Bisphosphonate-associated bone necrosis

from Wikipedia, the free encyclopedia

Bisphosphonate-associated pine necroses , engl. bisphosphonate-associated osteonecrosis of the jaw (BONJ, ONJ) is necrosis of the jawbone that occurs more frequently in patients who have previously been treated with bisphosphonates . The trigger is usually a dental or oral surgery procedure. However, spontaneous BONJ have also been described. Bisphosphonates inhibit bone loss and are used against osteoporosis and against bone metastases .

These jaw necrosis are similar to infected osteoradionecrosis (IORN) in patients after radiation therapy for head and neck cancer . Some of them show difficult courses. Patients with tumor disease or immunosuppression are more often affected than osteoporosis patients . The BONJ is almost exclusively associated with intravenously administered amino bisphosphonates.

Bisphosphonates

Bisphosphonates are pyrophosphate analogues in which the oxygen is substituted by carbon in the POP bond. This means that no enzymatic hydrolysis takes place in the body. Bisphosphonates have a high affinity for the bone surface, especially in the area of ​​resorption lacunae. They inhibit the osteoclasts and thereby lead to reduced bone resorption. If there is an increased rate of bone breakdown due to osteoporotic remodeling processes or bone metastases, a very effective reduction in osteoclastic processes can be achieved through the use of bisphosphonates. Bisphosphonates act as a mechanical barrier between the bone surface and osteoclasts. Furthermore, there is an increased apoptosis rate of the osteoclasts. In this way, bisphosphonates effectively inhibit the progressive bone loss. In addition - probably via the normal activity of the osteoblasts - there is usually a certain increase in bone density of around 2 to 3% per year, at least during the first three years of treatment.

Bisphosphonates have a very long pharmacological half-life in bones, some of which is more than ten years, which means that the indication for the use of this active ingredient should be made strict. This group of active ingredients is currently approved for the treatment of patients with overt bone metastases from tumors or with postmenopausal osteoporosis.

Pathogenesis of Pine Necrosis

The factors underlying bone necrosis in patients receiving systemic bisphosphonate therapy are still largely unknown. The mechanism of osteoclastic and osteoblastic inhibition is discussed, which may not only lead to a reduced rate of osteolysis, but also damage the regenerative capacity of the bone through osteoblast depression.

Since it was first described, the BONJ has developed into a serious medical problem, especially in patients who have been given intravenous nitrogen-containing derivatives (so-called aminobisphosphonates) due to cancer. In this patient group, prevalences of BONJ of over 18% have been described. But also in patients with oral bisphosphonate intake without an underlying malignant disease, such as B. osteoporosis, this disease occurs, but with a significantly lower probability of about 0.1%.

prevention

Experts have determined risk factors based on the cases known so far:

  • Pine necrosis was mainly observed when - as is usual with cancer patients - the drugs were used in high doses.
  • So far, damage to the jawbone has only occurred with nitrogen-containing drugs (as opposed to nitrogen-free drugs).
  • The risk for patients who take bisphosphonates in tablet form is lower than with regular infusions into the vein.
  • Major interventions such as root treatment, the use of implants and tooth extractions increase the risk of jaw damage.

Before prescribing therapy with intravenous bisphosphonates, a dentist should be consulted, who will plan the necessary treatment measures and carry them out before starting bisphosphonate therapy. Dental rehabilitation does not have to be carried out to the radical extent that patients with head and neck cancer do before radiation. This is also due to the lack of risk of radiation caries . However, teeth that are not worth preserving, root remains and partially retained wisdom teeth should be removed. Clinically and radiologically symptomless, root-treated teeth can be left under annual radiological control. Teeth with chronic apical periodontitis and radical cysts are better removed, as there is a risk of failure after apical resection. Not to be underestimated is the possibility of a BONJ caused by denture pressure points; Patients with removable dentures should therefore be checked regularly.

If surgical interventions are necessary in patients undergoing bisphosphonate therapy, this is done under antibiotic protection and as gentle (atraumatic) a procedure as possible. The indication for tooth extraction must be made very strictly. Extraction sockets are plastically covered with epiperiosteally prepared soft tissue flaps. The sutures are removed no earlier than ten days after the operation. The antibiotics must also be administered by this day. Wisdom teeth that are completely bony impacted are left. Interventions in the sense of surgical tooth preservation are to be avoided. Intensive caries and periodontal prophylaxis is also recommended for these patients. A regular follow-up check is carried out accordingly, especially in the case of people with removable dentures. Implant placement is strictly contraindicated in patients in this group.

literature

  • S3 guideline bisphosphonate-associated jaw necrosis of the German Society for Oral and Maxillofacial Surgery (DGMKG). In: AWMF online (as of 2012)
  • MH Abu-Id, Y. Acil, J. Gottschalk, T. Kreusch: Bisphosphonate-associated osteonecrosis of the jaw. In: mouth-jaw-face shield. 2006; 10, pp. 73-81.
  • MM Bornstein, K. Oberli, E. Stauffer, D. Buser: Bisphosphonate-associated Osteonecrosis of the maxilla. A case report with literature review. In: Switzerland Monthly Dental Medicine. 2006, 116, pp. 1035-1042.
  • F. Granziani, S. Cei, F. La Ferla, E. Cerri, A. Itro, M. Gabriele: Association between osteonecrosis of the jaws and chronic high-dosage intravenous bisphosphonates therapy. In: J Craniofac Surg. 2006 Sep; 17 (5), pp. 876-879.
  • KA Grötz: Prophylaxis and therapy of the consequences of therapeutic radiation in the mouth, jaw and face area. In: Quintessence. Berlin 2001.
  • D. Kademani, S. Koka, MQ Lacy, SV Rajkumar: Primary surgical therapy for osteonecrosis of the jaw secondary to bisphosphonate therapy. In: Mayo Clinic Proc. 2006 Aug; 81 (8), pp. 1100-1103.
  • CA Migliorati, MA Siegel, L. Elting: Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. In: The Lancet Oncology . 2006 Jun; 7 (6), pp. 508-514.
  • JU Piesold, B. Al Nawas B, KA Groetz: Osteonecrosis of the jaws by long term therapy with bisphosphonates; Mouth jaw face shield. 2006 Sep; 10 (5), pp. 287-300.
  • D. Ruehlmann, AC Kuebler: Maxillary osteomyelitis after therapy of systemic osteolytic processes with bisphosphonates. In: Quintessence. 2005; 56 (7), pp. 679-682.
  • G. Sanna, L. Preda, R. Bruschini, M. Cossu Rocca, S. Ferretti, L. Adamoli, E. Verri: Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer. In: Annals of Oncology . 2006 Oct; 17 (10), pp. 1512-1516.
  • C. Von Poznak, C. Estilo: Osteonecrosis of the jaw in cancer patients receiving intravenous bisphosphonates. In: Oncology (New York) . 2006 Aug; 20 (9), pp. 1053-1062.
  • A. Wutzl, G. Eisenmanger, M. Hoffmann, C. Czerny, D. Moser, P. Pietschmann, R. Ewers: Osteonecrosis of the jaws and bisphosphonate treatment in cancer patients. In: Wien Klin Wochenschr. 2006 Aug; 118 (15-16), pp. 473-478.

Web links

Individual evidence

  1. A. Barasch, J. Cunha-Cruz et al. a .: Risk Factors for Osteonecrosis of the Jaws: a Case-Control Study from the CONDOR Dental PBRN. In: Journal of Dental Research. 90, 2011, p. 439, doi: 10.1177 / 0022034510397196 .