Osteonecrosis of the jaw and bisphosphonates
Available from: Mario Vicente-Barrero
- "ONJ is known as a devastating side effect of using BPs in the long-term, although in truth, the genesis of this entity has not been proven yet. Ever since it was des-cribed for the first time in 2003 (8,9), there have been more than 1,000 cases discussed in papers, editorials, letters to the editor and scientific congresses, regarding the strong association between ONJ and BPs (13-17), particularly among patients with MM or solid tumor bone metastases. These patients were generally treated with powerful BPs administered intravenously, but the number of osteoporosis patients with oral BP-related ONJ is increasing (18). "
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ABSTRACT: Osteonecrosis of the jaws is a clinical entity described and linked to treatment with bisphosphonates in 2003. Its real incidence is unknown and it could increase due to the large number of patients treated with these drugs, and its cumulative effect on the bone. State of the art knowledge regarding its etiopathogeny, clinical course and suitable treatments is limited. Objectives: To study the clinical characteristics of 44 patients with bisphosphonate-related osteonecrosis of the jaws and the state of their bone mineral metabolism: Bone remodeling state, prevalence of fractures, bone mineral density study, and assessment of the different treatment strategies. Design of the Study: Observational. Information was gathered prospectively through interviews, clinical examinations, additional tests and review of medical records. Results: We studied 16 men and 28 women with a mean age of 64.7 years. Breast cancer was the most frequent underlying disease. Zoledronate was used in 82% of the cases and in the non-oncology group of patients; alendronate was the most frequently used bisphosphonate. The mean duration of the zoledronate and alendronate treatments was 25 months and 88 months respectively. The lower jaw was the most frequent location, and previous exodontias-among the triggering factors known-were the most closely linked to its onset. We found considerable osteoblastic activity in patients suffering from neoplasia, with artifacts present in their bone densitometry and a high percentage of vertebral fractures. Conclusions: According to our results, osteonecrosis of the jaws affects elderly patients. We found a direct relationship between the duration of exposure and the accumulated dose. Other relevant factors are: Poor oral and dental health, corticoids, diabetes and teeth extractions. In essence, it is a clinical diagnosis. Prevention is the best strategy to handle this clinical entity.
Available from: Lorenzo Preda
- "N Engl J Med 2007;/ 356:/ 459Á 68.  Kratz CP, Boll S, Kontny U, Schrappe M, Niemeyer CM, Stanulla M. Mutational screen reveals a novel JAK2 mutation , L611S, in a child with acute lymphoblastic leukemia. Leukemia 2006;/ 20:/ 381Á3. "
Available from: PubMed Central
- "Clinical results after ten-year's administration of alendronate are promising.1,2 However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture3,4 or osteonecrosis of the jaw,5,6 have been reported recently in the literature. The mechanisms behind these events are not yet clear. "
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ABSTRACT: Bisphosphonates have been used to treat osteoporosis for more than ten years. However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture or osteonecrosis of the jaw, have been recently reported in the literature. We investigated the relationships among the mechanical properties of the intact rat femur as well as healing fracture calluses and the intraosseous concentration of pamidronate (ICP), after long-term administration of pamidronate in a rat osteoporosis model.
We performed bilateral ovariectomy in 25 3-month-old female Sprague-Dawley rats. Beginning three months after ovariectomy, disodium pamidronate (0.5 mg/kg) was injected every month. After the six-month administration period, the left femoral shaft was fractured using the closed fracture technique. Five weeks after fracture, 23 rats were euthanized and both femora were removed. We checked the mechanical properties of the intact (right) and fractured (left) femora using a three-point bending technique. Intraosseous concentration of pamidronate was checked by high-performance liquid chromatography.
The mean ICP was 61.8+/-15.7 ng/mg of bone. High ICP decreased the ultimate load to failure, stiffness, and ultimate stress of the intact femora (p=0.015, 0.027, 0.039, respectively). There was a tendency to decrease the ultimate load to failure in the healing callus when the ICP increased (p= 0.183). High ICP decreased the bone mineral density of the femoral head (p=0.005).
High concentrations of pamidronate in intact bone decreased the bone mineral density and weakened the mechanical strength of the rat femora. The mechanical strength of the early healing callus was not correlated with concentration of pamidronate in the bone.
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