Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biophosphonates are analogues of pyrophosphate. The mechanism of action of bisphosphates is the inhibition of osteoclast activation (antiresorptive mechanism). The oral bioavailability of biophosphonates is only about 1-2%, and because of gastrointestinal side effects (mainly esophageal irritation), oral agents are less useful in oncology. Biophosphonates are used for the treatment of Paget s disease of bone, the prevention of osteoporosis, and in another clinical scenarios as the prevention of bone disease after organ transplantation. In clinical oncology biophosphonates are used for the treatment of hypercalcemia of malignancy, prevention and treatment of bone events related to bone metastases, and in the prevention of osteoporosis related to breast cancer. According to American Society of Clinical Oncology (ACO) guidelines, biophosphonates should be used in hypercalcemia of malignancy and bone events related to metastases of breast cancer and multiple myeloma.
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PMID:[Biphosphonates in oncology]. 1645 91

Multiple myeloma is the malignant proliferation of plasma cells involving more than 10% of the bone marrow. The bone complications associated with multiple myeloma include bone pain, pathologic fractures, hypercalcemia of malignancy and cord compressions. The principal pathophysiology of bone disease in multiple myeloma is a shift in the balance of bone remodeling toward bone resorption. In recent years, bisphosphonates have become an important treatment for the bone complications of multiple myeloma. Potent inhibitors of osteoclast activity, bisphosphonates interfere with biochemical pathways and induce osteoclast apoptosis. Bisphosphonates also antagonize osteoclastogenesis and promote differentiation of osteoblasts, as well as inhibiting other aspects of osteoclast homeostasis and metabolism. Several studies have evaluated treatment with bisphosphonates in patients with multiple myeloma, and have demonstrated the efficacy of clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ; www.bonefos.com), pamidronate (Aredia; Novartis Pharmaceuticals Corp; East Hanover, NJ; www.pamidronate.com) and zoledronic acid (Zometa; Novartis Pharmaceuticals Corp; East Hanover, NJ; www.us.zometa.com) in reduction of pain, reduction of SREs and survival. Moreover, recent data suggest direct and indirect antimyeloma activity of pamidronate and zoledronic acid.
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PMID:Bone complications in multiple myeloma. 1696 19

In recent years, a growing number of reports in the literature have linked osteonecrosis of the jaw bones with intravenously administered bisphosphonates prescribed for the treatment of hypercalcemia of malignancy due to bone lesions of multiple myeloma or bone metastases in patients with breast or prostate cancer. Furthermore, an association between chronic oral bisphosphonate use in patients with osteoporosis or Paget's disease, and bone necrosis in the mandible or maxilla has been demonstrated in numerous case reports and case series in the last couple of years. Therapeutically, osteonecrosis of the jaws seems to be difficult to treat surgically, often resulting in a recurring or even progressing lesion. In the present case report of a bisphosphonate-associated osteonecrosis of the maxilla in a patient with osteoporosis, the current literature will be discussed, and open research questions and potential problems for our daily dental practice routine will be addressed.
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PMID:[Biphosphonate-associated osteonecrosis of the maxilla. Case report and review of the literature]. 1707 15

Bisphosphonates as a group of drugs were introduced for the management of various conditions such as osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy, breast cancer, prostate cancer, and other tumors. This group of drugs has improved the quality of life in many patients with proven efficacy in limiting pain and skeletal-related events. The controversy of osteonecrosis of the jaws and bisphosphonates is a recent and growing problem. Osteonecrosis of the jaws is recognized as a serious complication of bisphosphonate therapy, more commonly with the intravenous form of the drugs. However, there is limited scientific understanding about the association between osteonecrosis of the jaws and bisphosphonates. In the present article we discuss various mechanisms of action of bisphosphonates, the rationale for occurrence of osteonecrosis in the jaws, and treatment guidelines for the condition.
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PMID:Bisphosphonates and osteonecrosis of the jaws: science and rationale. 1744 9

Zoledronic acid has been marketed for the past 5 years for the treatment of hypercalcemia of malignancy and malignant bone disease in patients with multiple myeloma or a broad range of solid tumors. The safety profile of zoledronic acid in this patient population is well established from the databases of several large, randomized, Phase III trials and postmarketing clinical experience. Zoledronic acid is well tolerated, with predictable side effects, primarily transient flu-like symptoms, which are manageable with standard treatment. Renal monitoring is recommended, with dose reductions for patients with renal dysfunction. Monitoring for electrolyte imbalance is also important as is calcium and vitamin D supplementation. Ocular complications are rare, and osteonecrosis of the jaw is uncommon and might be avoidable with appropriate dental care.
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PMID:The safety of zoledronic acid. 1748 Jan 79

Bisphosphonates are a class of compounds approved for the treatment of multiple myeloma, hypercalcemia of malignancy, osteolytic lesions of metastatic disease, Paget's disease, and most commonly, osteoporosis. Recently, these drugs have been associated with a new clinical entity, bisphosphonate related osteonecrosis (BRON) which is characterized by jaw necrosis that typically presents following dentoalveolar surgery. The pathogenesis for this complication appears to related to bisphosphonate mediated inhibition of osteoclast function and normal bone remodeling. This complication can have a significant impact on the quality of life for those patients with advanced stages of necrosis.
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PMID:Osteonecrosis and bisphosphonates in oral and maxillofacial surgery. 1808 78

Bisphosphonates are primary agents in the current pharmacological arsenal against osteoclast-mediated bone loss due to osteoporosis, Paget disease of bone, malignancies metastatic to bone, multiple myeloma, and hypercalcemia of malignancy. In addition to currently approved uses, bisphosphonates are commonly prescribed for prevention and treatment of a variety of other skeletal conditions, such as low bone density and osteogenesis imperfecta. However, the recent recognition that bisphosphonate use is associated with pathologic conditions including osteonecrosis of the jaw has sharpened the level of scrutiny of the current widespread use of bisphosphonate therapy. Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use.
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PMID:Bisphosphonates: mechanism of action and role in clinical practice. 1877 4

Bisphosphonates (BP) have clinically been used as a highly effective drug in the treatment of hypercalcemia of malignancy, multiple myeloma, skeletal events associated with metastatic breast cancer and prostate cancer, and osteoporosis. Despite these benefits, however, the emergence of BP-related osteonecrosis of the jaws (BRONJ) becomes a growing and significant problem in a subset of patients receiving these drugs, especially intravenous preparations. It has also been reported in the patients receiving oral BP, although the incidence is extremely low. Most of BRONJ cases occur after dental treatments such as tooth extraction, periodontal surgery, and dental implants, and are refractory to conventional treatment modalities such as debridement, antibiotics and hyperbaric oxygen therapy. As compared to EU and USA, the number of BRONJ case is still small in Japan, but it is exactly increasing year by year. The ratio of the number of BRONJ in patients receiving oral BP to that in patients receiving intravenous BP is higher in Japan than in EU and USA, speculating due to the difference of time of approval. In this communication, the practical guidelines for prevention, diagnosis and treatment of BRONJ recently released from USA and Canada were introduced. Although no effective therapy for BRONJ is established yet, the importance of oral hygiene, patient education and treatments suitable for clinical stage is emphasized. In addition, it is considered that the survey of incidence of BRONJ in Japan and the preparation of Japanese guideline are urgent need.
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PMID:[New development in bisphosphonate treatment. Bisphosphonate therapy and osteonecrosis of the jaws]. 1912 70

Bisphosphonates are currently used in the treatment of osteoporosis (postmenopausal and steroid-induced), hypercalcemia of malignancy, Paget's disease of bone, multiple myeloma, and skeletally related events associated with metastatic bone disease in breast, prostate, lung, and other cancers. There are, however, numerous other conditions where a decrease in bone remodeling by bisphosphonates might aid in disease management. The focus of this review will be to discuss a select group of conditions for which bisphosphonate therapy may be efficacious. In this review we present several cases where bisphosphonates have been used as a primary or adjunctive treatment for giant cell lesions of the jaws. Use of bisphosphonate therapy for giant cell tumors of the appendicular skeleton, pediatric osteogenesis imperfecta, fibrous dysplasia, Gaucher's disease, and osteomyelitis will be discussed. Finally, we will review previous in vivo studies on the use of bisphosphonates to augment integration and to treat osteolysis surrounding failing orthopedic implants.
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PMID:Alternative indications for bisphosphonate therapy. 1937 12

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.
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PMID:The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors. 1987 35


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