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July 17, 2007

Is there an association between osteoporosis and oral bone health, and if so, what is its nature and what are the clinical implications? This compound question broadly addresses a theme that is raised in this issue of Grand Rounds in Oral-Systemic Medicine.^™ Osteoporosis is a systemic skeletal disease characterized by reduced bone strength and increased risk of low-trauma fracture. Periodontitis is a process characterized by alveolar bone loss and loss of soft tissue attachment to the tooth, leading to increased risk of tooth loosening and tooth loss. Osteoporosis and periodontitis share common risk factors that include advanced age, estrogen deficiency, cigarette smoking, glucocorticoid therapy, and anticonvulsant therapy. Both are silent diseases with serious clinical consequences. The “final endpoint” of fracture with osteoporosis and tooth loss with periodontitis is analogous in some ways to stroke in patients with hypertension and myocardial infarction in those with hypercholesterolemia. All of these underlying diseases are multifactorial in origin. The risk of their final endpoints can be reduced by appropriate medical interventions. It is plausible to hypothesize that osteoporosis, being a systemic disease, might have harmful effects on jaw bone, just as it does at other skeletal sites, and that this might be a contributing factor in the pathogenesis of periodontitis. It is also plausible to hypothesize that the inflammatory process initiated by bacterial infection and release of cytokines associated with periodontitis may have effects on bone both locally and systemically. There are other chronic inflammatory diseases that are associated with local and systemic skeletal effects. For example, rheumatoid arthritis (RA) is associated with focal bone erosions in areas of active arthritis as well as bone loss at skeletal sites that are remote from areas of active arthritis. Although the chronic inflammation of RA is autoimmune in origin, while the inflammation of periodontitis is because of bacterial infection, data¹ suggesting a relationship between these two disabling diseases support the concept of chronic inflammation having adverse skeletal effects.

Many studies have examined the relationship between osteoporosis and oral bone loss.² Most, but not all of these, have concluded that there is, or may be, a link between these disorders. Unfortunately, evaluation of the evidence is often confounded by small sample size, cross-sectional study design, inadequate control of variables, variable methods for assessing systemic bone mineral density (BMD) at different skeletal sites, and variable methods for measuring oral BMD. The “gold standard” method for diagnosing osteoporosis and monitoring changes in BMD over time is dual-energy x-ray absorptiometry (DXA) of the lumbar spine, total proximal femur, femoral neck, and sometimes the 33% (one-third) radius region of interest.³ Periodontal disease is typically assessed by methods that include visual inspection, probing to measure alveolar crestal height (ACH), and oral radiography to obtain an image of intact teeth and surrounding alveolar bone. There is no standard technology or region of the jaw for measuring oral BMD. Preliminary data suggest that slightly modified dental panoramic radiography could be used as a screening tool to identify patients at high risk for osteoporosis, possibly opening the door for dentists to play a role in improving patient awareness of non-dental skeletal disorders. Despite the recognized limitations of published clinical trials, the United States Surgeon General has stated in Bone Health and Osteoporosis, that oral bone loss and tooth loss are associated with osteoporosis, and that osteoporosis and osteopenia may have “an impact on the need for, and the outcomes from, a variety of periodontal and prosthetic procedures.”⁴ Clearly, however, well-designed long-term prospective clinical trials are needed to validate the relationship between periodontitis and systemic osteoporosis, and to enhance our understanding of the factors linking these two diseases.

Another aspect of the association between osteoporosis and oral bone health concerns the effects of treatment of one on the other. Particular attention has been focused on the effects, for better or for worse, of treatments for osteoporosis on bone in the jaw. Anti-resorptive (anti-catabolic) therapy for osteoporosis (e.g., estrogen, bisphosphonates) has been associated with improved ACH, increases in mandibular BMD, and tooth retention. There are limited preclinical data suggesting that anabolic therapy for osteoporosis with teriparatide (recombinant human parathyroid hormone 1-84) may also have potential benefits for oral bone health. Long-term follow-up of patients treated with alendronate, the bisphosphonate most commonly used to treat osteoporosis, suggests that it is safe and effective with continuous use for at least 10 years.⁵ High doses of injectable bisphosphonates given at frequent dosing intervals for the treatment of cancer or related conditions have been associated with osteonecrosis of the jaw (ONJ).⁶ While there have also been some reported cases of ONJ in patients treated for osteoporosis with lower doses of bisphosphonates, whether given orally or by injection, the risk appears to be extraordinarily low at about 0.7 per 100,000 patient-treatment-years.⁷ This is far less than the risk of a fragility fracture and less than other risks commonly faced in modern society, such as the risk of death by motor vehicle accident or by homicide.

Until more data are available to better define the relationships between osteoporosis and oral bone health, and until we have a better understanding of the global risks and benefits of therapeutic interventions for one on the other, we must continue to manage our patients with these common disorders. What do we do until the data arrive? Here are a few suggestions:

1. For all healthcare professionals, every patient encounter is an opportunity to improve skeletal and oral bone health by promoting healthy lifestyle measures and discouraging unhealthy behavior. Patients can be counseled on the importance of good nutrition; especially having adequate intake of calcium and vitamin D, the benefits of regular exercise, avoiding tobacco smoking or chewing, and limiting alcohol drinking. Regular medical and dental checkups according to standard guidelines should be recommended.
2. Dental healthcare professionals who care for patients with periodontitis, particularly when there is tooth loosening or tooth loss, can suggest that they may be at risk for osteoporosis, and encourage follow-up by a primary care provider. This may be sufficient to later initiate a risk factor assessment, modification of potentially reversible risk factors, and further diagnostic evaluation by DXA. Some of these patients may benefit from pharmacological intervention to reduce fracture risk.
3. Medical healthcare professionals managing patients with osteoporosis should advise vigilance at maintaining good oral hygiene and having routine dental care. Prior to starting a bisphosphonate for the treatment of osteoporosis, tell the patient there is a very small (but not zero) risk of ONJ. If a tooth extraction or invasive oral surgery is anticipated, it may be prudent to have the procedure completed, and assure bone healing, before starting the bisphosphonate. If the patient is already taking a bisphosphonate for the treatment of osteoporosis and a tooth extraction or invasive oral surgery is planned, consider stopping the bisphosphonate in advance of the procedure and restarting after bone healing has occurred.

Finally, there is a plea for collaboration and communication among dental and medical healthcare professionals. If we, as healthcare providers, have a better understanding of the diverse scientific literature, diagnostic tools, and therapeutic interventions that are used by colleagues in other patient care disciplines, then improved clinical outcomes for our patients are the likely result.

References

1. Mercado F, Marshall RI, Klestov AC, et al. Relationship between rheumatoid arthritis and periodontitis. J Periodontol. 2001;72:779-787.
2. Oh T, Bashutski J, Giannobile W. The interrelationship between osteoporosis and oral bone loss. Grand Rounds Oral-Sys Med. 2007;2:10-21.
3. Binkley N, Bilezikian JP, Kendler DL, et al. Official positions of the international society for clinical densitometry and executive summary of the 2005 position development conference. J Clin Densitom. 2006;9:4-14.
4. US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD, US Department of Health and Human Services, Office of the Surgeon General; 2004.
5. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189-1199.
6. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753-761.
7. American Dental Association Council on Scientific Affairs. Dental management of patients receiving oral bisphosphonate therapy: expert panel recommendations. J Am Dent Assoc. 2006;137:1144-1150.

   E. Michael Lewiecki, MD, FACP, New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM

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