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Guidelines on the diagnosis and management of multiple myeloma treatment: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Project guidelines: Associação Médica Brasileira - 2012.

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A clinical prediction model for outcome and therapy delivery in transplant-ineligible patients with myeloma (UK Myeloma Research Alliance Risk Profile): a development and validation study.

BACKGROUND: Tolerability of treatments for multiple myeloma can depend on the characteristics of the patient being treated. We aimed to develop and validate a risk profile, using routinely collected data, that could predict overall survival in patients with multiple myeloma who were ineligible for stem-cell transplantation. METHODS: We used patient data from two randomised controlled trials done in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation (the NCRI Myeloma XI study [NCRI-XI, n=1852] and the MRC Myeloma IX study [MRC-IX, n=520]), to devel

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… Patients were also assigned to bisphosphonate treatment (oral clodronic acid 1600 mg per day or intravenous zoledronic acid 4 mg every 21–28 days with induction chemotherapy, and every 28 days thereafter). … acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial Lancet 376 2010 1989 1999 21131037 10.1016/S0140-6736(10)62051-X PMC3639680 16 Morgan GJ Gregory WM Davies FE The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis Blood 119 …

Risk of Early Mortality in Patients With Newly Diagnosed Multiple Myeloma.

The overall survival of patients with multiple myeloma (MM) has been improved greatly over the last 2 decades with the broader use of novel drugs and autologous tandem transplantation. However, more than one tenth of myeloma patients still die shortly after diagnosis. We therefore aim to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with MM. We included in this study 451 consecutive patients with MM, newly diagnosed at an Asian tertiary medical center between January 1, 2002 and April 30, 2015. A total of 57 subjects who experienced early mo

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… Some studies have shown that subsets of myeloma patients receiving bisphosphonates saw improved overall survival. 33 – 35 Furthermore, Morgan et al 36 reported that zoledronic acid reduced mortality by 16% compared to that of clodronic acid. … First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet (Lond, Engl) 2010; 376:1989–1999. 37. Ramsingh G, Mehan P, Luo J, et al. …

Diagnosis and treatment of bone disease in multiple myeloma: spotlight on spinal involvement.

Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation

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… multiple-event analysis for the evaluation of treatment effects of zoledronic acid in patients with bone metastases from solid tumors Supportive Cancer Therapy 2005 2 4 234 240 18628179 10.3816/SCT.2005.n.017 78 Morgan GJ Davies FE Gregory WM First-line treatment with zoledronic acid as compared with clodronic … acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial The Lancet 2010 376 9757 1989 1999 2-s2.0-78650174738 10.1016/S0140-6736(10)62051-X PMC3639680 21131037 79 Morgan GJ Child JA Gregory WM Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly …

Caspase-Dependent HMGB1 Release from Macrophages Participates in Peripheral Neuropathy Caused by Bortezomib, a Proteasome-Inhibiting Chemotherapeutic Agent, in Mice.

Given the role of macrophage-derived high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel, we analyzed the role of HMGB1 and macrophages in the CIPN caused by bortezomib, a proteasome-inhibiting chemotherapeutic agent used for the treatment of multiple myeloma. Repeated administration of bortezomib caused CIPN accompanied by early-stage macrophage accumulation in the dorsal root ganglion. This CIPN was prevented by an anti-HMGB1-neutralizing antibody, thrombomodulin alfa capable of accelerating thrombin-dependent degradation of HMGB1, anta

Clinical role of bisphosphonate therapy.

Bisphosphonates (BPs) are synthetic analogues of pyrophosphate. They inhibit bone resorption and are therefore widely used in disorders where there are increases or disruptions in bone resorption. This includes postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, Paget's disease of bone, and malignancy-related bone loss. To best understand the clinical application of BPs, an understanding of their pharmacokinetics and pharmacodynamics is important. This review describes the structure, pharmacology and mode of action of BPs, focusing on their role in clinical practice. Controversie

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… Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12(8):743–752. doi: 10.1016/S1470-2045(11)70157-7. 69. …

Safety Profile and Predictors of Adverse Events of Incadronate Disodium in Treating Breast Cancer Patients with Bone Metastases: A Retrospective Study.

PURPOSE: Bone metastasis is a common complication in advanced breast cancer. Bisphosphonates like incadronate disodium have shown potential in reducing bone resorption and skeletal-related events. We therefore performed a retrospective study to evaluate the safety profile of incadronate disodium in breast cancer patients with bone metastases. PATIENTS AND METHODS: This retrospective study was conducted involving 84 breast cancer patients with bone metastases who received incadronate disodium treatment between February 2022 and August 2024 in our center. The primary endpoint was the incidence

Osteoarthritis of the knee - biochemical aspect of applied therapies: a review.

The most prevalent form of arthritis is osteoarthritis (OA) of the knee, which is characterized by a degeneration of articular cartilage resulting in the development of osteophytes, or bone spurs. Main goals of OA treatment are to reduce pain, slow the disease progression, and improve joint function and the quality of life. The purpose of this study was to verify all the therapies recommended by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) from the biochemical point of view. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesi

The role of the bone microenvironment in regulating myeloma residual disease and treatment.

Multiple myeloma is an incurable haematological cancer. The increase in targeted therapies has improved the number of myeloma patients achieving a complete response and improved progression-free survival following therapy. However, a low level of disease or minimal residual disease (MRD) still persists which contributes to the inevitable relapse in myeloma patients. MRD has been attributed to the presence of dormant myeloma cells and their subsequent reactivation, which is controlled by the microenvironment and specialised niches within the bone marrow. This contributes to the evasion of the i

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… Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (Mrc myeloma ix): Secondary outcomes from a randomised controlled trial. Lancet Oncol (2011) 12(8):743–52. doi: 10.1016/s1470-2045(11)70157-7 49. …

Efficacy and Safety of Zoledronic Acid and Pamidronate Disodium in the Treatment of Malignant Skeletal Metastasis: A Meta-Analysis.

Solid tumors frequently metastasize to bone. Two bisphosphonates have been investigated for bone metastases including pamidronate disodium and zoledronic acid.By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, we conducted a meta-analysis to determine the efficacy and safety of zoledronic acid compared with pamidronate disodium in reducing pain in patients with bone metastases.Studies were pooled, and the relative risk (RR) and its corresponding 95 % confidence interval (CI) were calculated. Version 12.0 STATA software was used for statistic

Importance of Whole-Body Scintigraphy or Positron Emission Tomography for Early Detection of Femoral Lesions in Breast Cancer Patients Treated with Bisphosphonates.

BackgroundWe hypothesized that most of the atypical femoral fractures (AFFs) associated with bisphosphonate treatment for breast cancer (BC) could be found before the fracture event in another radiological examination already performed by breast surgeons, rather than on simple radiographs (SRs).MethodsWe thoroughly inspected the clinical charts of BC patients treated at our institute between 2008 and 2017. In total, 228 patients were categorized into three groups based on SRs: complete AFF on at least one side (group 1); incomplete fracture on at least one side, but not any complete fracture (

Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.

BackgroundBone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC.Patients and methodsData on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed.ResultsMedian time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk

The emerging role of osteoclasts in the treatment of bone metastases: rationale and recent clinical evidence.

The occurrence of bone metastasis is a grave medical concern that substantially impacts the quality of life in patients with cancer. The precise mechanisms underlying bone metastasis remain unclear despite extensive research efforts, and efficacious therapeutic interventions are currently lacking. The ability of osteoclasts to degrade the bone matrix makes them a crucial factor in the development of bone metastasis. Osteoclasts are implicated in several aspects of bone metastasis, encompassing the formation of premetastatic microenvironment, suppression of the immune system, and reactivation o

Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer.

There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current underst

Initiation and interruption in intravenous bisphosphonate therapy among patients with multiple myeloma in the United States.

BackgroundPrior to 2018, intravenous bisphosphonates (IV BPs) were the only therapies recommended to prevent skeletal-related events for patients diagnosed with multiple myeloma (MM). We examined patterns of IV BP initiation and interruption among patients with newly diagnosed MM (NDMM) in the United States.MethodsElectronic health records linked to administrative health insurance claims were used to identify adults with NDMM between 1 January 2011 and 30 April 2016. Patients were excluded for recent IV BP use or concurrent cancer. The incidences of IV BP initiation and interruption were estim

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… Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12:743‐752. 6. Berenson JR, Lichtenstein A, Porter L. … First‐line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376:1989‐1999. 17. O'Donnell EK, Raje NS. Myeloma bone disease: pathogenesis and treatment. Clin Adv Hematol Oncol. 2017;15:285‐295. 18. …

A national portfolio of bone oncology trials-The Canadian experience in 2012.

BackgroundThe impact of both cancer and its treatment on bone is an essential component of oncological practice. Bone oncology not only affects patients with both early stage and metastatic disease but also covers the entire spectrum of tumour types. We therefore decided to review and summarise bone oncology-related trials that are currently being conducted in Canada.MethodWe assessed ongoing and recently completed trials in Canada. We used available North American and Canadian cancer trial websites and also contacted known investigators in this field for their input.ResultsTwenty seven clinic

Oral health status and quality of life in female patients receiving low dose bone-modifying agents for cancer treatment-induced bone loss: a single-center exploratory study.

INTRODUCTION: Breast cancer patients, undergoing low-dose bone-modifying agent (LD-BMA) therapy for cancer treatment-induced bone loss (CTIBL), represent an emerging category at risk of Medication-Related (MRONJ) low (<1%) but not absent. However, data on their oral health status and quality of life related are currently limited. This single-center exploratory study aimed to assess oral health conditions, periodontal status, and oral health-related quality of life in non-metastatic breast cancer patients under LD-BMA therapy for CTIBL. MATERIALS AND METHODS: Forty patients were consecutively

First-Line Combination with Proteasome Inhibitor-Based Treatment and Zoledronic Acid Is Effective in Reducing Later Fractures in Multiple Myeloma Irrespective of Multiple Myeloma Bone Disease at Diagnosis.

The present study provides real-world evidence on the treatment of multiple myeloma (MM) bone disease with various bisphosphonates combined for different myeloma-specific treatments as no validated data regarding the best combination treatment for bone disease associated with MM are available. We examined retrospectively 345 MM patients treated with autologous stem cell transplantation in Finland during 1996-2020. The median age of the patients was 60 years with a median follow-up time of 50 months (1-339). At diagnosis, 72.1% of the patients had myeloma-associated bone disease and 45.8% had f

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… Another study compared ZA to clodronic acid, and patients receiving ZA improved their PFS but not OS [ 14 , 15 ]. … First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): A randomised controlled trial. Lancet. 2010;376:1989–1999. doi: 10.1016/S0140-6736(10)62051-X. 15. …

New dimensional staging of bisphosphonate-related osteonecrosis of the jaw allowing a guided surgical treatment protocol: long-term follow-up of 266 lesions in neoplastic and osteoporotic patients from the university of bari.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the most serious side effect in patients receiving bisphosphonates (BPs) for neoplastic disease and osteoporosis. The aim of this study is to propose a new dimensional stage classification, guiding the surgical treatment of BRONJ patients, and to evaluate the success rate of this new management. From 2004 to 2013, 203 neoplastic and osteoporotic patients with 266 BRONJ lesions were referred to the Odontostomatology Unit of the University of Bari. All patients underwent surgery after suspension of BPs therapy and antibiotic treatment. T

Bone-Targeted Agents in Breast Cancer: Do We Now Have All the Answers?

The bone-targeted agents (BTAs), bisphosphonates and denosumab, have an established role in the treatment of metastatic breast cancer bone disease and the prevention of cancer-treatment-induced bone loss. Evidence in support of their ability to improve survival in early breast cancer now indicates that the bisphosphonates are effective in postmenopausal women (naturally or chemically induced), but denosumab does not have similar benefits when added to standard adjuvant therapy. In postmenopausal women with early breast cancer, the choice of BTA may differ depending on the indication for treatm