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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates (formerly termed diphosphonates) were first synthesized in the late 1800s; however, their clinical use has been relatively recent. The bisphosphonates' affinity for hydroxyapatite crystal surface led Procter and Gamble to test these compounds in dental, then medical applications. With key input from university researchers, this led to the medical use of the first bisphosphonate, etidronate disodium in 1968 to treat a young patient with myositis ossificans progressiva. Further clinical research led to widespread medical application for the bisphosphonate class including use as a diagnostic in radionuclide bone imaging agents, treatment of osteoporosis, Paget's disease of bone, hypercalcemia of malignancy and metastatic bone disease. The historical development of bisphosphonates provides an excellent example of how observations and knowledge obtained at the basic science level were applied and successfully tested in the clinic. The end result of these efforts has provided health care professionals with diagnostic and therapeutic tools to improve the lives of patients.
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PMID:Historical perspectives on the clinical development of bisphosphonates in the treatment of bone diseases. 1739

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

The skeleton is one of the most common sites of metastasis in patients with lung cancer. It has been reported that the incidence of bone metastases in lung cancer patients is approximately 30-40%, and the median survival time (MST) of patients with such metastases is 6-7 months. Metastatic bone disease leads to various complications or skeletal related events (SREs), including pain, pathologic fracture, vertebral deformity and collapse, spinal cord compression, and hypercalcemia of malignancy. These events often lead to rapid deterioration in quality of life (QOL). The fundamental treatment for bone metastasis from advanced lung cancer is disease control by systemic chemotherapy. So the prevention and treatment of bone metastases is mainly dependent on an effective treatment against lung cancer itself. As a direct treatment for bone metastases, radiation therapy, surgery and bisphosphonates are the main ways.
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PMID:[Bone metastases in lung cancer]. 1837 26

Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and represent the treatment of choice in disorders associated with accelerated bone resorption. They are widely used in the management of Paget's disease of bone and hypercalcemia of malignancy. Over the past few years, evidence has been accumulating for a beneficial effect of these agents in tumor-induced osteolytic bone disease and in established osteoporosis. Bisphosphonates may also play a useful though limited role in the medical management of hyperparathyroidism and heterotopic ossification.
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PMID:Role of bisphosphonates in metabolic bone diseases. 1840 29

Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral bisphosphonates are used mainly to treat PMO and are not associated with significant nephrotoxicity. In contrast, nephrotoxicity is a significant potential limiting factor to the use of intravenous (IV) bisphosphonates, and the nephrotoxicity is both dose-dependent and infusion time-dependent. The two main IV bisphosphonates available to treat hypercalcemia of malignancy and osteolytic bone disease in the United States are zoledronate and pamidronate. Patterns of nephrotoxicity described with these agents include toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis, respectively. With both of these agents, severe nephrotoxicity can be largely avoided by stringent adherence to guidelines for monitoring serum creatinine prior to each treatment, temporarily withholding therapy in the setting of renal insufficiency, and adjusting doses in patients with pre-existing chronic kidney disease. In patients with PMO, zoledronate and pamidronate are associated with significantly less nephrotoxicity, which undoubtedly relates to the lower doses and longer dosing intervals employed for this indication. Ibandronate is approved in the US for treatment of PMO and in Europe for treatment of PMO and malignancy-associated bone disease. Available data suggest that ibandronate has a safe renal profile without evidence of nephrotoxicity, even in patients with abnormal baseline kidney function.
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PMID:Bisphosphonate nephrotoxicity. 1868 74

While intravenous (IV) bisphosphonates are well established in managing metastatic bone disease and hypercalcemia of malignancy, oral bisphosphonates are the primary treatment for postmenopausal osteoporosis. The availability of a well-tolerated, effective, IV bisphosphonate regimen for postmenopausal osteoporosis would increase physicians' options, allowing treatment of patients who cannot tolerate oral therapy, for whom oral bisphosphonates should be avoided or patients who are unable to comply with the oral dosing recommendations. Ibandronate is a potent, nitrogen-containing bisphosphonate, with proven efficacy and good tolerability when administered intermittently either orally or intravenously. Preclinical experience in animal models with IV ibandronate indicated that it had good renal tolerability. These data are supported by clinical pharmacology studies. Prolonged follow-up of patients receiving intermittent IV 15-30 second injections of 0.5-3 mg IV ibandronate has demonstrated no clinical evidence of renal toxicity in patients with postmenopausal osteoporosis. What is seen in controlled studies is not always the case in uncontrolled studies, however, no reports of renal failure have been received in post-marketing surveillance of >500,000 patients receiving IV ibandronate infusions in various indications including metastatic breast and prostate cancer. The good renal tolerability of IV ibandronate in patients with osteoporosis with glomerular filtration rates >30 mL/minute and without renal co-morbid conditions is reassuring.
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PMID:Renal tolerability of intermittent intravenous ibandronate treatment for patients with postmenopausal osteoporosis: a review. 1921 Aug 86

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

Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia. Compared with the hypercalcemia of malignancy, hyperparathyroidism tends to be associated with lower serum calcium levels (< 12 mg/dL) and a longer duration of hypercalcemia (more than 6 months). The hypercalcemic symptoms are usually fewer and subtle. Hyperparathyroidism tends to cause kidney calculi, hyperchloremic metabolic acidosis, and the characteristics of metabolic bone disease osteitis fibrosa cystica, but no anemia. In contrast, hypercalcemia of malignancy is typically rapid in onset, with higher serum calcium levels, and more severe symptoms. Patients so affected show marked anemia, but they never have kidney calculi or metabolic acidosis. Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia. In hyperparathyroidism, serum parathyroid hormone levels will be elevated. In other cases, the high serum calcium concentration usually results in suppression of parathyroid hormone. Treatment of hypercalcemia should be started with hydration. Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload. Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia. For long-term control of severe or symptomatic hypercalcemia, the addition of biphosphonate is typically required. Among intravenous bisphosphonates, zoledronic acid or pamidronate are the agents of choice. Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases. Dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure.
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PMID:Hypercalcemia: an evidence-based approach to clinical cases. 1939 81

Lung cancer is one of the most common cancers diagnosed worldwide. As the disease progresses, patients with lung cancer can develop metastasis to the bone. However, because early-stage bone disease may be asymptomatic, bone metastases often go undiagnosed, resulting in delayed initiation of treatment to prevent skeletal complications. In the absence of bone-targeted therapies, patients with metastatic bone disease are at increased risk for potentially debilitating skeletal-related events (SREs) including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and the requirement for surgery or radiation therapy to bone. The majority of patients with bone metastases from lung cancer will develop SREs, and this number is expected to increase with the improvement of primary therapies that are prolonging the lives of patients. Zoledronic acid is the only bisphosphonate that has been extensively studied in patients with bone metastases from lung cancer, and it has demonstrated efficacy in delaying the onset and reducing the risk of SREs in this setting. Preventing SREs with zoledronic acid may preserve the quality of life and functional independence of these patients. Recent exploratory analyses of a phase III study in patients with bone metastases from lung cancer or other solid tumors revealed that zoledronic acid also normalizes biochemical markers of bone metabolism and may also improve survival in specific patient subsets. Additional ongoing clinical trials are assessing further benefits and antitumor activity of zoledronic acid in the adjuvant setting in the prevention of bone metastases in patients with lung cancer.
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PMID:Skeletal disease contributes substantially to morbidity and mortality in patients with lung cancer. 1963 38

Bone metastases are associated with considerable morbidity and can result in skeletal-related events (SREs), including pathologic fractures, the need for palliative radiotherapy, spinal cord compression, the need for surgery to bone to prevent or treat a pathologic fracture or spinal cord compression, and hypercalcemia of malignancy. Such SREs have been associated with decreases in survival and increases in healthcare costs. Skeletal morbidity and bone pain from metastases can also reduce patients' functional capacity and undermine their quality of life. Patients who develop bone metastases from advanced cancers commonly receive bisphosphonates to not only delay the onset of SREs and reduce their frequency but also provide clinically meaningful palliative effects for bone pain. Ongoing research may lead to improvements in skeletal health monitoring and management for patients with malignant bone disease.
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PMID:Bone metastases from advanced cancers: clinical implications and treatment options. 1994 68


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