Bísphosphonates: Mechanism of Action and Role in Clinical Practice

Vojnosanitetski pregled, 2014

Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 2009

Journal of Oral and Maxillofacial Surgery, 2004

Oral and Maxillofacial Surgery Clinics of North America, 2014

Bisphosphonates, synthetic analogues to inorganic pyrophosphates found in the bone matrix, inhibit bone resorption. Bisphosphonates and their related effects on the jaw have been established since 2001. Bisphosphonates are used in many clinical situations to treat conditions causing bone resorption, such as metastatic bone disease (particularly seen with multiple myeloma, breast cancer, and prostate cancer), osteoporosis, hypercalcemia, and Paget disease. Bisphosphonates, synthetic analogues to inorganic pyrophosphates found in the bone matrix, work by inhibiting bone resorption. 1 They do not repair existing bone damage, but help prevent formation of new lytic lesions. They do so through several mechanisms of action, including attaching to hydroxyapatite-binding sites on bony surfaces to impair osteoclast activity, decreasing the development of osteoclast progenitor cells, and promoting apoptosis of osteoclasts. Normal bone growth and maintenance involve a tightly coupled process of bone resorption by osteoclasts and deposition by osteoblasts.

Journal of Oral and Maxillofacial Surgery, 2009

Bisphosphonates were first described more than 40 years ago as analogs of naturally occurring inorganic pyrophosphates. Pyrophosphates are easily dissociated by hydrolysis, whereas bisphosphonates are completely resistant to hydrolysis-one of the main reasons bisphosphonates accumulate in the bone matrix and have a long half-life. 1 It has been shown that bisphosphonates inhibit the recruitment of osteoclasts, reduce their resorptive activity on the bone surface, and shorten their life cycle-thus resulting in overall diminished bone resorption. 2,3 In addition, bisphosphonates disturb intraosseous angiogenesis through inhibition of endothelial cells. Clinically, bisphosphonates are used to treat malignancy-related osteolysis (eg, bone metastases of prostate or mammary carcinoma, multiple myeloma, etc), hypercalcemia caused by hyperparathyroidism, Paget's

… Ciência (Journal of …, 2009

Bisphosphonates have been widely prescribed for treatment of diseases characterized by intense bone resorption. These drugs have also been associated with a serious side effect, avascular osteonecrosis of the jaws. The authors present a literature review on bisphosphonates, focusing on their pharmacological features and their reported association with jaw osteonecrosis. The morbidity and lack of treatment response of this condition are serious facts to be considered when prescribing bisphosphonate therapy. The risk-benefit relationship needs to be seriously analyzed, and the treatment pros and cons should be explained to the patient. If the therapy with bisphosphonate is indicated, rigorous oral health adequacy must be performed and periodic evaluation of oral conditions is mandatory. At this moment, caution in treatment seems to be the best way to approach bisphosphonate users.

Dental Press Implantology, 2015

Journal of Oral and Maxillofacial Surgery Official Journal of the American Association of Oral and Maxillofacial Surgeons, 2009

The American Journal of Medicine, 2009

Osteonecrosis of the jaw (ONJ), a condition characterized by necrotic exposed bone in the maxillofacial region, has been reported in patients with cancer receiving bisphosphonate therapy, and rarely in patients with postmenopausal osteoporosis or Paget disease of bone receiving such therapy. In the absence of a uniform definition, the American Academy of Oral and Maxillofacial Surgeons (AAOMS), the American Society for Bone and Mineral Research (ASBMR), and other groups have established similar diagnostic criteria for bisphosphonate-related ONJ, which is more commonly reported in patients with advanced malignancies with skeletal metastases who receive higher doses, and is more rarely reported in patients with osteoporosis and Paget disease who receive lower doses. However, a critical review of the literature reveals that the etiology of ONJ remains unknown, and to date no direct causal link to bisphosphonates has been established. Despite an increased awareness of ONJ and recent improvements in preventive strategies, patients and physicians alike continue to express concern about the potential risks of bisphosphonate treatment in both oncologic and nononcologic settings. Although much remains to be learned about this condition, including its true incidence in various patient populations, its pathophysiology, and optimal clinical management, evidence to date suggests that the positive benefits of bisphosphonates in patients with malignant bone disease, osteoporosis, or Paget disease outweigh the relatively small risk of ONJ.

Romanian Journal of Rheumatology

This article aims to establish, on the basis of medical literature and of the authors’ experience, whether bisphosphonates still have a role in treating skeletal diseases, with increased bone resorption. The effects of bisphosphonates on the bone tissue, as well as the diseases in which they are recommended and the benefits obtained are reviewed. Possible side effects are emphasized, both the immediate ones, which are better known and the late ones, occurring after a long-term administration. It is shown that the benefit/risk ratio remains favorable. The conclusions highlight the fact that nowadays bisphosphonates still have an important place in the treatment of skeletal diseases.