Dental Education Australia

The Effect of Bisphosphonate Exposure on Wound Healing After Tooth Extraction

Understanding Bisphosphonate

Since the 1970's, medicines or drugs containing the synthetic compound Bisphosphonate have been used for various bone diseases. Bisphosphonate has been found effective for treatment of bone diseases due to its similar chemical structure to Pyrophosphate, which is a natural by-product of the body’s cellular metabolism. The role of Pyrophosphate in the body is as a regulator of bone resorption. Bisphosphonate drugs, due to its altered structure from Pyrophosphate, have a better binding to bone and thus have found wide use in the treatment of debilitating bone-resorptive diseases.

Bone diseases commonly treated using Bisphosphonate drugs include: Paget's Disease, which is a disease of the bone characterized by excessive bone destruction with unorganized bone repair and healing; Osteoporosis, which is the abnormal rarefaction or thinning of bone; Hypercalcemia of Malignancy, which is an elevation of serum calcium associated with malignant tumors; Multiply Myeloma, which is the malignant neoplasm of bone marrow; and Bony Metastases, which is the spread of cancer to the bone.

Bisphosphonate works against these bone diseases as an anti-resorptive medicine. It slows down, and may even stop, the natural process of bone resorption by osteoclast cell activity. Some studies have also looked into its effect in promoting bone formation by osteoblast cell activity. These effects of Bisphosphonate to bone cells cause an increase in bone density or thickness and bone strength, thereby lowering the risk of bone fractures in patients diagnosed with bone-resorptive diseases.

Drugs Containing Bisphosphonate

The known medicines or drugs that contain Bisphosphonate include:

Fosamax, generic name Alendronate Sodium, which is used to treat osteoporosis and Paget's Disease;

Actonel, generic name Risedronate Sodium, which is used to treat postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, Paget's disease, and to increase bone density in men with osteoporosis;

Boniva, generic name Ibandronate Sodium, which is used to prevent and treat postmenopausal osteoporosis and to aid in preventing spinal fracture; and

Reclast, generic name Zoledronic Acid, which is used to treat postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, osteoporosis in men, and Paget's disease.

These drugs, with the exception of Reclast, are taken orally and can be taken daily, weekly, bi-weekly, or monthly depending on the patient's need as determined by the medical doctor monitoring the patient's bone disease. Reclast is administered intravenously in a clinic or hospital usually once a year. It is important to note that the

reason Bisphosphonate may be administered at long intervals is due to its ability to stay potent in bones for long periods of time, some even reporting a ten-year viability.

Bisphosphonate and Dentistry

It was in the years 2002 and 2003 when the South Australian Oral and Maxillofacial Surgery Unit recorded several patients with the complaint of a non-healing extraction wound in the jaw. Through proper and accurate gathering of patients' medical history, it was determined that these patients complaining of non-healing wounds were on Bisphosphonate medication. It was also noted then that North American Oral and Maxillofacial Surgery literature presented the occurrences of similar cases. There was a serious problem with bone healing after dental surgery in patients taking Bisphosphonate.

The side effects of Bisphosphonate had before been noted as minor. With the discovery of their effect on wound healing after dental extraction or surgery, beginning in September 2004, health care professionals and patients were made aware of a possible major side effect, which is Osteonecrosis.

Osteonecrosis is a disease caused by the lack of or the reduced blood flow to bones, causing the bone to break down faster than its ability to form new bone, and hence leading to bone death. Although Osteonecrosis is commonly found in the hips, knees, shoulders, and ankles, there are also cases in which the maxilla or mandible is involved. This can happen when the jaw bone is exposed through injury or dental treatment and blood supply to this exposed bone is compromised.

Studies of Bisphosphonate in rats revealed that the drugs cause a decrease in blood flow and a decrease in the circulating vascular endothelial growth factor. As it is known that blood is important for tissue healing, this finding suggests that Bisphosphonate may impair tissue healing by compromising adequate blood supply to wounded tissues. This implies the connection between Bisphosphonate and Osteonecrosis of the jaw.

The significance of Bisphosphonate to the tissues of the oral cavity is suggested by Cheng et al. (2005) in their written work about the dental implications of Bisphosphonate. They state that, "It can be hypothesized that patients who have received long-term bisphosphonate therapy may have a compromised blood supply to their maxilla and mandible. When dental extractions are performed on this group of patients, the open bony wound with a compromised healing ability cannot cope with the presence of oral microflora. The extraction wound then becomes infected and progresses into osteomyelitis due to the poor healing ability of the tissues. It then develops into osteonecrosis."

Bisphosphonate and Clinical Practice

As it is established that patients undergoing treatment with Bisphosphonate have impaired wound healing after dental surgery, dentists are recommended to take

precautions in treating such patients. The first step in preventing untoward effects is to properly diagnose the patient. A complete and adequate medical,dental education and dental history is important in order to know if the patient is already exposed to Bisphosphonate drugs or may eventually need to take them.

If the patient has not started taking Bisphosphonate but has the need to, it is recommended that this be delayed until the patient has a good oral health standing. This is to allow all necessary dental procedures, such as restorations, periodontal treatment, endodontic treatment, and even surgery to be accomplished with less risk. If surgery is needed, this should be performed with minimal bone damage and exposure. Antibiotics are also advised as a preventive measure for infection. Note however that the decision to delay Bisphosphonate medication should come from the patient's medical doctor.

If the patient is already under Bisphosphonate therapy, it is advised to avoid surgery or any treatments that can lead to exposure of bone. Antiseptic mouthrinses and antibiotics may be a non-surgical option for lesions. If surgical debridement of bone is needed, a minimal mucoperiosteal flap reflection is advised in order to preserve blood supply to the bone.

Now that studies and clinical cases have shown evidence for the untoward effect of Bisphosphonate to extraction wound healing, dentists should be more cautious in choosing the best treatment plan for their patients. Dentists should also educate the patients in order to get their cooperation in following a preventive treatment plan, which would be safer for them.

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