[AF] Bifosfonatos y osteonecrosis del maxilar.

Carmen Martinez Vera carmenmartinezvera en gmail.com
Vie Ene 18 20:00:51 CET 2008

Te envio la contestacion que nos mando el Dr. Jose Sanchis
Cervera, hematologo, a una consulta similar.

Carmen Martinez Vera

Como Hematologo yo recomiendo comenzar los implantes    finalizado el trato con bifosfonatos porque si por desgracia sucede una    "NECROSIS AVASCULAR MAXILAR" el cuadro clinico es "escalofriante y por    necrosis cae el implante y todos los dientes.Bien es verdad que este cuadro lo    estamos viendo en pacientes con mieloma en trto con acido    zoledronico.

Saludos Cordiales:
Dr.Jose Sanchis    Cervera
Jefe de Hematologia y Hemoterapia
 Em at home : bloodies at ono.com
 Em at work    : sanchis_joscer at gva.es
 Phone:    699-155-171

Bisphosphonates are a family of drugs used in the treatment    and prevention of post-menopausal osteoporosis and that induced by corticoids,    in Paget's disease and hypercalcaemia associated with neoplasia. They are also    indicated in the treatment of osteolytic lesions and the pain caused by them.    For this reason, they are widely used drugs in Haematology for patients    diagnosed with Myeloma. The most common bisphosphonates used in this disease    are pamidronate and zoledronic acid.
The mechanism of action of the bisphosphonates is based on    their binding with hydroxyapatite which in turn inhibits ostoclastic bone    resorption. Berenson1 observed that the use of pamidronate improved    survival and decreased bone complications. This and other studies2, 3 were carried out to support the indefinite    use of bisphosphonates.

Mandibular osteonecrosis has been reported as one of the    secondary effects of bisphosphonates. In 2003, the first possible association    between treatment with bisphosphonates and the appearance maxillary avascular    necrosis was reported4. A series of risk factors have been described    for the appearance of complications. A history of radiotherapy, the use of    corticoids or treatment with thalidomide and dental manipulation appears to be    involved as triggering factors in the majority of cases. The risk of    osteonecrosis increases with dental extractions and poor oral hygiene, in such    a way that on the bone being exposed to the flora, it becomes super-infected    producing pain, inflammation, infection with suppuration and, finally bone    necrosis.

There is no effective treatment for mandibular osteonecrosis,    therefore it is a cause of increased morbility in patients. As an effective    treatment has not been established, microbiological studies must be carried    out and the use of antibiotics is recommended for treating the infections    (amoxicillin combined with clavulanic acid in the case of normal flora), along    with mouthwashes with 0.12% chlorhexidine. In patients in whom conservative    treatment has not been effective, surgical intervention must be planned to    remove the area of necrotic bone5.

Since mandibular osteonecrosis was first described, more than    400 cases have been notified, which has led to a review of the concept of    indefinite treatment, a maximum of 2 years of bisphosphonates treatment    currently being recommended in patients with Myeloma.

As has happened with other drugs, this secondary effect was    not detected in clinical trials, being notified later when a higher number of    patients had been subjected to treatment. In September 2004 the pharmaceutical    laboratory that marketed pamidronate and zoledronic acid issued a letter    including avascular necrosis as a possible secondary effect.

As a result of the notification of cases of osteonecrosis in    patients with Myeloma treated with bisphosphonates, several committees made up    of expert panels have issued a series of recommendations for the prevention,    diagnosis and treatment of osteonecrosis6. Patients with Myeloma who are going to    receive treatment with bisphosphonates must always be informed of the    possibility of this secondary effect occurring. It is essential that the    Odontologist carries out an evaluation of the patient who is going to receive    treatment with bisphosphonates, and during the treatment periodic visits must    be made to treat caries and periodontal diseases.

It is also essential that all Haematologists have sufficient    information about this complication to prevent it, and in cases of the    suspected appearance, act rapidly to reach a correct diagnosis and apply the    ideal treatment.


1. Berenson JR, Lichtenstein A, Porter      L, Dimopoulos MA, Bordoni R, George S ET AL. Long-term pamidronate treatment      of advanced multiple myeloma patients reduces skeletal events. Myeloma      Aredia Study Group.l Journal Clinical Oncology 1998; vol 16:      593-602.

2.- Berenson JR, Lichtenstein A, Porter L et al.      Efficacy of pamidronate in reducing skeletal events in patients with      advanced multiple myeloma. N Engl J Med 1996; 334:488-493. Available at: http://content.nejm.org/cgi/content/full/334/8/488

3.- Berenson JR, Rosen LS, Howell A et al.      Zoledronic acid reduces skeletal-related events in patients with osteolytic      metastases. Cancer 2001; 91: 1191-1200

4.- Wang J, Goodger NM, Pogrel MA. Osteonecrosis      of the jaws associated with cancer chemotherapy. J Oral Maxillofac Surg      2003; 61:1104-7

5.- Jiménez Soriano Y, Bagan JV. Los bifosfonatos,      nueva causa de osteonecrosis maxilar por fármacos: situación actual. Med      Oral Patol Oral Cir Bucal 2005; 10 Suppl2: E88-91).

6.- Lacy M, Dispenzieri A, Gertz M et al. Mayo      Clinic Consensus Statement for the Use of Bisphosphonates in Multiple      Myeloma. Mayo Clin Proc. 2006; 81: 1047-1053. Available at: http://www.mayoclinicproceedings.com/pdf%2F8108%2F8108sa.pdf

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