Men's Osteoporosis Support GroupBisphosphonate-related osteonecrosis of the jaws J Craniomaxillofac Surg. 2010 Jun 25. [Epub ahead of print]. Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence - a multi-centre study. Otto S and others. PMID: 20580566. This is a large multi-center European study of the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) that was diagnosed between 2004 and 2008. BRONJ is primarily seen in cancer patients receiving high intravenous doses of bisphosphonates (BP). But the authors point out that 37 of 470 cases (7.8%) were in individuals treated for osteoporosis with standard oral therapy. Of importance is that 57% of these cases had none of the risk factors for BRONJ as defined by the American Association of Oral and Maxillofacial Surgery. What they did find is that older individuals and those taking the BP longer duration were at higher risk. For 78% of the individuals their oral BP therapy exceeded three years. They concluded, "The results from this study suggest that the relative frequency of osteoporosis patients on oral BPs suffering from BRONJ is higher than previously reported. There is an urgent need to substantiate epidemiological characteristics of BRONJ in large cohorts of individuals." Editor's comments. This is another Update, one of several on this site regarding Osteonecrosis of the jaws. It can be quite serious and difficult to treat, so it would be laudable if there was greater understanding of the risk. Why does it happen in only a small percentage of those taking bisphosphonates? Are their tests that could be done to predict in advance who is at greatest risk? If so, which ones and who should be tested? What is normal bone formation rate? Here is my summary of a study done in 1988 copied and pasted from a recent Update centered around bone turnover rates: What is normal histomorphometric analysis? In order to interpret the above results, it will be helpful to have a "normal" histomorphometric analysis with which to compare the findings. See: J Bone Miner Res. 1988 Apr;3(2):133-44, Static and tetracycline-based bone histomorphometric data from 34 normal postmenopausal females. Recker RR and others. PMID: 3213608. There are three important comments in this study: 1) "MAR showed a marked decline with age." MAR is mineral apposition rate. 2) "In contrast, the extent of tetracycline-labeled surfaces varied widely without a secular trend. Double-label surface (dLS/BS) ranged from 0.5 to 8.0% and single-label surface (sLS/BS), from 0.5 to 10.5%." 3) "Using only double-label surface to represent mineralizing surface, volume-based bone formation rate (BFR/BV) ranged from 0.7 to 28%/yr, and the remodeling period (Rm.P) varied from 0.28 to 4.5 years." So what stands out to me regarding "normal" bone formation is the huge difference in bone formation rate and remodeling period in these individuals. An individual with a very long remodeling period and a very low volume-based bone formation rate who is started on bisphosphonates for osteoporosis could have severely depressed bone turnover. This even beyond the normal 90-95% rate reduction in bone turnover with bisphosphonates. But I'm unaware of any way to detect these individuals without doing a bone biopsy, obviously not something that could be done routinely when people start taking bisphosphonates. Perhaps biochemical markers in some particular combination might provide some help along these lines. More research is definitely needed to find something that will help prevent BRONJ in susceptible individuals. Drug holidays might be effective prevention as noted in this recent Update. But the recommendation is for, "Patients at mild risk might stop treatment after 5 yr and remain off as long as bone mineral density is stable and no fractures occur. Higher risk patients should be treated for 10 yr, have a holiday of no more than a year or two, and perhaps be on a nonbisphosphonate treatment during that time." So these recommendations don't include the 22% of individuals in the Otto and others study above who got BRONJ with fewer than three years on bisphosphonates. Yet the majority of individuals would have been covered. Only time will tell if such drug holidays would be totally effective at preventing BRONJ. J Oral Maxillofac Surg. 2010 Jul;68(7):1662-6. Oral bisphosphonate-associated osteonecrosis of the jaw after implant surgery: a case report and literature review. Bedogni A and others. PMID: 20561470. This is a case report of a patient who developed BRONJ approximately two years after apparently successful dental implant surgery. The authors report this as the tenth such case according to their literature review. Editor's comments. A recent Update found no cases of BRONJ in 115 female dental implant patients taking bisphosphonates in the period from 1999 to December 2006. This would indicate the risk of BRONJ after implants is low. But, as can be seen from the Bedogni and others study, there is still some risk. So for anyone on bisphosphonate therapy for osteoporosis contemplating dental implants, be sure to discuss all the potential benefits and risks with your dentist before commencing treatment. Particularly for anyone who has been on long-term bisphosphonates, precautions such as a drug holidays might be wise before starting treatment. Particularly, there are times when nothing but an implant will suffice, so the minimal risk of BRONJ is probably warranted. However, if other means of tooth replacement, such as crowns, bridges or removable partial dentures could effectively do the job, that might be a good first choice. Talk to your dentist about these issues before starting implant therapy.
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