Keywords

Osteoporosis; Bone sickness; Resorption; Bisphosphonates

Description

Bisphosphonates are the most frequently prescribed treatments for osteoporosis in both postmenopausal women and men. They inhibit bone resorption by osteoclasts and indirectly reduce bone formation associated with resorption without direct effects on osteoblast bone formation. Several of the nitrogen-containing bisphosphonates (NBPs) have been shown in prospective placebo-controlled studies over a period of up to 4 years to reduce the risk of fractures of the spine, proximal femur, and non Bisphosphonates -vertebral fractures. While reduced risk of fractures implies better bone strength and bone strength cannot be measured in individual patients, current models show that decreased bone resorption leads to both better bone microarchitecture and increased bone mass. Both the effects contribute to bone strength. All bisphosphonates share the PCP structure "bisphosphonate", which is responsible for their affinity for hydroxyapatite on bone surfaces, while the chemistry of the group attached to the central carbon leads to their inhibition of osteoclast-mediated bone resorption. The pharmacokinetic profiles of all NBPs are similar and differ significantly from most other drugs. Oral bioavailability is 1% and must be administered on an empty stomach or by intravenous (IV) infusion. BPs in the blood spread rapidly to bone surfaces is excreted in the urine. The half-life of BPs on bone surfaces is 3-5 weeks, where they inhibit osteoclasts that form resorption gaps on BP-coated surfaces. Its long half-life on the bone surface allows for weekly, monthly and even yearly treatment regimens. BPs is not metabolized and can be incorporated into new bone where they are not pharmacologically active unless a subsequent round of bone remodeling results in their resorption. When PA treatment is discontinued, bone resorption increases in two phases. The first phase occurs over weeks or months when the concentration on the bone surface decreases. If enough PA has been incorporated into the new bone formed during the previous treatment, this bisphosphonate can be released and again inhibit bone resorption. The second phase of increased resorption after treatment occurs gradually as the blood pressure in the bone decreases (the estimated half-life with the bone is approximately 5 years). Upper gastrointestinal symptoms are the only common side effects of oral bisphosphonates and may require the use of an intravenous dosage form. Less common side effects are musculoskeletal pain, which begins several months after starting treatment and disappears when treatment is stopped. Two rare possible side effects (osteonecrosis of the jaw and atypical femoral fractures) limit widespread patient acceptance and lead to a "drug vacation" after 3-5 years of treatment to reduce the risk of side effects. Controlled clinical trials are needed to determine the persistence of both reduced risk of fracture and the risk of adverse events (including atypicalfemur fractures) after discontinuation of long-term bisphosphonate therapy (3-5 years), either at the same dose or with a lower dose is a continuous dose in order to develop an evidence-based approach to drug use during the holidays.