implants - international magazine of oral implantology

I overview Fig. 1_Structural formula of pyrophosphate and basic structure of bisphosphonates with the side chains R1 and R2 (Arzneimittelbrief AMB 1998, 32, 41). Fig. 2_Non-nitrogenous bisphosphonates of the first generation (Abu-Id 2010). _Introduction Osteonecrosis of the jaw due to bisphosphonate was first described in 2003. The disease is called bis- phosphonate-related osteonecrosis of the jaw (BRONJ). Dental implants are contraindicated for tu- mour patients under bisphosphonate therapy. In os- teoporosis patients with oral bisphosphonate admin- istration(notexceedingthreeyears),however,therisk of developing osteonecrosis is considered to be very low.Thefollowingworkprovidesanoverview. Menschutkin, a German chemist, was the first to achieve the synthesis of bisphosphonates in 1895. In the beginning, bisphosphonates were mainly used in the textile, fertilizer and oil industries thanks to their ability to inhibit the precipitation of calcium carbon- ate.Inthe1960s,theywereusedasdetergentadditives byHenkelcompany. 1968 was the year of the first medical application of bisphosphonates. The American orthopaedist An- drew Bassett was in charge of three children whose muscleshadcalcifiedinpart.Oneofthethreechildren (16 months old) was in a life-threatening condition, since his respiratory muscles had already been af- fected. Bassett turned to the Swiss physician Herbert Fleisch who had been dealing intensely with bisphos- phonates. The two physicians used the bisphospho- nateetidronateforthecalcifications.Mostofthefresh calcificationsdisappearedwithinafewdays.Sincethe 1980s,bisphosphonateshavefoundwidespreadusein medicine in particular thanks to their bone-strength- eningeffect. _Chemical principles, mode of action and indication Bisphosphonates are derived from pyrophos- phates. On account of their strong affinity to bone, it was assumed that pyrophosphates might be used in vivo to prevent bone resorption. However, since they are inactivated quickly invivo, they were not suitable asadrug.Insearchofsubstanceshavingasimilar,but prolonged effect, scientists came across bisphospho- nates.TheP-O-Pskeletonofthepyrophosphatesisre- placed by a P-C-P skeleton in the bisphosphonates 18 I implants2_2013 OH OH O = P – O – P = O OH OH Pyrophosphate OH OH O = P – C – P = O R1 OH OHR2 Bisphosphonate O- O- O O CH3 O- O- OH Etidronate PP C O- O- O O CI O- O- CI Clodronate PP C Bisphosphonate therapy and osteonecrosis of the jaw Authors_Johannes D. Bähr, Prof. Dr Dr Peter Stoll & Dr Georg Bach, Germany [PICTURE: ©CLIPAREA L CUSTOM MEDIA]