Dental side effects of bisphosphonates

Aug. 24, 2006
Hygienists need to be aware of potential side effects and how the drugs can affect dental treatment.

by Howard M. Notgarnie, RDH, MA

In the past two years, several cases of osteonecrosis in the maxilla and mandible have been associated with bisphosphonates. This is particularly ironic, since this class of medication is used to protect bone from osteoporosis. Paget's disease is also treatable with bisphosphonates.(1) Recent studies found bisphosphonates are showing promise in laboratory bone graft studies(2) and clinical cases of osteonecrosis of the femoral head.(3)

Bisphosphonates have two mechanisms of action. "Simple bisphosphonates that closely resemble pyrophosphate" cause cell destruction of osteoclasts. Aminobisphosphonates prevent production of proteins that signal osteoclast activity.(4) Robb-Nicholson reports medications to prevent osteoporosis include the orally administered alendronate, risedronate, ibandronate, injectible zoledronic acid, and pamidronate. This class of drug provides some protection from osteoporosis by inhibiting osteoclast activity, which breaks down bone, while allowing osteoblasts, which build bone, to continue their function. Together, these two types of cells are important for renewing and remodeling bone throughout life. Most cases of bisphosphonate-associated osteonecrosis occurred after dental surgical procedures and in patients taking chemotherapy and steroids for cancer with metastasis to bone. Although the mechanism of this complication is unknown, a theory suggests osteoclastic activity stimulates the formation of osteoblasts. Without completing the cycle of bone regeneration, old bone tissue loses its blood supply and dies. Likewise, after an extraction, insufficient stimulation of osteoblasts leads to a nonhealing site.(5) Another theory, suggested by Woo, Hellstein, and Kalmar is that inhibition of osteoclastic activity prevents turnover of bone, thus repair of microscopic injuries. The weakened physiology of the bone makes it susceptible to necrosis.(1)

Bisphosphonates are also used for treatment of cancer. Bamias, Kastritis, and Bamia are cited finding 6.7 percent of 250 people treated for cancer with bisphosphonates developing jaw osteonecrosis, including 10 percent of those treated for myeloma developing this side effect. Zoledronic acid was associated with the highest incidence of osteonecrosis. An increased number of doses and duration of treatment also increased the incidence. Patients in the study were invariably taking other medications as well. About three-fourths of those developing osteonecrosis had dental extractions subsequent to bisphosphonate treatment.(6)

Schulte explains how chronic diseases of the gastrointestinal tract can result in osteoporosis due to reduced absorption of vitamin D, effects of chronic inflammation on bone metabolism, and effects of corticosteroids used to treat gastrointestinal diseases. Cytokines and corticosteroids increase bone resorption by altering the balance between receptor activator of NF-kappa B (RANK) ligand and osteoprotegerin (OPG). The above inflammatory products increase the amount of RANK ligand, which upon contact with receptors on osteoclasts causes more of those cells to grow. OPG inhibits RANK ligand's binding to receptors on osteoclasts, so the increased ratio of RANK ligand to OPG causes an increase in osteoclastic activity. As with other causes of osteoporosis, treatment may include a dietary regimen and bisphosphonates. Patients are screened for osteoporosis by measuring bone density determined through X-ray absorption "at the spine, proximal femur, and distal radius." Differential diagnosis of the cause of low bone density includes typical blood tests, testosterone levels, and protein electrophoresis.

A meta-analysis of postmenopausal osteoporosis suggested vitamin D, bisphosphonates, and estrogen receptor modulators were effective in reducing vertebral fracture risk, but calcium, calcitonin, fluoride, and hormone replacement were not effective. Schulte recommends considering these effects for osteoporosis secondary to gastrointestinal disease as well. Unfortunately, GI disease can reduce absorption of bisphosphonates as well.(4)

Woo, Hellstein, and Kalmar explain that aminobisphosphonates treat tumors by destroying cells, preventing invasion and adhesion of tumor cells, preventing formation of blood vessels, and increasing activity of T cells involved in fighting tumors. Jaw osteonecrosis seems to be associated with trauma. Most cases occur after extractions and are located near the mylohyoid ridge. Of those not associated with extractions, they are commonly associated with dentures or exostoses. Chronic periodontitis also increases the risk of osteonecrosis development. Osteonecrosis will appear as exposed yellow-white bone. Sinus tracts and painful ulcers may also be present.(1)
Woolerton describes "Signs and symptoms of osteonecrosis of the jaw

• Infection of the gums

• Drainage from the gums

• Poor gum healing

• Numbness in the jaw, or a sensation of heaviness

• Jaw pain or swelling

• Exposed bone"(7)

While there is no universally accepted protocol, Woo, Hellstein, and Kalmar provide the following …

Recommended protocol:

Patients planning to begin bisphosphonate therapy or have recently started therapy for osteoporosis:

• Eliminate oral infection and areas at high risk of infection

• Receive routine preventive and therapeutic care

• Minimize periodontal inflammation

Patients with long-term use of bisphosphonates, especially intravenous:

• Attempt treatment with nonsurgical approaches and antibiotics

• If surgery is needed, minimize bone manipulation

Patients with osteonecrosis:

• Consult images with more detail than radiographs

• Avoid injuring adjacent structures when removing dead bone

• Use disinfectant oral rinses

• Use systemic antibiotics and analgesics

• Wear a protective stent

• Consider discontinuing bisphosphonates until necrosis is under control(1)

Implications of the above recommendations for dental hygiene practice include …
Prior to bisphosphonate treatment:

• Gather an updated medical history

• Carefully screen conditions and potential problems treatable by a dentist

• Ensure that the periodontal condition is as healthy as possible with dental hygiene care

• Refer to a periodontist or oral surgeon

• Apply topical fluoride

• Stress importance of completing care to avoid complications

During bisphosphonate therapy:

• Consult with oncologist or prescribing physician

• Aggressive nonsurgical periodontal therapy may be needed to avoid periodontal surgery

• Consider oral rinses before and after dental hygiene treatment

Patients with osteonecrosis:

• Consider learning to read advanced imaging techniques

• Consult with physician and oncologist

• Refer to oral surgeon

• Consider systemic antibiotics pre- and post-treatment

There is an increasing use of bisphosphonates in the population. Dental hygienists need to be aware of the conditions for which these medications may be taken to be alert to the possibility that a client might start using one of these drugs. We also need to be aware of the potential side effects of these medications and how they might affect the treatment we provide.

Howard M. Notgarnie, RDH, MA, practices dental hygiene in Colorado, and has eight years' experience in official positions in dental hygiene associations at the state and local levels.

1Woo SB, Hellstein JW, Kalmar JR. Systematic review: bisphosphonates and osteonecrosis of the jaws. Annals of Internal Medicine 2006; 144(10):753-761.
2Tàgii M, Astrand J, Westman L, Aspenberg P. Alendronate prevents collapse in mechanically loaded osteochondral grafts: A bone chamber study in rats. Acta Orthopaedica Scandinavica 2004; 75(6):756-761.
3Lai KA, Shen WJ, Yang CY, SHAO CJ, HSU JT, LIN RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. Journal of Bone and Joint Surgery 2005; 87(10):2155-2159.
4Schulte CMS. Review article: Bone disease in inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 2004; 20(4):43-49.
5Robb-Nicholson C. By the way, doctor. Harvard Women's Health Watch December 2005; 13(4):8.
6Bamias A, Kastritis E, Bamia C. Osteonecrosis of the jaw in cancer
after treatment with bisphosphonates: Incidence and risk factors. Journal of Clinical Oncology; 2005; 23:8580-8587. Cited in Anonymous. Treatment—Complications. Breast Cancer Mar. 4, 2006; 4:26-27.
7Woolerton E. Patients receiving intravenous bisphosphonates should avoid invasive dental procedures. Canadian Medical Association Journal; 2005; 172(13):1684.