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)

Bisphosphonates are a new theraeutic option in the treatment of bone diseases. They inhibit osteoclastic bone resorption and are established in the treatment of osteoporosis, Paget's disease of bone and especially in tumor bone disease. The effects of pamidronate, clodronate and ibandronate in the treatment of hypercalcemia of malignancy and osteolytic bone disease have been extensively studied. These drugs represent the treatment of choice in hypercalcemia of malignancy. The regular application of bisphosphonates reduces skeletal-related events like pathologic fracture, bone pain or hypercalcemia of malignancy, especially in breast cancer and multiple myeloma. Of great interest are the ongoing studies concerning prophylactic application of bisphosphonates in tumors bearing a high risk for bone metastases, especially since the first results suggest a significant reduction in the development of bone metastases in breast cancer patients.
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PMID:[Biphosphonate therapy in the management of skeletal metastases]. 961 82

The study deals with a total of 72 patients with Plasma cell dyscrasias (PCD) selected on the basis of atypical plasmacytosis in the bone marrow aspirate and radiological evidence of osteolytic lesions. Males(48) outnumbered the females (24). Pathological fracture and paraplegia was the commonest presenting symptom encountered in 38 patients. Electrophoresis of serum for 'M' band and Immunoelectrophoretic analysis of the serum revealed IgG myeloma in 40 patients followed by, IgA myeloma(13), Light chain disease (12) and other variants in remaining seven cases. The urinary Bence Jones proteins were detected in a total of 34 cases and was frequently encountered with IgA myeloma (7 out of 13) compared with IgG myeloma (13 out of 40) when analysed in Disc electrophoresis. Kappa light chain was observed in 21 cases and lambda counterpart in nine cases without any clinical significance. One case of solitary myeloma terminated in characteristic multicentric multiple myelomatosis within a span of six months in the sequential follow up study. We recommend the triangular approach to diagnosis of paraproteinemia with a special emphasis on immunoelectrophoresis for typing multiple myeloma and allied disorders along with disc electrophoresis for the demonstration of urinary Bence Jones protein in the routine set up.
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PMID:Immunochemical studies in multiple myeloma. 971 37

Records of 28 patients with pathologic lesions in the proximal femur treated by implantation of a femoral head and neck replacement prosthesis between 1984 and 1995 were reviewed. Mean clinical followup was 47.8 months in the eight living patients and 15.8 months in the 20 patients who had died. The underlying diagnosis was metastatic disease or myeloma in 22 patients. The most frequently occurring indication for implantation of this device was a pathologic fracture in 26 patients (18 displaced, eight impending), followed by resection and reconstruction in two patients. All femoral components were cemented: 23 were bipolar hemiarthroplasties and five were total hip arthroplasties. Implant survivorship was good (93%), with only two prostheses removed during the followup period, both for infection. However, radiographic analysis revealed increasing lucencies with time, particularly in the most proximal zones, resulting in radiographic failure in an additional case. Deep infection occurred in three cases, leading to resection arthroplasty in two patients. Periprosthetic fractures occurred in three cases, but only one occurred intraoperatively. Despite a high complication rate, the good implant survival during the shortened life span of these patients supports the continued use of femoral head and neck replacement prostheses in this population.
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PMID:Head and neck replacement endoprosthesis for pathologic proximal femoral lesions. 972 76

Multiple myeloma is the malignant proliferation of plasma cells involving more than 10 percent of the bone marrow. The multiple myeloma cell produces monoclonal immunoglobulins that may be identified on serum or urine protein electrophoresis. Bone pain related to multiple lytic lesions is the most common clinical presentation. However, up to 30 percent of patients are diagnosed incidentally while being evaluated for unrelated problems, and one third of patients are diagnosed after a pathologic fracture, commonly of the axial skeleton. Multiple myeloma must be differentiated from other causes of monoclonal gammopathy, including monoclonal gammopathy of undetermined significance, heavy chain disease, plasmacytoma and Waldenstrom macroglobulinemia. Chemotherapy with melphalan-prednisone is the standard treatment for multiple myeloma. Other treatment modalities include polychemotherapy and bone marrow transplantation. Only 50 to 60 percent of patients respond to therapy. The aggregate median survival for all stages of multiple myeloma is three years.
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PMID:Multiple myeloma: recognition and management. 1020 7

We report a patient with an epidermotropic cutaneous T-cell lymphoma which transformed into an anaplastic cutaneous CD30+ T-cell lymphoma. Repeated relapses required prolonged systemic PUVA therapy. Two years after diagnosis, the patient had several episodes of infections of the respiratory tract. Serum electrophoresis now revealed significantly reduced polyclonal immunglobulin production and an additional band in the gamma fraction corresponding to IgG lambda monoclonal gammopathy. Thereafter, the patient suffered a pathologic fracture of the dorsolateral 5th rib on the right side and an accumulation of monoclonal plasma cells in the bone marrow confirmed the diagnosis of multiple myeloma (IgG lambda). Accordingly, 6 cycles of cytoreductive chemotherapy (alkeran, decortin) were given. After one year of steady state disease the patient lost weight and bone pain increased while only a few papular eruptions were detectable. Radiography showed multiple small osteolytic areas. A few months later he died with signs of bone marrow insufficiency.
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PMID:Development of IgG lambda multiple myeloma in a patient with cutaneous CD30+ anaplastic T-cell lymphoma. 1051 78

We report about a rare case of a pathological fracture of the shank following earlier pathological fractures at other locations in a comparatively young female patient with no history of trauma. There were no known diseases other than psoriasis. The shank fracture was treated surgically by osteosynthesis. Osteoporosis, myeloma, or malignancy as causative factors of this fracture could be excluded. Scintigraphy showed an enhancement, especially at the extremities. Other than reactive bone growth, histological examination revealed no further aspects. Laboratory analysis indicated a massive lack of vitamin D3. After transferring the patient to the internal department of our hospital, long-term medication with fumaric acid was determined to be the reason for the osteomalacia of a Fanconi's syndrome. Three months after cessation of these medicaments and treatment with active vitamin D3 metabolites, the patient was free of complaints. The radiographs showed an essential improvement of the demineralization.
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PMID:[Multiple pathological fractures within the scope of DeToni-Debre-Fanconi syndrome after fumarate therapy in psoriasis]. 1141 62

The bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and are now the treatment of choice for the management of hypercalcaemia of malignancy. The incidences of hypercalcaemia and other skeletal complications (bone pain, pathological fracture) remain high despite apparent responses to systemic therapy, with particularly high event rates in women with advanced skeletal metastases of breast cancer. This review focuses on studies addressing the long-term efficacy of bisphosphonates to reduce skeletal complications in breast cancer (5 studies) and multiple myeloma (4 studies), with particular reference to controlled studies of sufficient magnitude and duration to allow confidence in the estimation of efficacy. Bearing in mind the limitations of differences in trial design and the lack of direct studies comparing drugs, adequate exposure to a bisphosphonate reduces the incidence of skeletal complication by 30 to 40% in both breast cancer and multiple myeloma. Oral clondronate and intravenous pamidronate have similar efficacy in both diseases, but the duration of efficacy may differ between drugs. Both agents have shown intriguing survival benefits in subgroups of patients. The numbers needed to treat (NNT) to prevent a skeletal complication during one year are lowest in metastatic skeletal disease in breast cancer (NNT < 8) but also compare very favourably with other disease for patients with recurrent nonskeletal breast cancer or multiple myeloma (NNTs 7 to 31 depending on the complication to be prevented). Treatment costs of both breast cancer and multiple myloma are driven by inpatient and outpatient hospital visits so that bisphosphonate regimens should be developed that reduce both. Further research is required to determine if subgroups of patients can be better identified that will derive particular benefit, or perhaps no benefit at all, from bisphosphonate therapy. It is not known whether more potent bisphosphonates will deliver greater clinical efficacy in the future.
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PMID:The clinical and cost considerations of bisphosphonates in preventing bone complications in patients with metastatic breast cancer or multiple myeloma. 1151 Oct 21

Most patients with multiple myeloma have lytic lesions at multiple sites in the axial skeleton. These lesions commonly give pain and are at risk of pathological fracture, and bony disease is therefore a cause of much morbidity in myeloma. Recent data indicates that the Receptor Activator of NF-kappaB ligand (RANKL) and Osteoprotegerin (OPG) may be central to the local pathogenesis of these lytic lesions. Bisphosphonates may ameliorate some of these abnormalities, and clinically these agents improve the skeletal prognosis in myeloma patients. High dose chemotherapy with autologous stem cell rescue is currently under evaluation in the management of myeloma, though little is known of the effect of this therapeutic modality on the skeleton. Studies using biochemical markers of bone turnover suggest that increased osteoclast activity may be present even in apparent plateau phase of myeloma. High dose chemotherapy with autografting may normalise abnormal bone resorption, though the effect may take several weeks to emerge, and may be paralleled by increased osteoblast activity. The findings provide biochemical evidence that autografting may help normalise the abnormal bone turnover characteristic of myeloma.
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PMID:Bone turnover following autologous transplantation in multiple myeloma. 1200 53

We investigated the incidence of bone lesions in elderly cases of multiple myeloma (MM) and the course of those lesions, and also evaluated the relationships of skeletal symptoms with prognostic factors, and prognosis. The subjects were 146 patients, aged 65 years or more (median age 74, range 65-97 year), who were admitted to 11 institutions between January, 1988 and December, 1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88 patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type in three patients, and non-secretory type in one patient. Bone lesions in elderly MM patients were compared with those in 65 non-elderly MM patients. Skeletal symptoms were noted in 104 patients, and bone pain in 75 patients at the time of diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26 patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in 2 patients and pathologic bone fractures in 53 patients. The occurrence rate of osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion in lumbar vertebrae was higher in elderly patients (58.7%) than that in non-elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71 patients because of the bone lesions. The relationship between the prognostic factors of MM and bone lesions was evaluated. There was a significant difference in the serum Ca level between patients with and without bone pain (P < 0.0001) and between those with and without pathologic bone fracture (P < 0.01). There was a significant difference in the appearance rate of plasma cells in the bone marrow between the patients with and without bone lesions (P < 0.05), between those with and without bone pain (P < 0.01), and between those with and without pathologic fracture (P < 0.05). There was a significant difference in the serum beta 2-microglobulin level between the patients with and without bone pain, and between those with and without pathologic fracture. There were no significant differences in survival times between elderly MM patients with and without bone lesions, bone pain and pathological bone fractures, while significant differences of survival times were found between non-elderly MM patients with and without bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These data suggest that there are some differences in bone lesions between elderly and non-elderly MM patients.
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PMID:[Bone lesions in elderly multiple myeloma]. 1251 15

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41


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