Intriguing New Medical/Chemical Journal Article Contends That Medicinal Chemists Or Pharmacologists At The Drug Company Could Have Anticipated Bisphosphonate-Related ONJ And Femur Fracture Cases
(Posted by Tom Lamb at DrugInjuryWatch.com)
In January 2013 the ACS Medicinal Chemistry Letters journal published in print this article, "Using Medicinal Chemistry To Solve an Old Medical Mystery", written by William B. Hinshaw, a medical doctor, and Louis D. Quin, a professor of chemistry.
In essence, this new article suggests there is evidence about how bisphosphonates like Fosamax cause osteonecrosis of the jaw (ONJ) and atypical femur fractures (AFF) which can be found by looking back at the mysterious 19th century industrial disease syndromes of "phossy jaw" and fragile / fractured femurs that affected certain match-stick workers in Europe.
Moreover, the authors indicate a case could be made that there was sufficient chemical and medical information available in the scientific literature which might have served as "notice" of the potential increased risk of the jaw injuries and femur fractures that have been associated with Fosamax (alendronate) as well as the other bisphosphonates used as osteoporosis medications, such as Actonel (risedronate), Boniva (ibandronate), and Zometa (zoledronic acid).
As regards how Merck and the other drug companies could have known about bisphosphonate-related osteonecrosis of the jaw (BRONJ) and atypical traverse subtrochanteric / midshaft low-impact femur fractures (AFF), the authors begin with the late 1950s research of Herbert Fleisch, who selected the bisphosphonic acids (BPs) as candidates that might mimic the action of pyrophosphoric acid (PPi) and might be, also, orally active.
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Moving forward -- and skipping over some of the scientific-knowledge development steps the authors cover in their article -- it is a 1985 U.S. Army study about the smoke from white phosphorus burning in the air which seems to provide some critical information that, at some time during the next ten years, should have caught the attention of the medicinal chemists and/or pharmacologists at Merck involved in bringing Fosamax to the market in 1995. This Army study showed the initial major constituent of the smoke that those match workers in Europe were inhaling was the same pyrophosphoric acids (PPi) which Fleisch was trying to mimic with his new bisphosphonate drugs. Interestingly, it was a scientific competitor of Fleisch who proved, later, that the bisphosphonates and PPi had the same harmful biological effects in animal models.
In the end, this January 2013 ACS Medicinal Chemistry Letters article which looks at two industrial diseases from back in the 19th century in order to explain the cause of serious jaw and femur side effects associated with bisphosphonates like Fosamax is complex for the lay person, and probably controversial among those with chemical or medical training.
But as the authors make clear in this article, there is a remarkable similarity between the two sets of rare and uncommon sets of diseases associated with bisphosphonate medications (namely, osteonecrosis of the jaw and atypical femur fractures) and the exposure of the match workers ("phossy jaw" and fragile femurs) that suggests there might, in fact, be a common cause at work, here.______________________________________________________________________________