CTX as a Marker for BRONJ

In the article¹ titled C-Terminal Cross-Linking Telopeptide as a Serologic Marker for Bisphosphonate-Related Osteonecrosis of the Jaw, a condensed version² of which was published in print Issue 4 of JCDA, the author presents a case report involving the treatment of a patient with multiple myeloma who had previously been treated with intravenous (IV) bisphosphonates.

We would like to congratulate the author for the treatment results and the quality of the figures provided. However, we disagree with the author’s conclusions to the effect that “… patients with low CTX values should not be indefinitely categorized as ‘high risk’…”.¹  As mentioned in the introduction of the article, the use of CTX to assess the risk of potential osteonecrosis of the jaw is highly controversial, and no professional association (e.g., American Association of Oral and Maxillofacial Surgeons , Canadian Association of Oral and Maxillofacial Surgeons, Professional Association of Oral and Maxillofacial Surgeons of Quebec) recommends this test for stratifying the risk of developing this complication.^3,4 The case presented in the article demonstrates a high risk given the patient’s pharmacological history (oncological-dose zolendronate and corticosteroids), independent of the CTX value.

The author also proclaims that the patient was treated “on the basis of the expert panel recommendations for patients receiving bisphosphonate therapy…”.¹ However, the recommendations cited by the author refer to patients treated with oral bisphosphonates, and do not apply to this particular case.⁵  Moreover, more recent recommendations exist.⁶  We believe it is risky to formulate a scientific opinion based on a case report, and is in fact, contrary to the principle of evidence-based medicine.

The Author Responds

Cite this as: J Can Dent Assoc 2013;79:d174

I would like to thank Drs. Bouchard and Fortin for their letter and would put forth the following clarifications. As the abridged print version of my article¹ contained only one case to pique readers’ interest, it may be possible to draw incorrect or incomplete conclusions, namely that intravenous (IV) bisphosphonate (BP) patients should not be considered as high risk. I would encourage readers  to read the full-text online version of the article², which provides a greater examination of the subject matter.

The focus of the article was to evaluate current findings in the literature on the effectiveness of CTX as a predictor for bisphosphonate-related osteonecrosis of the jaw (BRONJ). The conclusion was that very few studies showed any positive correlation, and that in general, it has not been found to be a particularly successful testing method. In this, Drs. Bouchard and Fortin indicated agreement by stating that it is not endorsed by any of the organizations mentioned.

The statement “patients with low CTX values should not be indefinitely categorized as ‘high risk’” was meant to reinforce that CTX alone is insufficient in determining risk, and consequently a course of treatment, and that emphasis should be placed on medical history, length and route of BP usage, concurrent medication, etc. As we both seem to agree that CTX is unreliable and controversial, this statement remains consistent with the findings in the literature.

They correctly mention that most consensus papers focus on oral BP usage. However I have not found any which state that implants are contraindicated for past IV BP users for the duration of their lifetime. While it is true that patients in this population have a higher risk compared to the general population, I also emphasized that this should not necessarily become a lifetime static label. Furthermore, the AAOMS position paper³ suggest that cessation of IV BP in the long term may reduce future risk for BRONJ development. The CAOMS consensus paper⁴ mentions that evidence-based guidelines exist to minimize invasive procedures on patients currently on IV BP. The patients presented in the 2 case vignettes in my article have markedly different IV BP usage histories, and therefore present with different relative risks. The AAOMS position paper³ states that oncology patients receiving IV BP 4 to12 times per year should not receive dental implants, while the patient in case vignette #2 only received IV BP for a total of 3 months.

The presentation of 2 different case vignettes aimed to demonstrate that treatment provided did not rely solely on CTX results, but rather on a variety of factors. No recommendations were made to the reader regarding indications or contraindications for treatment. As I concluded, “treatment should not be determined by the result of a single test alone. Good clinical judgment and a thorough review of the medical history remain the most effective means of determining appropriate treatment.”²