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Bisphosphonate complications

2007-07-31

Precaution of Dental Complications in Patients receiving Bisphosphonates
By Michael T Brennan, DDS, MILS

The role of bisphosphonates in reducing or preventing skeletal morbidity associated in cancer patients is well-documented. This includes a reduction in bone fractures and the management of hypercalcemia related to bone metastasis. The mechanism appears to be related to inhibition of osteoclast function, which results in decreased bone resorption. In addition, a potential anti-tumor effect has been reported with IV bisphosphonates. (1)

Although less potent oral bisphosphonates have been utilized for many years for the treatment of osteoporosis, the use of IV bisphosphonates provides sufficient dosages necessary for treatment of skeletal complications from bone metastasis. Common IV bisphosphonates include pamidronate (Aredia®) and zoledronic acid (Zometa®), and have been recommended for the following: hypercalcemia of malignancy; multiple myeloma; and bone metastasis from breast, prostate or lung.

Several cases of painful bone exposure of the jaws have been reported in patients taking IV bisphosphonates, and in rare cases with oral bisphosphonates. In the largest reported cohort of 119 patients with osteonecrosis followed by Marx and colleagues, 26 percent were receiving pamidronate, 40 percent zoledronic acid, 30 percent pamidronate followed by zoledronate, and 3 percent had received the oral bisphosphonate alendronate (Fosamax®). The average duration of bisphosphonate exposure was 14 months for pamidronate, nine months for zoledronate, 12 months for pamidronate followed by zoledronate, and three years for alendronate. Thirty-one percent of patients presented with asymptomatic exposed bone, while 69 percent had painful exposed bone. Sixty-eight percent of cases appeared on the mandible, 28 percent on the maxilla, and 4 percent on both the mandible and maxilla with 88 percent of cases involving posterior teeth.

Twenty-five percent of cases have been reported to occur spontaneously, while 38 percent of cases were related to tooth extraction, 29 percent with existing periodontal disease, 4 percent after periodontal surgery, and three percent after dental implant placement. The incidence of osteonecrosis for patients receiving IV bisphosphonates appears to range between 5-13 percent, with the incidence increasing after six months of therapy. (1,2)

Dental management for patients treated with IV bisphosphonates primarily focuses on prevention of osteonecrosis. Prior to the start of IV bisphosphonate therapy, patients should have a thorough clinical and radiographic dental examination with elimination of infectious sources including extraction of compromised teeth, optimization of periodontal health, caries removal, eliminating sharp restorations, and evaluation of prosthodontic appliances. (1'2)

For patients who have already started IV bisphosphonates, concern for development of osteonecrosis must be considered before invasive procedures are started. Extractions are not recommended unless necessary, and limiting extractions to class III mobile teeth may be prudent. Root canal therapy for teeth with extensive decay and amputation of the crown may be indicated. (2) The oral cavity should be carefully examined for areas of exposed bone.

The treatment of osteonecrosis has had very limited success. Debridement, flap procedures to cover exposed bone, or bone contouring have led to larger areas of exposed bone without resolution. Hyperbaric oxygen therapy has been unsuccessful. Therefore treatment is focused on pain symptoms and management of secondary infections.

Management of pain symptoms may include smoothing rough edges if soft tissue irritation is involved. Fabrication of a splint to cover rough areas is another viable option. (1) With signs of secondary infection, the use of penicillin V-K 500 mg, 4x/d and 0.12 percent chiorhexi-dine is indicated. For refractory cases, metronidazole 500 mg 3x/d can be added to the previous regimen. For penicillin allergic patients, Marx has recommended ciprofloxacin 500mg 2x/d and metronidazole 500 mg 3x/d. More advanced infections may require IV antibiotics. (2)

Resolution of exposed areas of bone is an uncommon outcome for patients on long-term IV bisphosphonates. A follow-up of 97 patients with osteonecrosis at one year or more demonstrated 82 (85 percent) patients were pain free with management recommendations previously described, but still with exposed bone. Close follow-up of patients on IV bisphosphonates who experience areas of exposed bone is essential to ensure stability of this chronic complication. The half life of IV bisphosphonates in bone has been suggested to be as high as 10 years, therefore resolution of exposed bone may be limited. Further investigations of this complication will be necessary to better establish risk factors and other treatment options for this patient group.

I. Migliorati CA et al., Managing the care of patients with bisphosphonate-associated osteonecrosis. JADA. 2005;136:1658-1668.

2. Marx RE et al., Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63:1567-1575.



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