Use of bisphosphonates in osteoporosis

Abstract

Osteoporosis is the most common bone disease in humans and it can affect people of all ethnic backgrounds, especially older women and men. In osteoporosis, the low bone mass and microarchitectural deterioration of bone tissue lead to enhanced bone fragility and an increased susceptibility to fractures. The process of repair occurs in bone remodeling, which lasts about 6 months. The most common form of osteoporosis, experienced by postmenopausal women, results from reduced estrogen production, which disrupts the fine balance of the bone remodeling cycle as well as bone resorption. Bisphosphonates (BPs) have been the principal anti-resorptive agents used in the therapy of osteoporosis and they work because of two key properties: (1) strong binding to bone due to a high affinity for hydroxyapatite and (2) their ability to inhibit osteoclast function by inhibiting the enzyme farnesyl-diphosphate synthase. The major treatment goal for patients with osteoporosis is to prevent fractures by maintaining or increasing bone mineral density and reducing excessive bone turnover. Bisphosphonates are well tolerated, but, in many cases oral dosing options have failed because some patients suffer severe upper gastrointestinal tolerance problems or esophageal abnormalities. As a consequence, a range of novel BP-dosing options and formulations (intravenous) have been developed to address these varied circumstances.