Current Pharmaceutical Design - Volume 16, Issue 27, 2010

Bisphosphonates are stable analogues of the naturally-occuring inorganic pyrophosphate and unlike PPi, they are resistant to hydrolysis due to a carbon atom bridging the two phosphonate groups. Whether the first bisphosphonates formerly termed diphosphonates were synthesized in the late 1800s, their clinical applications have been relatively recent. In the 1960s, H. Fleisch and R.G.G. Russell identified the inorganic pyro Read More

Bisphosphonates are widely used in the treatment of diseases involving excessive bone resorption, such as osteoporosis, cancer- associated bone disease, and Paget’s disease of bone. They target to the skeleton due to their calcium-chelating properties, where they primarily act by inhibiting osteoclast-mediated bone resorption. The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolise Read More

The nitrogen containing bisphosphonates (N-BP) are the drug of choice for treating disease characterised by resorption of bone such as osteoporosis and metastatic bone disease. The overall mechanism of action is achieved through a combination of precise targeting to the bone environment and an extremely potent inhibition of a vital enzyme in an essential metabolic pathway. This targeting to bone is achieved t Read More

Bisphosphonates are a class of drugs developed over the past three decades for the treatment of metabolic bone diseases with high bone turnover, such as Paget's disease, tumor associated osteolysis and osteoporosis. The exceptional pharmacokinetic profile of bisphosphonates makes them very suitable and safe drugs for the treatment of bone diseases, because, by conventional administration, osseous tissue a Read More

Bone tumours can be dissociated in two main categories: i) primary bone tumours (benign or malignant) including mainly osteosarcoma and other sarcomas. ii) and giant cell tumour and bone metastases originate from others cancer (Breast, prostate, kidney cancer, etc). These tumours are able to destroy or/and induce a new calcified matrix. However, the first step of bone tumour development is associated with an inductio Read More

Bisphosphonates are standard treatment for cancer-induced bone disease, a common feature of many advanced malignancies. Traditionally used to inhibit bone turnover and reduce the risk of skeletal-related events, there is now increasing pre-clinical evidence that these agents may also affect tumour burden and disease progression. In particular, combining bisphosphonates with chemotherapeutic agents has been demo Read More

Certain primary tumours including breast and prostate cancers have a particular propensity for metastasis to bone. Metastatic bone disease can have significant impact on morbidity and mortality of cancer patients. Skeletal-morbidity (spinal cord compression, hypercalcaemia, fracture, need for radiotherapy and surgery to bone) can be effectively reduced by bisphosphonates, a class of antiresorptive drugs. They are also effe Read More

Bisphosphonates, especially nitrogen-containing bisphosphonates (N-BPs), are widely used to block bone destruction in cancer patients with bone metastasis because they are effective inhibitors of osteoclast-mediated bone resorption. In addition to their antiresorptive effects, preclinical evidence strongly suggests that N-BPs have anticancer activity. Some of the activities associated with N-BPs are observed in human γδ T Read More

Cancer is a major leading cause of death in the western world (following heart diseases). It poses an enormous burden on patients and society with a major impact on healthcare and economy. Once cancers have spread to the skeleton, treatment options are predominantly limited to palliation, treatment of hypercalcemia and prevention of pathological fractures. Despite the elaborate efforts of modern medicine to improve trea Read More

Multiple myeloma is an incurable B cell neoplasm caused by the monoclonal expansion of malignant plasma cells in the bone marrow, often resulting in devastating bone disease. For over 2 decades bisphosphonates have been successfully used to treat the tumourinduced bone disease associated with multiple myeloma. This review will focus on preclinical studies and investigations in patients with multiple myeloma that Read More

Since their development 30 years ago, bisphosphonates are now one of the standard therapy in the management of osteoporosis. Improvements in terms of anti-resorptive potency have leaded to new molecules available either orally or intravenously, from weekly to yearly administration. Overall tolerance of bisphosphonates is good with regards to the risk of mandibular necrosis, not comparable with those observed in ca Read More

Bisphosphonates are widely use for pathologies such as osteoporosis, Paget's disease or bone metastasis. However, their potent antiresorptive properties open new therapeutic opportunities for other conditions associated with an increased focal or systemic bone remodelling. Moreover, apart from their antiresorptive activity, bisphosphonates could also have others properties through a specific analgesic or anti-inflamma Read More