Pharmacological diversity among drugs that inhibit bone resorption

Pyrophosphate: a key inhibitor of mineralisation

“…Secondly, pyrophosphate does not inhibit bone resorption, whereas this is the key pharmacological action of BPs when used to treat clinical disorders characterised by excessive resorption [100]. BPs are very effective drugs with more than 40 years of clinical use, and have proven to be remarkably safe, with an excellent benefit to risk ratio [109]. Despite this there is a considerable literature on the possible adverse effects, namely osteonecrosis of the jaw (ONJ) and atypical femoral fractures.…”

Pathophysiology and therapeutic options in osteogenesis imperfecta: an update

“…93 There was an increase in lumbar spine and total hip BMD over the 5 years and a significant reduction in the risk of fractures of hip (47% reduction, P,0.001), spine (23% reduction, P,0.001), and nonvertebral (23% risk reduction, P,0.001). 43,93 Applicability to the collagen defect in OI remains to be determined.…”

“…43 In an animal model, the cathepsin K monoclonal antibody (Odanacatib) effectively suppressed bone resorption. 92 A Phase III randomized, placebo-controlled trial assessed the effect of Odanacatib on fracture risk over 5 years of treatment in 16,713 women with osteoporosis aged 65 years or older.…”

“…BPs have strong affinity for bone mineral, particularly at sites of increased bone turnover. 43 In OI, the response to BP therapy differs between children and adults. BP treatment is generally efficient during childhood due to high bone turnover; however, after puberty there is a decrease in bone turnover, which limits the effectiveness of BP in decreasing fracture rate.…”

“…Third-generation BPs are nitrogen-containing analogs of pyrophosphate, which inhibit osteoclast bone resorption by interfering with the mevalonic acid pathway and protein prenelation. 43 Bone formation is subsequently increased as osteoblastic bone formation completes mineralization at sites of active bone formation (transients). BPs have strong affinity for bone mineral, particularly at sites of increased bone turnover.…”