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Bone metastases in breast cancer: higher prevalence of osteosclerotic lesions.

PURPOSE: It is well known that bone metastases from breast cancer usually show osteolytic changes. We retrospectively analysed the computed tomography (CT) appearance of bone metastases to quantify the distribution of lytic, mixed and sclerotic changes in a series of patients presenting with neoplastic bone involvement from breast cancer. MATERIALS AND METHODS: Between 1996 and 2005, 468 women with a diagnosis of breast cancer were referred to our department for staging or follow-up CT examinations. Staging CT examinations detected systemic metastases in 142/468 patients, 60 of which had bone

Zoledronic acid treatment at home: safety data from an observational prospective trial.

BACKGROUND: To prospectively assess feasibility, side effects, and safety of a home treatment with zoledronic acid in patients with bone metastases confined to home. PATIENTS AND METHODS: Forty-two patients with bone metastases (15 males and 27 females; mean age, 72 years; range, 48-86), confined to home because of functional impairment or low performance status, were enrolled into the trial. They were included in a comprehensive program of home care, and were treated with zoledronic acid, 4 mg. Primary end point of this observational trial was the safety assessment of the treatment at home;

Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement.

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget's disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, alpha-alpha CTX, and beta-beta CTX) were measured at baseline and 6 months after therapy. The extent of the disease was eva

Interventions to prevent loss of bone mineral density in women receiving chemotherapy for breast cancer.

Loss of bone mineral density (BMD) is a significant problem for women receiving breast cancer treatment. The purpose of this article is to present the state of the knowledge on BMD loss and analyze interventions to prevent BMD loss in women receiving breast cancer treatment. The data sources include primary research reports, review articles, and book chapters. With increased numbers of breast cancer survivors, BMD loss experienced with treatment is a significanthealth concern because of risks of osteoporosis and bone fractures. These long-term treatment effects may significantly impact patient

Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.

PURPOSE: Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases. PATIENTS AND METHODS: ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis. RESULTS: Seventeen patients (6.7%) developed ONJ: 11 of 111 (9

An intra-patient dose-escalation study of disodium pamidronate plus radiotherapy versus radiotherapy alone for the treatment of osteolytic metastases. Monitoring of recalcification using image-processing techniques.

OBJECTIVE: To evaluate the clinical benefit and mainly to monitor quantitatively the recalcification of osteolytic lesions after radiotherapy with or without intravenous infusion of disodium pamidronate (DP) in different doses. PATIENTS AND METHODS: 42 patients with solitary lytic metastasis in weight-bearing bones were studied. Primary endpoints were the mean value and energy of gray-level histogram in plain radiographs (MVGLH and EGLH) and relative electron density (RED) of CT scans in bone lesions. In eleven patients (group A) the DP dose was increased stepwise from 90 up to 180 mg (flat d

Osteoporosis: a review and its dental implications.

Osteoporosis is a disease that affects primarily women, but can also occur in men. It is characterized by a loss of bone mineral density (BMD), and often culminates in a fracture of the hip, wrist, and/or vertebrae. The diagnosis of osteoporosis is often made by using bone density measurements. They are often expressed in relative terms (T-scores and Z-scores); the Z-score is the number of standard deviations from the age-matched average value of healthy women. A low Z-score indicates the bone density is lower than it should be for a patient's age and sex. Osteoporosis is defined as a BMD loss

Testicular germ cell tumor with rhabdomyosarcoma successfully treated by disease-adapted chemotherapy including high-dose chemotherapy: case report and review of the literature.

Treatment and prognosis have not been well characterized in germ cell tumors (GCT) with a malignant nongerm cell component. Patients with a mediastinal tumor, neural or rhabdomyosarcomatous differentiation and distant metastases have the poorest prognosis. We report a rare case of mixed GCT composed of seminoma, teratoma and rhabdomyosarcoma with the rhabdomyosarcomatous component metastasized into the liver and bone marrow (BM) causing hypercalcemia. The patient was treated with differentiation-tailored chemotherapy (CHT) including a disease-adapted high-dose (HD) CHT regimen with purified au

Bisphosphonates in the adjuvant treatment of cancer: experimental evidence and first clinical results. International Bone and Cancer Study Group (IBCG).

Several animal models, as well as a number of cell culture experiments, indicate a prophylactic effect of bisphosphonates in respect of subsequent bone metastasis. Moreover, in preliminary clinical trials involving patients with advanced breast cancer and local or remote metastases, biophosphonates produced a reduction in new skeletal metastases. This overview summarizes and discusses the results of the latest investigations. It opens with a section on the pathophysiology of bone metastasis, which is followed by a report on animal models and first studies of bisphosphonate treatment as a new a

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… Long-term controlled trial with diphosphonate in patients with osteolytic bone metastases. Lancet. 1983 Jan 22;1(8317):146–149. doi: 10.1016/s0140-6736(83)92755-1. Eventov I., Frisch B., Cohen Z., Hammel I. … Inhibition by diphosphonates of bone resorption induced by the Walker tumor of the rat. Cancer Res. 1984 Jul;44(7):3007–3011. Kanis J. A. Bone and cancer: pathophysiology and treatment of metastases. Bone. 1995 Aug;17(2 Suppl):101S–105S. doi: 10.1016/8756-3282(95)00194-i. Kanis J. …

Cardiac Amyloidosis and its New Clinical Phenotype: Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is now an emerging cardiovascular epidemic, being identified as the main phenotype observed in clinical practice. It is more associated with female gender, advanced age and comorbidities such as hypertension, diabetes, obesity and chronic kidney disease. Amyloidosis is a clinical disorder characterized by the deposition of aggregates of insoluble fibrils originating from proteins that exhibit anomalous folding. Recently, pictures of senile amyloidosis have been described in patients with HFpEF, demonstrating the need for clinical cardiolog

Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases.

Purpose(153)Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated.MethodsPatients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg (153)Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with

Histopathological findings affect quantitative values of single photon emission computed tomography in patients with antiresorptive agent-related osteonecrosis of the jaws.

OBJECTIVES: This study investigated the relationships between quantitative values calculated from bone single photon emission computed tomography/computed tomography (SPECT/CT) images and histopathological findings observed in surgical specimens from patients with antiresorptive agent-related osteonecrosis of the jaw (ARONJ); it sought to clarify histopathological factors that cause accumulation in bone SPECT/CT images of patients with ARONJ. METHODS: This study included 81 pathological specimens of 21 lesions obtained from 18 patients with ARONJ who underwent SPECT/CT and jaw resection. The

Zoledronate promotes bone formation by blocking osteocyte-osteoblast communication during bone defect healing.

Nitrogen-containing bisphosphonates (N-BPs) are potent antiresorptive drugs and their actions on osteoclasts have been studied extensively. Recent studies have suggested that N-BPs also target bone-forming cells. However, the precise mechanism of N-BPs in osteoblasts is paradoxical, and the specific role of osteocytes is worthy of in-depth study. Here, we investigated the cellular mechanisms of N-BPs regulating bone defect healing by zoledronate (ZA). Bone histomorphometry confirmed an increase in new bone formation by systemic ZA administration. ZA induced more alkaline phosphatase-positive o

Children with severe Osteogenesis imperfecta and short stature present on average with normal IGF-I and IGFBP-3 levels.

BACKGROUND: Osteogenesis imperfecta (OI) is characterized by bone fragility and short stature. Data about IGF-I/IGFBP-3 levels are rare in OI. Therefore IGF-I/IGFBP-3 levels in children with different types of OI were investigated. METHODS: IGF-I and IGFBP-3 levels of 60 children (male n=38) were assessed in a retrospective cross-sectional setting. RESULTS: Height/weight was significant different [height z-score type 3 versus type 4: p=0.0011 and weight (p≤0.0001)] between OI type 3 and 4. Mean IGF-I levels were in the lower normal range (mean±SD level 137.4±109.1 μg/L). Mean IGFBP-3 measure

Incidence of bisphosphonate-related osteonecrosis of the jaw in high-risk patients undergoing surgical tooth extraction.

As the most suitable approach for preventing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing surgical tooth extraction is still under discussion, the present study evaluates the incidence of BRONJ after surgical tooth extraction using a standardized surgical protocol in combination with an adjuvant perioperative treatment setting in patients who are at high-risk for developing BRONJ. High-risk patients were defined as patients who received intravenous bisphosphonate (BP) due to a malignant disease. All teeth were removed using a standardized surgical protocol. Th

Surgical Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw: Six-Year Experience of a Single Institution.

PURPOSE: Bisphosphonates are drugs commonly used to treat osteoporosis, hypercalcemia of malignancy, and bone metastases. In some cases, its administration has been associated with osteonecrosis of the jaws. The management of medication-related osteonecrosis of the jaw (MRONJ) has not been completely elucidated, and its treatment can vary from no or limited surgery to more extensive surgery. The objective of the present study was to evaluate the efficacy of surgical therapy for patients presenting with MRONJ. PATIENTS AND METHODS: A retrospective study was conducted that evaluated all MRONJ c

Prelamin A accumulation in endothelial cells induces premature senescence and functional impairment.

BACKGROUND: Defects in lamin A maturation result in premature aging syndromes and severe atherosclerosis as observed in the Hutchinson-Gilford Progeria Syndrome. In age-related atherosclerosis, several features of cellular senescence have been characterized in endothelial cells including telomere shortening and increased oxidative stress. However, to date, very little is known about lamin A alterations in these cells. OBJECTIVES: To study lamin A-related senescence and its consequences in the activation status of primary endothelial cells. METHODS: Healthy primary endothelial cells and proge

Time course of bone mineral density changes with denosumab compared with other drugs in postmenopausal osteoporosis: a dose-response-based meta-analysis.

OBJECTIVE: Our objective was to compare the time course of bone mineral density (BMD) changes at the lumbar spine (LS) and total hip (TH) in postmenopausal women during treatment with denosumab, bisphosphonates, selective estrogen receptor modulators, PTH, or calcitonin. DATA SOURCES AND STUDY SELECTION: Data were extracted from 142 randomized controlled trials for prevention or treatment of postmenopausal osteoporosis representing over 113,000 women. DATA EXTRACTION AND DATA SYNTHESIS: The percent change from baseline in BMD was analyzed using a nonlinear least-squares random-effects meta-r

Oxidative stress in bisphosphonate-related osteonecrosis of the jaws.

OBJECTIVES: To analyze whether oxidative stress (OS) changes are present in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus controls. MATERIALS AND METHODS: Oxidative stress was analyzed in serum and unstimulated saliva of three groups: Group 1 consisted of 24 patients who had been treated with intravenous bisphosphonates (ivBPs) and developed BRONJ, group 2 consisted of 20 patients who had received ivBPs and did not develop BRONJ, and group 3 comprised 17 control subjects. Reduced glutathione (GSH), malondialdehyde (MDA), oxidized glutathione (GSSG), and 8-oxo-7,

Home-based zoledronic acid infusion therapy in patients with solid tumours: compliance and patient-nurse satisfaction.

PURPOSE: This study aimed to explore patient and nurse satisfaction, compliance with best practice, technical feasibility and safety of home infusion of the bisphosphonate zoledronic acid (ZOL). METHODS: This was a prospective 1-year survey of home ZOL therapy (4 mg Zometa, 15-min i.v., every 3-4 weeks) in patients with bone metastases secondary to a solid malignancy. A physician questionnaire, nurse satisfaction/feasibility questionnaire and patient satisfaction questionnaire were administered at several time-points. RESULTS: Physician participation rate was 56.5% (87/154). Physicians enrol