8 Bisphosphonates and Bone

Dental Press Implantology, 2014

he use of bisphosphonates induces clinicians to fear and care. hese reactions are associated with controversy resulting from lack of deep knowledge on the mechanisms of action as well as lack of a more accurate assessment of side efects. here is no scientiic evidence demonstrating that bisphosphonates are directly involved with etiopathogenic mechanisms of osteonecrosis and maxillary osteomyelitis. heir use is contraindicated and limited in cases of dental treatment involving bone tissue. Nevertheless, such fact is based on professional opinion, case reports, and personal experience or experiment trials with failing methods. Additional studies will always be necessary. However, deep knowledge on bone biology is of paramount importance to ofer an opinion about the clinical use of bisphosphonates and their further implications.

2000

Bisphosphonates are primary agents in the current pharmacological arsenal against osteoclastmediated bone loss due to osteoporosis, Paget disease of bone, malignancies metastatic to bone, multiple myeloma, and hypercalcemia of malignancy. In addition to currently approved uses, bisphosphonates are commonly prescribed for prevention and treatment of a variety of other skeletal conditions, such as low bone density and osteogenesis imperfecta. However, the recent recognition that bisphosphonate use is associated with pathologic conditions including osteonecrosis of the jaw has sharpened the level of scrutiny of the current widespread use of bisphosphonate therapy. Using the key words bisphosphonate and clinical practice in a PubMed literature search from January 1, 1998, to May 1, 2008, we review current understanding of the mechanisms by which bisphosphonates exert their effects on osteoclasts, discuss the role of bisphosphonates in clinical practice, and highlight some areas of concern associated with bisphosphonate use.

2012

Bisphosphonates are synthetic analogs of naturally occurring pyrophosphates, and they inhibit bone resorption and therefore improve bone mineral density by decreasing bone turn over. For this reason, it has a wide application in oral diseases, such as oral cancer, breast cancer, osteogenesis imperfecta, fibrous dysplasia, hypercalcemia etc. But this drug has its own adverse effects. Osteonecrosis of the jaws is a major complication associated with long-term use of bisphosphonates. We aimed to summarize the structure of bisphosphonates, its applications, adverse effects, prevention and implications in dental management. The purpose of this review is to identify what new information has been gained over the past ten years and to provide opinion of its implications in dental management.

Brazilian Dental Science, 2013

ABSTRACT The bisphosphonates are synthetic drugs used for treatment of neoplasms and bone, Paget’s disease and more reason for excitement in cases of postmenopausal osteoporosis. These drugs present some known side effects, however, a new complication with oral manifestation was recently identified, called Osteonecrosis. When this necrosis of the bone bases is associated to the use of Bisphosphonates, it is named Osteonecrosis by Bisphosphonates. The type of bisphosphonate, route of administration, and duration of treatment with these drugs seem to have direct relation with the incidence of osteonecrosis associated with bisphosphonates. The aim of this work was to present a review of the last five years about the use of bisphosphonates, the available bisphosphonate groups in the Brazilian market emphasizing those used in the treatment of Osteonecrosis, and exploring possible diagnostic aspects of the disease from image Diagnostics. It is concluded the impact of current world life stimulates new research areas focusing on important illnesses, their manifestations, and on searching for better treatment protocols and faster diagnosis protocols, aiming reduce possible treatment unwanted side effects.

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.

Annals of the New York Academy of Sciences, 2006

The discovery and development of the bisphosphonates (BPs) as a major class of drugs for the treatment of bone diseases has been a fascinating journey that is still not over. In clinical medicine, several BPs are established as the treatments of choice for various diseases of excessive bone resorption, including Paget's disease of bone, myeloma and bone metastases, and osteoporosis. Bisphosphonates are chemically stable analogues of inorganic pyrophosphate, and are resistant to breakdown by enzymatic hydrolysis. Bisphosphonates inhibit bone resorption by being selectively taken up and adsorbed to mineral surfaces in bone, where they interfere with the action of the bone-resorbing osteoclasts. Bisphosphonates are internalized by osteoclasts and interfere with specific biochemical processes. Bisphosphonates can be classified into at least two groups with different molecular modes of action. The simpler non-nitrogen-containing bisphosphonates (such as clodronate and etidronate) can be metabolically incorporated into nonhydrolyzable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. The more potent, nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate, and zoledronate) are not metabolized in this way but can inhibit enzymes of the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small GTP-binding proteins (which are also GTPases) such as rab, rho, and rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explain the loss of osteoclast activity and induction of apoptosis. The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. In conclusion, bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, and their mode of action is being unraveled. As a result their full therapeutic potential is gradually being realized.

General dentistry, 2018

23 Despite being synthesized in the late 1800s, bisphosphonates have only been used clinically for the last 5 decades. In fact, on the 50th anniversary of the first clinical use of a bisphosphonate (1968, etidronate disodium), it is interesting to remember that the origin of bisphosphonates stems from dental research. In the 1960s, Procter & Gamble was hoping to develop a topical agent for use against dental calculus. By the end of the decade, their researchers were working with analogs of pyrophosphate, the disphosphonates, which had a similar structural backbone to the former but centered around a –P–C–P– bond instead of a –P–O–P– bond (Figure). Conformationally, in 3 dimensions this structure created a “bony hook,” resulting in a high affinity of these compounds for hydroxyapatite in bone. Following successful treatment of a young girl who had myositis ossificans progressiva and subsequent studies, etidronate (Didronel) was granted regulatory approval in 1977 for several indicati...

The aim of this review is to give an update on the protocols to be followed by the dentists for dental procedures for patients on bisphosphonate therapy. Presently there is an increasing prevalence of patients receiving bisphosphonate therapy. This review has included the pathological effects on alveolar bone, epithelium, variations in healing time, angiogenesis,and the risk factors associated with Bisphosphonate related osteonecrosis of the jaw (BRONJ) development. The consensus management protocols as recommended by experts is presented comprehensively. It is envisaged that dental practitioners should have a better understanding of bisphosphonate therapy and the complications associated with various dental procedures so as to enable them to render care with confidence and to improvethe quality of life of their patients on bisphosphonate therapy.

Dentistry today, 2006

The authors look into the research studies into bisphosphonates, the important classification of drugs for the treatment of bone diseases. Are bisphosphonates safe when used during or around implant treatment? The authors have some good news for us.