Bisphosphonates: Mechanism of Action and Role in Clinical Practice

Abstract

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

Effect of alendronate on the mandible and long bones: an experimental study in vivo

“…B isphosphonates are synthetic analogues of pyrophosphate and are widely used in the treatment of diverse bone metabolic disorders (1)(2)(3). According to the literature, these drugs exert an anticatabolic effect by altering osteoclast recruitment, differentiation and activity, and/or by stimulating apoptosis (4-6), thus causing a decrease in bone resorption and turnover (1)(2)(3).…”

“…Their anticatabolic effect (1-3) and high affinity for bone (1,2) make them first-choice drugs for the treatment of disorders such as osteoporosis (1,3) and Paget's disease (1). They are also used in young patients (8,9) to treat a number of diseases, including osteogenesis imperfecta (OI) (1,(8)(9)(10)(11), juvenile osteoporosis (12), and fibrous dysplasia (13).…”

“…Based on their chemical structure, bisphosphonates can be classified as non-nitrogen-containing and nitrogen-containing bisphosphonates (1,2). The latter, which include alendronate (ALN), are the most frequently used bisphosphonates at present.…”

“…According to the literature, these drugs exert an anticatabolic effect by altering osteoclast recruitment, differentiation and activity, and/or by stimulating apoptosis (4-6), thus causing a decrease in bone resorption and turnover (1)(2)(3).…”

“…They are also used in young patients (8,9) to treat a number of diseases, including osteogenesis imperfecta (OI) (1,(8)(9)(10)(11), juvenile osteoporosis (12), and fibrous dysplasia (13).…”