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The role of bone-modifying agents in myeloma bone disease.

Bone disease is common in patients with multiple myeloma (MM), which manifests as bone pain and skeletal-related events (SREs) such as pathological fractures and spinal cord compression. Myeloma bone disease (MBD) can adversely affect the quality of life of patients and have negative effects on morbidity and mortality. The pathogenesis of MBD is complex, and several factors are involved in the dysregulation of bone metabolism and uncoupling of bone remodeling, which result in net bone loss and devastating SREs. Broadly speaking, elevated osteoclast activity, suppressed osteoblast activity, and

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… Morgan et al. ( 54 , 55 ) (2010, 2011) | 3 | Newly diagnosed MM | Zoledronic acid IV 4 mg every 3–4 weeks ( n = 981) versus clodronic acid oral 1600 mg daily ( n = 979) until disease progression. | Skeletal related events: 27% (zoledronic acid) versus 35% (clodronic acid), p = 0.0004. … Median OS: 50.0 months (zoledronic acid) versus 44.5 months (clodronic acid), p = 0.04. …

Prevention Of Skeletal Related Events In Multiple Myeloma: Focus On The RANK-L Pathway In The Treatment Of Multiple Myeloma.

More than 90% of patients with multiple myeloma (MM) have osteolytic bone lesions which increase the risk of skeletal-related events (SRE). The cytokine milieu in the bone marrow microenvironment (BMME) of MM plays a key role in myeloma bone disease by impairing the balance between osteoclastogenesis and osteoblastogenesis. This is orchestrated by the malignant plasma cell (MPC) with the ultimate outcome of MPC proliferation and survival at the expense of excess osteoclast activation resulting in osteolytic bone lesions. Prevention of SRE is currently accomplished by the inhibition of osteocla

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… acid (CA) daily amongst 1970 patients found that ZA reduced mortality by 16% compared to CA (p=0.0118). … 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 21131037 PMC3639680 23. Wong MH , Stockler MR , Pavlakis N . …

Bone-Targeted Agents for the Management of Breast Cancer Patients with Bone Metastases.

Despite advances in adjuvant therapy for breast cancer, bone remains the most common site of recurrence. The goal of therapy for these patients is palliative and focused on maximizing the duration and quality of their life, while concurrently minimizing any disease or treatment-related complications. Bone metastases predispose patients to reduced survival, pain, impaired quality of life and the development of skeletal-related events. With an increased understanding of the pathophysiology of bone metastasis, effective treatments for their management have evolved and are now in widespread clinic

Bone-modifying therapy in multiple myeloma: a comprehensive review.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the

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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) 12:743–52. doi: 10.1016/S1470-2045(11)70157-7. PMID: 52. …

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

SLAMF7 regulates goblet cell mucus production and negatively impacts gut homeostasis and commensalism.

Crosstalk between the intestinal mucosal barrier and the gut microbiota contributes to maintaining intestinal homeostasis. Accumulating evidence suggests that diverse mechanisms are involved in maintaining intestinal homeostasis. Any disturbance in these pathways can compromise gut homeostasis and trigger chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, how host factors regulate the intestinal mucosal barrier and change the gut microbiome has not been well defined. Here, we discovered that disruption of SLAMF7 protects against intestinal inflammation. SLAMF7 def

Review of Myeloma Therapies and Their Potential for Oral and Maxillofacial Side Effects.

Myeloma is a common haematological malignancy in which adverse skeletal related events are frequently seen. Over recent years, treatment for myeloma has evolved leading to improved survival. Antiresorptive therapy is an important adjunct therapy to reduce the risk of bone fractures and to improve the quality of life for myeloma patients; however, this has the potential for unwanted side effects in the oral cavity and maxillofacial region. Osteonecrosis of the jaw related to antiresorptive medications and other myeloma therapies is not uncommon. This review serves to highlight the risk of osteo

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… 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. 6. …

Osteonecrosis of the Jaws (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma: Decreasing ONJ Incidence after Adoption of Preventive Measures.

Bisphosphonates (BPs) are administered to Multiple Myeloma (MM) patients with bone lytic lesion. Osteonecrosis of the Jaw (ONJ) is a complication reported since 2003 in patients treated with intravenous (IV) BPs such as zoledronic acid and pamidronate, with 6%-26.3% frequency in early literature series, before some preventive measures were recommended. We evaluated the occurrence of ONJ with and without dental preventive measures in MM patients treated with BPs in our centre between 1996 and 2015. Since 2005, MM patients (already under treatment or before treatment) underwent a baseline mouth

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… acid) | 1 | 0 | 0 Median N° of i.v. administrations | 14 (range 2–9) | 2.5 (range 1–16) | 11 (range 2–23) Third line bisphosphonate | Pamidronate | 3 | 5 | 1 Zoledronic acid | 2 | 0 | 0 Median N° of i.v. administrations | 6 (range 1–24) | 3 (range 1–21) | 3 (range 1–24) Total Median of i.v. administrations … 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. 35. …

Current options for the treatment of Paget's disease of the bone.

Paget's disease of bone (PDB) is a chronic bone remodelling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an i

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… With tiludronate the likelihood of a mineralization problem was largely eliminated. 33 Clodronate (clodronic acid, dichloromethylene bisphosphonate) is a bisphosphonate which has demonstrated efficacy in patients with a variety of diseases of enhanced bone resorption including PDB, hypercalcemia of …

Myeloma Bone Disease: A Comprehensive Review.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells in the bone marrow microenvironment, characterized by overproduction of heavy- and light-chain monoclonal proteins (M-protein). These proteins are mainly found in the serum and/or urine. Reduction in normal gammaglobulins (immunoparesis) leads to an increased risk of infection. The primary site of origin is the bone marrow for nearly all patients affected by MM with disseminated marrow involvement in most cases. MM is known to involve bones and result in myeloma bone disease. Osteolytic lesions are seen in 80% of patien

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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 10.1016/S1470-2045(11)70157-7 21771568 PMC3148431 130. Morgan G.J. … 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 10.1016/S0140-6736(10)62051-X 21131037 PMC3639680 131. Anderson K. Ismaila N. Flynn P.J. Halabi S. Jagannath S. Ogaily M.S. …

Practical consensus recommendaton for adjuvant bone-modifying agents in breast cancer.

Bone-modifying therapy is a primary research interest in breast cancer. Several features contribute to the importance of the bone environment in the management of breast cancer. Firstly, bone metastases represent the most common site of breast cancer metastases and secondly, the emergence of cancer treatment-induced bone loss (CTIBL) among breast cancer survivors and patients is of increasing concern. In the adjuvant setting, bisphosphonates can be given to prevent and treat tumor therapy-induced bone loss in premenopausal and postmenopausal women and, owing to their beneficial effect on bone

Zoledronic acid in the management of metastatic bone disease.

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications

Management of Myeloma Bone Lesions.

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma-cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These conseq

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… 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 10.1016/S0140-6736(10)62051-X 21131037 PMC3639680 59. Himelstein A.L. Foster J.C. Khatcheressian J.L. Roberts J.D. Seisler D.K. …

Pain Management in Patients with Multiple Myeloma: An Update.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblasti

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… The Medical Research Council (MRC) Myeloma IX trial reported a significant improvement in pain, fatigue, QoL, and physical functioning in MM patients treated with combined therapy with BPs (clodronic acid or zoledronic acid) and induction treatment [ 31 ]. … 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. 24. …

Potential role of the comprehensive tooth extraction procedure in preventing medication related osteonecrosis of the jaw (MRONJ): a prospective cohort study.

BACKGROUND: This article aims to elucidate the potential role of a comprehensive tooth extraction procedure in preventing mdication-related osteonecrosis of the jaw (MRONJ) through a prospective cohort study. By systematically assessing clinical outcomes following this procedure, the study seeks to provide evidence regarding its effectiveness in MRONJ prevention, thereby contributing to improved clinical guidelines and patient care related to dental extractions in at-risk populations. METHODS: Patients using anti-resorptive agents (ARAs) who required extraction of at least one tooth were incl

Pathophysiology and therapeutic advances in myeloma bone disease.

Bone disease is the most common complication in patients with multiple myeloma (MM), and it may lead to skeletal-related events (SREs) such as bone pain, pathological fractures, and spinal cord compression, which impair a patients' quality of life and survival. The pathogenesis of myeloma bone disease (MBD) involves disruption of bone reconstitution balance including excessive activation of osteoclasts, inhibition of osteoblasts, and participation of osteocytes and bone marrow stromal cells. Various factors, such as the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OP

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… 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. 10.1016/S0140-6736(10)62051-X 51. Rosen LS, Gordon D, Kaminski M, et al. …

Patient-reported outcome instruments used to assess pain and functioning in studies of bisphosphonate treatment for bone metastases.

PurposeWhen treating metastatic bone disease, relief of bone pain is often a key outcome. Because pain cannot be quantified with objective clinical measures, patient-reported outcome (PRO) measures are required to assess patients' subjective experience. The goal of the current review was to examine measures used to assess pain, as well as the impact of pain on functional status and health-related quality of life (HRQL), in trials of bisphosphonates for the treatment of bone metastases.MethodsA literature search focused on articles published from January 1999 to April 2009.ResultsA total of 49

Management of bone metastasis and cancer treatment-induced bone loss during the COVID-19 pandemic: An international perspective and recommendations.

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management.

Bone-targeted agents in multiple myeloma.

Osteolytic bone disease, characterized by bone pain, increased risk of pathologic fractures, tumor-induced hypercalcemia known as skeletal-related events (SREs), is a frequent complication of patients with multiple myeloma (MM) and persists even in the absence of active disease, resulting in a major cause of morbidity and mortality. The interaction between myeloma cells and their surrounding cells in the bone marrow (BM) microenvironment promotes both myeloma cell growth and bone destruction and forms the vicious cycle of MM bone disease. Therefore, therapeutic strategies targeting the interac

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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 randomized controlled trial. Lancet Oncol 2011;12:743-52. 31. Anderson KC, Alsina M, Atanackovic D, et al. …

Прогресс в оказании поддержки в проведении обзора по множественным болезням, связанным с миеломой.

Множественная миелома (ММ) — неизлечимая порча плазменных клеток, характеризующаяся увеличением производства моноклонального иммуноглобулина. Пациенты с ММ подвержены высокому риску возникновения осложнений, связанных с заболеваниями. Остеолитическая болезнь костей one - из наиболее распространенных осложнений, связанных с заболеваниями, которые приводят к хронической боли и патологии скелета, что в значительной степени способствует высоким уровням заболеваемости и смертности среди пациентов с ОМ. Помимо стандартной антиММ-терапии, для улучшения качества жизни пациентов, страдающих ММ, необход

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… Zoledronate and pamidronate should only be administered when creatinine clearance exceeds 30 mL/min, while clodronic acid should only be used when creatinine clearance exceeds 12 mL/min. … 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. 33. …