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)

The majority of the patients with advanced prostate carcinoma have painful skeletal metastases, which are responsible for significant skeletal morbidity and disability. Most of these metastases are osteosclerotic, but it has been shown that the abnormal osteoblastic bone formation within metastases is preceded by osteoclastic activation, which appears to be associated with bone pain. This provides the rationale for using bisphosphonates, which are powerful and selective inhibitors of osteoclastic bone resorption. Several bisphosphonates have been shown to be clinically useful for the treatment of several conditions characterized by abnormal osteoclastic bone resorption, including Paget's disease, primary hyperparathyroidism, myelomatosis, and skeletal metastases. Its efficacy in relieving pain in patients with skeletal metastases due to prostate carcinoma has been confirmed in a few studies. The bisphosphonate clodronate was extensively investigated in the study unit. When infused intravenously i.v. (300 mg/day) relief of bone pain become appreciable within 3 days, sometimes preceded by a transient pain flare. These clinical results are very consistent and the residual pain usually is of extraosseous origin. Thus, with regard to pain of strictly bone origin, unresponsive patients are quite rare. Oral administration also is effective, but due to its limited intestinal absorption the effective dose is on the order of 1600-3200 mg/day. These doses usually are well tolerated, but they may be a problem for severely ill patients. Furthermore, the efficacy of treatment becomes apparent only after a few days. Thus, oral clodronate usually is adopted as a continuation of an i.v. course. The duration of the i.v. therapy should be individualized, but usually the more prolonged the treatment the longer the duration of the effect. For practical reasons, clodronate is infused daily for 5 days (Monday-Friday) and the treatment course is repeated at the time of any significant recurrence. The oral continuation prevents or delays the recurrence of bone pain in most patients, but in some patients this therapy has to be integrated occasionally with i.v. infusion. The duration of the effect for the same bioavailable dose is somewhat related to the degree of malignancy of the primary tumor. In an uncontrolled study, the author also evaluated the effectiveness of alendronate given either i.v. or orally. A single infusion of 5 mg alendronate i.v. produces roughly the symptomatic effect of 5 i.v. infusions of 300 mg clodronate. Alendronate, 40 mg orally/day, was effective in reducing bone pain in 11 of 12 patients with bone metastases due to prostate carcinoma but who were not confined to bed. In some patients with prostate carcinoma and a diffuse metastatic invasion of the skeleton, there is indirect biochemical and histologic evidence of osteomalacia. This can be aggravated by bisphosphonate administration because of the transient striking prevalence of osteoblastic activity over bone resorption, which also occasionally causes the appearance of symptomatic hypocalcemia. Therefore, the use of large oral supplements of calcium is recommended, particularly at the start of therapy. It is conceivable that these calcium supplements also may be able to improve the final clinical outcome of the bisphosphonate therapy. In conclusion, administration of large doses of bisphosphonates is one of the most cost-effective palliation treatments for patients with prostate carcinoma with bone metastases, both as first-line therapy and in the long term. With appropriate doses, a large proportion of patients can be maintained free of bone pain until death. Studies of the ability of lower doses to prevent skeletal morbidity in patients without metastases or with asymptomatic bone lesions are warranted.
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PMID:Bisphosphonates in prostate carcinoma. 936 35

Osteochemonecrosis of the jaws is a well described side effect of bisphosphonate therapy. Bisphosphonates are non metabolised analogues of pyrophosphate that are capable of localizing to bone, slowing both rate of growth and rate of dissolution therefore reducing the rate of bone turnover. Although the exact mechanism is not clear but it has been established that bisphosphonates target osteoclast, inhibiting their function in several ways: There are two types of bisphosphonates. The first are oral preparations of bisphosphonates, which include Alendronate and Risedronate. They are indicated for the treatment of osteoporosis. They are considered as lower risk of osteochemonecrosis. The second are administered intravenously. Pamindronate is a first generation bisphosphonate; 90 mg administered intravenouly over 2-24 hours every 3-4 weeks. The next generation of intravenous bisphosphonate is Zoldronic acid, which is more effective than Pamidronate in controlling hypercalcaemia of bone and reducing the skeletal related events in patients with metastatic breast cancer, multiple myeloma, hypercalcaemia of malignancy, paget's disease and bone metastasis from prostate and lung cancer.
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PMID:Osteochemonecrosis of jaws and bisphosphonates. 1749 45

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