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How menopause affects oral health, and what we can do about it

Cleveland Clinic Journal of Medicine. 2009 August;76(8):467-475 | 10.3949/ccjm.76a.08095
August 1, 2009|Cleveland Clinic Journal of Medicine
Maria Clarinda A. Buencamino, MD;Leena Palomo, DDS, MSD;Holly L. Thacker, MD, CDD
Author and Disclosure Information

Maria Clarinda A. Buencamino, MD
Women’s Health Institute, Cleveland Clinic

Leena Palomo, DDS, MSD
Assistant Professor of Periodontology, Director of Predoctoral Periodontics, Case Western Reserve University School of Dental Medicine, Cleveland, OH

Holly L. Thacker, MD, CDD
Director, Center for Specialized Women’s Health, Women’s Health Institute, Cleveland Clinic; Associate Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Maria Clarinda A. Buencamino, MD, Internal Diagnostic Department, E13, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail buen-cam@ccf.org

Dr. Palomo has disclosed that she has received honoraria for speaking and teaching from Procter and Gamble.

Dr. Thacker has disclosed that she has received honoraria for speaking and teaching from Bayer, Novartis, Procter and Gamble, Sanofi-Aventis, Ther-Rx, Upsher-Smith Laboratories, and Wyeth companies, and the Alliance for Better Bone Health.

ABSTRACTAfter menopause, women become more susceptible to periodontal disease. We believe the problem is due in large part to estrogen deficiency with resulting bone loss and inflammatory processes. Osteoporosis and periodontal disease are best diagnosed early so that treatment can be started sooner and fractures and tooth loss can be prevented.

KEY POINTS

  • Physicians should be vigilant for dental problems and should encourage their patients to practice good oral hygiene and to seek regular dental care.
  • Available information suggests that hormone therapy and bisphosphonate drugs may be developed to protect against alveolar bone loss and perhaps slow the progression of periodontal disease.
  • Bisphosphonate-associated osteonecrosis of the jaw is rare, and most of the reported cases have been in cancer patients who received high doses of bisphosphonates intravenously and who had other risk factors for it.

BISPHOSPHONATES PROTECT BONE

In the skeleton

Bisphosphonates, the most commonly prescribed therapy for osteoporosis, inhibit systemic bone resorption and reduce the incidence of vertebral and nonvertebral fractures. Among the bisphosphonates, alendronate (Fosamax), risedronate (Actonel), and intravenous zoledronic acid (Reclast) have been shown to reduce the risk of both hip and vertebral fractures, whereas ibandronate (Boniva) has only been shown to decrease the risk of vertebral fracture.36 Specific findings:

  • In the Fracture Intervention Trial,37 alendronate reduced the risk of vertebral fracture by 47% and hip fracture by 51% in women with low bone mineral density and previous vertebral fractures.
  • In the Hip Intervention Program,38 risedronate decreased the risk of hip fracture by 40% in postmenopausal women 70 to 79 years old with osteoporosis, but not in those 80 years and older, who are at high risk of falls. Risedronate also reduced vertebral fracture risk by 49% after 3 years of treatment.39
  • In the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial,40 annual infusion of zoledronic acid after a hip fracture reduced the rates of new clinical vertebral and nonvertebral fractures and death from all causes.

In the jaw

Not surprisingly, recent studies suggest that bisphosphonates slow the resorption of alveolar bone of the maxilla and mandible as well. Alendronate and risedronate, in particular, have been noted to improve periodontal status.41–43 Findings:

  • In a cross-sectional study by Palomo et al,41 postmenopausal women with low bone density using risedronate for at least 3 months showed significantly less plaque accumulation, less gingival inflammation, lower probing-depth measurments, less periodontal attachment loss, and greater alveolar bone levels.
  • In a double-blind, controlled, prospective study by Rocha et al,42 6 months of alendronate therapy significantly improved periodontal disease as assessed radiographically and clinically in 40 postmenopausal women with established periodontal disease.
  • Jeffcoat et al43 reported that 2 years of alendronate treatment significantly reduced alveolar bone loss relative to placebo in patients with low mandibular bone mineral density at baseline but not in those with normal baseline mandibular bone mineral density.

DO BISPHOSPHONATES CAUSE OSTEONECROSIS OF THE JAW?

Figure 5. Osteonecrosis of the jaw.
Despite these benefits, there has been much concern about bisphosphonate-associated osteonecrosis of the jaw (Figure 5). Osteonecrosis of the jaw is a rare disorder characterized by exposure and loss of bone in the maxillofacial complex that is resistant or refractory to conventional therapy (reviewed by Carey and Palomo44). Most of the information on an association with bisphosphonates comes from case reports involving cancer patients who received high intravenous doses and who had other risk factors for jaw disease.45–48

The intravenous bisphosphonates most commonly used to treat hypercalcemia of malignancy, multiple myeloma, or metastatic bone disease are47:

  • Pamidronate (Aredia) 90 mg infused over 2 to 24 hours every 3 to 4 weeks
  • Zoledronic acid (Zometa) 4 mg infused over 15 minutes monthly.

The doses of bisphosphonates indicated for the treatment of osteoporosis are much lower,1 eg:

  • Alendronate 70 mg by mouth once a week
  • Risedronate 35 mg by mouth once a week or 150 mg once a month
  • Ibandronate 150 mg by mouth once a month
  • Ibandronate 3 mg intravenously every 3 months
  • Zoledronic acid 5 mg intravenously once a year.

Moreover, less than 1% of an oral dose is absorbed by the gastrointestinal tract,49 whereas more than 50% of the dose of bisphosphonates given intravenously is bioavailable,50 which may account for the lower incidence of jaw ostenonecrosis with oral agents.

Osteonecrosis of the jaw can occur spontaneously but is more often associated with dental procedures that traumatize bone, such as tooth extraction.51 In a systematic review,45 patients with multiple myeloma and metastatic cancer to the bone who were receiving intravenous bisphosphonates accounted for 94% of published cases. Sixty percent of cases were preceded by dental surgical procedures, and in 39% of cases that occurred spontaneously the lesions were located on bony exostoses, a possible source of trauma. Of 63 cases reported by Ruggiero et al,47 56 patients were receiving intravenous bisphosphonates and 7 were receiving oral bisphosphonates. Older age (> 65 years), chronic systemic steroid use, periodontitis, and prolonged use of bisphosphonates have also been associated with a higher risk of osteonecrosis of the jaw.51

The risk of developing osteonecrosis of the jaw in people taking bisphosphonates in doses recommended by the US Food and Drug Administration for treating osteoporosis is very low (the incidence is calculated at 0.7 per 100,000 person-years of exposure to alendronate).51,52 In a 3-year prospective study in more than 7,000 women with post-menopausal osteoporosis, the incidence of osteonecrosis of the jaw was no different in those treated with zoledronic acid 5 mg intravenously than in those receiving placebo.53 In a randomized, placebo-controlled study of the effect of 2 years of alendronate treatment on alveolar bone loss involving 335 patients with periodontal disease, no cases of osteonecrosis of the jaw were reported.43

The American Dental Association (ADA) released a statement noting that osteonecrosis of the jaw can occur with or without bisphosphonate use.51 To date, a true cause-and-effect relationship between osteonecrosis of the jaw and bisphosphonate use has not been established. Further studies are needed to fully explore this relationship. Our group is currently exploring novel periodontal assessments comparing the oral health of postmenopausal women with osteoporosis who are on no bone therapy vs postmenopausal women with osteoporosis treated with bisphosphonates for 2 or more years.

While we await further studies exploring this relationship, clinicians in direct care of patients who are or will be taking bisphosphonates should carefully assess risk factors before starting treatment and during treatment. In 2007, the American Association of Oral and Maxillofacial Surgeons released a position paper on bisphosphonate-associated osteonecrosis of the jaw,52 listing potential risk factors (Table 1) for its development, as well as management strategies for patients treated with bisphosphonates. To prevent this possible complication, they recommended a thorough oral examination before treatment with an intravenous bisphosphonate, and that “any unsalvageable teeth should be removed, all invasive dental procedures should be completed, and optimal periodontal health should be achieved.”52 They also proposed that “discontinuation of oral bisphosphonate for a period of 3 months prior to and 3 months after elective invasive dental surgery may lower the risk.”52 This should, however, be done in consultation with the treating physician and the patient.

Discussion of treatment for bisphosphonate-associated osteonecrosis of the jaw is beyond the scope of this article.

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