, quality of life, and costs, there is a paucity of long-term data on secular changes in men and women within a defined community. This long-term prospective population-based study over 12 years from 1989 to 2000 specifically examined the age distribution and secular changes in the incidence rates of hip and other osteoporotic fractures in men and women 60 years of age and older in a predominantly white population in Dubbo, Australia. Materials and Methods: Hip and all other clinical fractures were ascertained by reviewing all radiography reports from the two area radiology services, ensuring complete ascertainment of all clinical osteoporotic fractures. Results and Conclusion: Among the 1055 symptomatic atraumatic fractures (after excluding pathological fractures), there was a significant reduction in the overall fracture incidence rate in women (4% per year; p = 0.0003) and men (6% per year; p = 0.0004) over the 12 years. There were 229 hip fractures (175 in women and 54 in men) within 39,357 person-years of observation. The overall rate ± SE of hip fracture was 759 ± 57 per 100,000 person-years in women and 329 ± 45 per 100,000 person-years in men, with an exponential increase with age. With advancing age, the incidence rate of hip fractures in men approached that in women; the female:male ratio fell from 4.5 (95% CI: 1.3,15.7) to 1.5 (0.9,2.5) and 1.9 (1.2,2.8) in the 60,69, 70,79, and 80+ year age groups, respectively. In women, the absolute number of fractures and incidence rate continuously increased with age; however, in men, the absolute number of hip fractures peaked at 80,84 years of age and then decreased. Most importantly, despite the continuing increase with age, almost one-half (48%) of the hip fractures occurred before the age of 80 years in men, and 66% of hip fractures occurred before the age of 85 years in women. The overall hip fracture incidence is comparable with other white (except Sweden) and Asian groups as well as two other Australian studies. This study could not exclude a change in hip fracture incidence rate, even in those 80 years of age and over among whom the incidence of hip fractures was the highest. The incidence data highlight the fact that a large proportion of hip fractures occurs in those under 80 years of age, particularly in men. This age distribution underlines the need for earlier intervention in osteoporosis in women and particularly in men to achieve the most cost-effective outcomes. [source] Common complaints, difficult diagnosis: Multiple myelomaJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 5 2006Clinical Nurse), Colleen Dvorak RN, OCN (Graduate student, currently in the Acute Care Nurse Practitioner Program with a focus in oncology Abstract Purpose: To review the presenting signs and symptoms of multiple myeloma, its pathophysiology, diagnostic evaluation, and treatment options. Data sources: A literature review of research articles and publications by oncology experts who specialize in multiple myeloma, supplemented by a case study. Conclusions: Multiple myeloma is a cancer of the geriatric population, with the average age at diagnosis between 65 and 68 years. As the population of those over age 65 is predicted to double by the year 2050, the incidence of myeloma is expected to increase. Nurse practitioners (NPs) must become familiar with the signs, symptoms, and complications of myeloma for patients to be diagnosed and referred to specialists in a timely manner. Implications for practice: Patients with multiple myeloma often present with vague, common symptoms such as back pain, bony pain, fatigue, and anemia. These symptoms may be treated as separate medical conditions if NPs fail to include multiple myeloma in their differential diagnosis. If NPs are educated on this malignancy, they will have the expertise to look for other signs of the disease such as hypercalcemia, pathological fractures, osteopenia, or renal failure. Without early recognition of multiple myeloma and referrals to oncology specialists, patients are left with a delayed diagnosis and poor symptom control. [source] Novel intraoral phenotypes in hyperimmunoglobulin-E syndromeORAL DISEASES, Issue 1 2008DL Domingo Aim:, Hyperimmunoglobulin-E syndrome (HIES) is a primary immunodeficiency characterized by eczema, recurrent skin and lung infections with pneumatocoele formation, and extremely elevated serum immunoglobulin-E. The precise immunologic defect and genetic etiology remain unknown. Non-immunologic findings include characteristic facial features (prominent forehead, fleshy nasal tip, and increased interalar distance); skeletal involvement (pathological fractures, scoliosis, and craniosynostosis); and retention of primary teeth. This study aims to characterize intraoral soft tissue findings in HIES patients. Methods:, Sixty HIES patients (4,54 years, 27 males, 33 females) received intraoral and radiographic evaluations. Chronological dental development was also assessed. Results:, Lesions of the hard palate and dorsal tongue were found in 55% and 60% of patients, respectively. Palatal lesions ranged from a generalized surface keratosis to a midline sagittal fibrotic bridge. Tongue lesions consisted of multiple fissures and a midline cleft. On the lip and buccal mucosa, keratotic plaques and/or surface fissures were found in 8% and 23% of patients, respectively. Manifested in 76.7% of patients, the intraoral lesions were significantly more prevalent than the characteristic facial traits (P = 0.0013). Conclusions:, Alterations in oral mucosa and gingiva were present in the majority of HIES patients. These novel intraoral findings may facilitate the diagnosis of HIES. [source] INJECTABLE FORM OF CALCIUM SULPHATE AS TREATMENT OF ANEURYSMAL BONE CYSTSANZ JOURNAL OF SURGERY, Issue 5 2008Mark Clayer Background: Aneurysmal bone cysts (ABC) are a rare condition in adolescents and teenagers but may result in pain, fracture and growth abnormalities. The gold standard of open curettage carries the risk of surgical complications and still a local recurrence rate of 20,30%. Percutaneous treatment of ABC have rarely been reported and a poor response the usual outcome. This study investigated a new technique of percutaneous aspiration and injection of ABC using an aqueous solution of calcium sulphate. Methods: A radiological diagnosis of a bone cyst was made in 15 consecutive patients and pathologically confirmed as ABC. Most had already sustained a fracture and/or had been previously unsuccessfully treated by minimally invasive techniques including embolization or methylprednisolone injection. The procedure of aspiration and injection with calcium sulphate was undertaken, and the patients were reviewed regularly both clinically and radiologically for a minimum of 2 years. Results: The calcium sulphate cement was reabsorbed completely within 8 weeks. The first osseous response was periosteal new bone formation circumferentially followed by gradual opacification of the cystic cavity. All except one patient that described pain before the procedure reported complete relief of symptoms by 4 weeks. Two patients developed a local recurrence of the cyst, and one subsequently developed a pathological fracture. Two patients sustained pathological fractures through healed cysts, 12 and 22 months after the procedure, respectively. Conclusions: This new technique has shown good early clinical and radiological responses and a low complication rate in a consecutive group of patients with ABC. [source] Osteoclast-targeting small molecules for the treatment of neoplastic bone metastasesCANCER SCIENCE, Issue 11 2009Makoto Kawatani Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors. (Cancer Sci 2009) [source] Decreased bone density and treatment in patients with autosomal recessive cutis laxaACTA PAEDIATRICA, Issue 3 2009C Noordam Abstract Aim: Due to the occasional association pathological fractures and osteoporosis we evaluated four patients with cutis laxa syndrome for skeletal anomalies. Patient/Methods: We prospectively evaluated four patients, a male and a female child and a brother-sister sib pair, with dysmorphic features, growth delay, joint anomalies, psychomotor retardation and congenital cutis laxa. The clinical features and the family history were suggestive for autosomal recessive cutis laxa syndrome type II, partially overlapping with geroderma ostedysplastica. Skeletal survey, sequential bone density measurements, endocrine and metabolic investigations were performed including N- and O-linked glycosylation analysis. ATP6V0A2 and FBLN5 mutations were ruled out in all patients. Results: All children were diagnosed with significantly decreased bone density, especially in the lumbar spine, including spontaneous vertebral and rib fractures in three children. Following 24 months of bisphosphonate treatment a total restitution of bone density was observed in three cases and no relapse was detected in the 2-year follow-up period. A spontaneous improvement was found in one female during puberty. Conclusion: Bone disease might occur early in the course in autosomal recessive cutis laxa syndrome. We report on a significant clinical improvement and stabilization in our patients following bisphosphonate therapy. We suggest early, systemic evaluation and follow up of bone density in all children presenting with inherited cutis laxa. [source] | ||||||||||