Response to – A commentary on “Suppurative osteomyelitis, bisphosphonate induced 1 osteonecrosis, osteoradionecrosis: a blinded histopathologic comparison and its 2 implications for the mechanism of each disease” by R.E. Marx and R. Tursun [Int. J. Oral. Maxillofac. Surg. 41 (3) (2012) 283–289]

Dr. Kalmar’s Letter to the Editor makes several incorrect assertions and misleading remarks as follows:

  • 1.

    Dr. Kalmar criticizes our microscopic interpretations yet uses references that actually support it. Particularly, the reference entitled “Giant Osteoclast Formation and Long-term Oral Bisphosphonate Therapy” where the authors identify that alendronate (Fosamax) promotes the accumulation of apoptotic osteoclasts and their detachment from bone. Several other papers have noted the same toxic effects of alendronate as we have.

  • 2.

    Dr. Kalmar also criticizes our blinding of the glass slides and suggests that comorbidities and the clinical setting should have been considered. I totally disagree. The very intent of blinding a histopathologic study is to prevent bias due to a foreknowledge of prejudicial clinical factors. The consistency of our histopathologic results confirms the root cause of bisphosphonate induced osteonecrosis to be osteoclast dysfunction and death regardless of the same and different comorbidities that exist in each of these three groups and among the individual within each group.

  • 3.

    Dr. Kalmar also criticizes our research design by suggesting that we use a more complex statistical analysis. This would be a valid criticism only if indeed we incorporated the myriad of suggested comorbidities and concomitant drugs that patient’s could have taken in each of our three groups. In consultation with the biostatics department at the University of Miami Miller School of Medicine, they felt that the readers of IJOMS are perfectly capable of interpreting the validity of our findings by themselves without the illusion of credibility generated by complex statistics.

  • 4.

    Dr. Kalmar concludes by asserting that our future studies should include “a collaborator with experience and a board certification in pathology”. This is a curious statement requiring several comments: First, since this drug complication and this article discusses osteonecrosis of the jaws only, Dr. Kalmar would have been better off to suggest an oral and maxillofacial pathologist. Second, throughout all of the osteoporosis studies accomplished by Merck Co. Inc, consultants as well as other bisphosphonate companies and their consultants none included a board certified pathologist or board certified oral and maxillofacial pathologist. Had they done so, I believe they would have agreed with the conclusions regarding the direct correlation of bisphosphonates to the disease osteopetrosis as I and others reached several years ago. In fact, this seems to have been confirmed in September 2011 when the FDA instructed Merck Co to provide a more adequate warning to professionals who prescribed these drugs. Third, none of the Merck Co. adjudicators looked at or requested histopathology of available specimens in the initial 428 cases plus sent to them for comparison to any disease. It is curious now that Dr. Kalmar criticizes the first independent group to do so. Fourth, numerous other authors without board certification in pathology have interpreted histopathology in the literature related to the bisphosphonate induced osteonecrosis we are experiencing and has spawned over 1300 publications and 14 specialty position papers. In my own (REM) defense, I have personally been a member in the American Academy of Oral and Maxillofacial pathology for the past 30+ years, I have already published extensively on the histopathology of all three of the diseases pertinent to this article, I have also published two editions of a major textbook on oral and maxillofacial pathology. This text also received the Medical Writers Book of the Year Award upon its publication. I and my coauthor are very confident in our data and conclusions. We present our images and findings to the readers of IJOMS for their own interpretation.

Competing interests

None.

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Jan 24, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Response to – A commentary on “Suppurative osteomyelitis, bisphosphonate induced 1 osteonecrosis, osteoradionecrosis: a blinded histopathologic comparison and its 2 implications for the mechanism of each disease” by R.E. Marx and R. Tursun [Int. J. Oral. Maxillofac. Surg. 41 (3) (2012) 283–289]
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