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

Nitrogen-containing biphosphonates are a group of medications that are increasingly used in the management of Paget's disease, fibrous dysplasia, osteoporosis, multiple myeloma and metastatic prostate or breast cancer bone disease. On 2004 it was established that nitrogen-containing biphosphonates may induce jaw osteonecrosis and since then, a substantial number of publications has supported this finding. Jaw osteonecrosis may be asymptomatic, lasting for about a year or symptomatic, accompanied with mild or severe pain. Jaw osteonecrosis usually results in patients with poor dental hygiene, or subjected to invasive dental procedures. Its incidence increases with the length of nitrogen-containing biphosphonates treatment and appears to be higher for the Zometa(TM) users. It is important to early recognize this entity, since early intervention can make a significant difference to the outcome of this debilitating side effect. We here report three patients who had a positive technetium-99m methylene diphosphonate ((99m)Tc-MDP) bone scan. One of these patients also had osteomyelitis and was treated aggressively. The other two were treated in a more conservative manner. Detailed dental examination supported the scintigraphic findings. Biopsy was performed only in one patient and also offered specimens for antibiotic cultures. In discussion, jaw biopsy is a debatable procedure in the setting of jaw osteonecrosis and many consider that it should be avoided in most cases, except if it is necessary to establish the diagnosis and suggest antibiotic treatment by obtaining samples for bacterial cultures. Although axial tomography and magnetic resonance imaging are useful in defining the extent of the disease, 3-phase (99m)Tc-MDP bone scan is the most sensitive imaging modality pinpointing the disease at its early stages. In conclusion, a 3-phase (99m)Tc-MDP scan with anterior and lateral views of the skull is indicated in all symptomatic or asymptomatic patients, with a history of long-term nitrogen-containing biphosphonate treatment, since this may lead to an early detection of the disease.
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PMID:Jaw uptake of technetium-99 methylene diphosphonate in patients on biphosphonates: a word of caution. 1808 61

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

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.
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PMID:Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis. 1831 5

Osteoclasts are multinucleated haematopoietic cells that resorb bone. Increased osteoclast activity causes osteoporosis, a disorder resulting in a low bone mass and a high risk of fractures. Increased osteoclast size and numbers are also a hallmark of other disorders, such as Paget's disease and multiple myeloma. The protein c-Fos, a component of the AP-1 transcription factor complex, is essential for osteoclast differentiation. Here we show that the Fos-related protein Fra-2 controls osteoclast survival and size. The bones of Fra-2-deficient newborn mice have giant osteoclasts, and signalling through leukaemia inhibitory factor (LIF) and its receptor is impaired. Similarly, newborn animals lacking LIF have giant osteoclasts, and we show that LIF is a direct transcriptional target of Fra-2 and c-Jun. Moreover, bones deficient in Fra-2 and LIF are hypoxic and express increased levels of hypoxia-induced factor 1alpha (HIF1alpha) and Bcl-2. Overexpression of Bcl-2 is sufficient to induce giant osteoclasts in vivo, whereas Fra-2 and LIF affect HIF1alpha through transcriptional modulation of the HIF prolyl hydroxylase PHD2. This pathway is operative in the placenta, because specific inactivation of Fra-2 in the embryo alone does not cause hypoxia or the giant osteoclast phenotype. Thus placenta-induced hypoxia during embryogenesis leads to the formation of giant osteoclasts in young pups. These findings offer potential targets for the treatment of syndromes associated with increased osteoclastogenesis.
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PMID:Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia. 1854 6

Millions of patients in the United States take bisphosphonates for management of malignant bone metastases, osteoporosis, osteitis deformans (Paget's disease), and osteogenesis imperfecta. Since 2003, over 200 cases of osteonecrosis of the jaws have been described, mostly in patients with multiple myeloma or breast cancer patients, and to a lesser extent in patients on oral medications.
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PMID:Bisphosphonates, osteonecrosis of the jaw, and dental treatment recommendations. 1859 21

Bisphosphonates (BPs), as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition. BPs, potent inhibitors of osteoclast-mediated bone resorption, were first introduced more than 20 years ago. Since then, they have been used widely in the management of bone diseases, including hypercalcemia related to malignancy, myeloma-related bone disease, Paget's disease and osteoporosis. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These additional features have made BPs useful in the treatment of metastatic disease, including breast and prostate cancer, resulting in a rise in the medical use of these drugs. However, recent reports suggest that BPs, particularly the nitrogen-containing BPs pamidronate (Aredia) and zoledronic acid (Zometa), both manufactured by Novartis of East Hanover, NJ, are capable of causing bisphosphonate-associated osteonecrosis of the jaw (BON). With 2.5 million patients treated with pamidronate and/or zoledronate worldwide, BON occurs in about one per 10,000 treated patients (Novartis, unpublished data, 2004). Currently, the total number of reported cases associated with alendronate (Fosamax, Merck and Co. Inc., White-house Station, NJ) the most commonly prescribed oral bisphosphonate, is approximately 170 worldwide (C. Arsver, oral communication, March 2006). This corresponds to a spontaneous BON incidence of approximately 0.7 cases per 100,000-years exposure. However, there is insufficient data to determine why the osteonecrosis reported seems to particularly affect the jaw, with a slightly higher rate in the mandible than the maxilla. This report concerns the management of a patient with BON. Information provided includes: the pharmacologic properties of the several bisphosphonates currently available; the pathobiological mechanism; the clinical presentation of the oral lesions; and recommendations for the oral management of patients who have received BP therapy, with consideration of a preventative approach based on current knowledge.
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PMID:Bisphosphonate-associated osteonecrosis: a clinician's reference to patient management. 1876 52

Lately clinical evidence has suggested that the development of osteonecrosis of the jaws (ONJ) might be associated to assumption of high doses of nitrogen-bisphosphonate (N-BPs), quite common in the treatment of multiple myeloma and skeletal metastasis due to breast and prostate cancer. Bisphosphonates are used for the treatment of several pathologies such as osteoporosis, Paget's disease, multiple myeloma, malignant hypercalcemia, breast and prostate tumours, and other tumours associated with bone metastasis. Their use might improve patient's life standard, reducing pain and complications of the skeletal structure. In this report three clinical cases of ONJ of patients in treatment with BPs are presented, and the possible pathogenesis is analysed. Further-more, treatment guidelines for the management of patients in treatment with BPs who need restorative dental care and oral surgery are proposed.
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PMID:Clinical guidelines for prevention of osteonecrosis of the jaws in patients in treatment with bisphosphonates: literature review and report of three cases. 1892 78

Bisphosphonates are widely used in the treatment of nonmalignant bone disease like osteoporosis, Paget's disease and malignant disease like malignant hypercalcemia, osteolytic metastasis from breast and prostate cancer and multiple myeloma. Jaws osteonecrosis is described since 2003 and is more often associated with the intraveinous use than oral use. Higher risk of osteonecrosis is noted after 3 years of osteoporosis treatment. The precipitating event is often a tooth extraction or other invasive procedure. There is no effective treatment for this pathology. Careful oral examination is necessary before prescribing bisphosphonates and dental treatment must be achieved before the initiation of treatment.
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PMID:[Osteoporosis, bisphosphonates and jaws osteochemonecrosis]. 1894 74

They are commonly used to treat osteoporosis and other diseases that involve osteoclast-mediated bone resorption, including Paget's disease and multiple myeloma. Their use in treating osteonecrosis of the femoral head has been studied and theoretically holds promise. There are complications associated with these medications, however, including the development of osteonecrosis in the jaw.
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PMID:Bisphosphonates and osteonecrosis: potential treatment or serious complication? 1935 7

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


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