Osteoporosis and periodontal disease affect a significant number of the population worldwide. Both conditions are bone resorptive diseases, but have different aetiologies. Osteoporosis is well known for causing systemic bone mineral density reduction and increasing the risk of skeletal bone fracture if not treated appropriately. Periodontal disease involves alveolar bone resorption in both upper and lower dental arches of the oral cavity and may lead to loss of teeth. The following paper explores the pathogenesis and treatment of osteoporosis, and its association with periodontal disease.
Introduction
Osteoporosis is a skeletal condition involving reduced systemic bone mass with changed trabecular bone architecture and increased risk of bone fractures, such as hip fractures (Yu, 2004). It is defined by the World Health Organisation (WHO) as bone mass 2.5 standard deviations or more below the mean, while osteopenia (a similar but less significant loss of bone mass) is defined as bone mineral density between 1 and 2.5 standard deviations below the mean (Yu, 2004; Jeffcoat, 2005; Geurs, 2007). It is estimated that five percent of the Australian population suffer from osteoporosis, with more than 50 percent of females older than 60 years of age affected by the condition (Cheng et al, 2009). In Australia, one in two women and one in three men over the age of 60 will have some form of bone fracture related to osteoporosis (Osteoporosis Australia, 2007). In 2006-07 alone, there were over 16,500 hip fractures affecting Australians of 40 years and over with osteoporosis (Australian Institute of Health and Welfare, 2010).
An increasing number of studies suggest an association between osteoporosis and periodontal disease. Periodontal disease is destruction of the periodontal tissues via inflammation produced by bacterial infection. The effects of periodontal inflammation include alveolar bone resorption, dental attachment loss, and thus an increased risk of tooth loss (Inagaki et al, 2005). It can develop chronically or as an aggressive condition, and affects the majority of the population, with 10-15% of the population suffering from aggressive periodontitis (Wolf & Hassel, 2006). While there may be some common factors involved in the development of osteoporosis and periodontal disease, there is yet to be a clear cause-and-effect association between the two conditions. This lack of evidence to prove or disprove a cause-and-effect relationship between osteoporosis and periodontitis is mainly due to a lack of well-controlled longitudinal prospective studies involving large sample sizes (Stabholz et al, 2010).
The Pathogenesis of Osteoporosis
Bone Remodelling
Bones are dynamic structures. They undergo phases of resorption and new bone formation in a process known as bone remodelling (Lerner, 2006b). This process is essential as it allows bone to better withstand the functional loads placed on it, and therefore allow it to act as a better supporting frame for bodily tissues (Lerner, 2006a). Ideally, bone resorption and bone deposition processes are balanced, maintaining a systemic bone homeostasis (Lerner, 2006a & b).
Figure-1 describes the process by which bone is remodelled and the timeframe in which it usually takes place. Osteoblasts (bone matrix-producing cells) and osteoclasts (bone-degrading cells) are the main cells involved in the bone remodelling process.
Figure-1: Remodelling Units
Source: Lerner, 2006a
From Lerner, 2006a
Risk Factors for Osteoporosis
The risk factors for osteoporosis can be categorised into modifiable (e.g. smoking, lack of exercise) and non-modifiable risk factors (e.g. gender, early menopause) (Jeffcoat, 2005; Geurs, 2007). Table-1 provides a concise listing of these risk factors and their ability to be modified.
Table-1: Risk Factors for Osteoporosis
Risk Factor
Modifiable
How Modifiable
Gender
No
Age
No
Early menopause
No
Low bone mass
Yes
Treatment of osteoporosis or osteopenia
Race
No
Lack of calcium
Yes
Diet high in calcium or vitamin D
Lack of exercise
Yes
Weight bearing exercise
Smoking
Yes
Smoking cessation
Alcohol
Yes
Decreased alcohol consumption
Heredity
No
Diseases
To some extent
Treatment
Medications (chronic glucocorticoid use)
To some extent
Alter treatment if feasible
Propensity to falling
To some extent
Adapted from Jeffcoat, 2005 & Geurs, 2007Physical therapy, neurological treatment if possible
The Post-Menopausal Patient
One of the most important factors predisposing individuals to osteoporosis is menopause onset, and this can be seen in the prevalence of osteoporosis in post-menopausal women (Jeffcoat, 2005). Hormones, such as oestrogen, play an important role in the development of osteoporosis in post-menopausal women.
Immediately after menopause oestrogen levels drop (Jeffcoat, 2005). Oestrogen normally inhibits the expression of pro-inflammatoy cytokines from cells that are situated near osteoclasts, such as stromal and inflammatory cells (Mundy, 2007). While this acts to protect bone from undergoing increased turnover in unaffected individuals, in post-menopausal patients this protection is lost with the reduction in oestrogen production. Hence, there is greater expression of pro-inflammatory cytokines, which can activate osteoclasts and induce bone resorption (Mundy, 2007). According to Lerner (2006b), there is both increased bone deposition and increased bone resorption when there is reduced oestrogen production. However, the bone resorptive process occurs at a greater rate than the bone forming process, resulting in net bone loss (Lerner, 2006b).
The Non-Post-Menopausal Patient
In men, the main causes of osteoporosis are chronic glucocorticoid medication use, reduced testosterone levels (hypogonadism) and smoking (NIAMS, 2010). Other causes of osteoporosis in men, and also in non-post-menopausal women, include excessive consumption of alcohol, gastrointestinal disease, hypercalciuria and immobility (NIAMS, 2010).
Calcium and Vitamin D
Calcium plays an important role in maintaining healthy bones. According to Lanou et al (2005), bone-forming osteoblasts use dietary calcium and other minerals, such as phosphorus, to create bone matrix which mineralises to form hydroxyapatite crystals. Therefore, it can be concluded that a critical concentration of calcium and other minerals must be present for osteoblasts to lay down bone matrix. In addition, vitamin D helps osteoblasts make new bone indirectly by enhancing the body's absorption of dietary calcium in the intestine (Holick, 2004).
Glucocorticoid medications are commonly used in treating asthma and rheumatic fever. The side effects of chronic glucocorticoid medication use include muscle weakness and decreased intestinal absorption of calcium (NIAMS, 2010).
Smoking: it it ture that tobacco, nicotine and other toxic chemicals from smoking can inhibit absorption of calcium and later affect bone health as explained before.
Testosterone and Other Hormones
Hypogonadism is characterized by low levels of sex hormones and according to studies, decreased level of male sex hormones may cause osteoporosis. Although it is normal that the testosterone level will decrease with age, to maintain homeostasis, it should decrease gradually and slowly. However, glucocorticoid medication, prostate cancer treatment and other factors can result in dramatic reduction of male sex hormone levels. In addition, androgens can pose direct effect on bone tissue by regulating proliferation, differentiation, mineralization and gene expression of osteoblastic lineage cells. Therefore, it is true that testosterone might be able to stimulate bone formation and if there is decrease in testosterone or androgen in men, it will increase the risk of developing osteoporosis later.
The Association between Osteoporosis and Periodontal Disease
Several of the pro-inflammatory cytokines released in osteoporosis are also released in periodontal disease, despite the two conditions developing via inherently different processes (Lerner, 2006a & b). These pro-inflammatory cytokines include interleukin-1β, tumour necrosis factor-α and interleukin-6 (Lerner, 2006a & b).
There are two suggested mechanisms by which osteoporosis and periodontal disease might be associated in post-menopausal women: (1) that osteoporotic jawbones with the addition of periodontal disease will increase the rate at which bone is lost; and (2) that oestrogen inhibits bone-resorbing cytokines and its deficiency produces an increased inflammatory response, and thus, increased periodontal destruction (Lerner, 2006b). In addition, the fact that several of the risk factors for osteoporosis are also risk factors for periodontal disease presents another possible association between the two pathological conditions.
Management and Treatment of Osteoporosis
Diagnosis of Osteoporosis
The medical history of a patient can be useful in screening for osteoporosis (Geurs, 2007). Particular consideration should be given to level of physical activity and fitness, pre-existing and chronic conditions, use of medications over a long period of time, and a history of bone fractures (Geurs, 2007). A patient with long-term use of glucocorticoids and a high propensity to falling and fracturing bones, for example, would indicate to the clinician that osteopenia or osteoporosis may be present in the individual.
However, history alone is insufficient in terms of diagnosis. Therefore, supplemental examinations and tests, such as physical examinations and X- rays, are essential in aiding diagnosis (Geurs, 2007). Dual-energy X-ray absorptiometry and quantitative computed tomography are known as the most accurate and reliable techniques for screening for osteoporosis (Geurs, 2007). Conventional radiographs are not sensitive enough to detect osteoporosis unless more than 50% of bone has been lost (Geurs, 2007). The determined bone mineral density given by these diagnostic tests enables classification of patients as normal, osteopenic or osteoporotic (Geurs, 2007). This classification is important as it enables the clinician to prescribe the most appropriate treatment plan for the patient.
In addition, lab tests play an important role in screening for related causative factors, and excluding secondary causes of osteoporosis in the patient (Geurs, 2007).
Prevention of Osteoporosis
Since both calcium and vitamin D are important for maintaining systemic bone levels, it is recommended that calcium and vitamin D supplements are used to prevent the onset of osteopenia or osteoporosis. The aim of calcium and vitamin D supplementation is to help control parathyroid hormone levels, which normally increase with age. Parathyroid hormone has a role in elevating bone resorptive processes (Beatrice & Cesar, 2008).
One way of avoiding osteoporosis is increasing the peak bone mass reached by the age of (25-30 years) so that bone loss later on during life will not be as detrimental to the affected individual. By performing weight-bearing exercises, patients may find it helpful in increasing their peak bone weight, enabling them to maintain it for a longer period of time (Beatrice & Cesar, 2008).
As postmenopausal women are at increased risk of developing osteoporosis, they are advised to have annual check-ups with their medical practitioners. Should a patient have a history of past hip or vertebral fractures, consideration should be given regarding placing the patient on osteoporosis treatment (Geurs, 2007). For postmenopausal women who are younger than 65 years old with risk factors other than menopause, a bone mineral density test should be undertaken to assess their risk of developing osteopenia or osteoporosis. For those beyond the age of 65, testing should be performed regardless of any other related risk factors (Geurs, 2007).
Patients at greater risk of developing osteoporosis are also recommended to reduce and cease modifiable risk factors, with regular monitoring of these risk factors (Geurs, 2007)
Treatment Options for Osteoporosis
The main aims of treatment are to decrease modifiable risk factors, e.g. smoking reduction or cessation and to introduce protective factors, such as calcium and vitamin D supplements and weight bearing exercises. For non-modifiable risk factors, hormone replacement therapy and drug therapy may be useful.
Hormone replacement therapy
Oestrogen deficiency in early postmenopausal woman leads to rapid bone loss. Hormone replacement therapy works by blocking osteoclast synthesis and function. It also increases the lifespan of osteoblasts and osteocytes (Geurs, 2007). This type of therapy prevents both trabecular and cortical bone loss. Studies have shown evidence of similar degrees of increasing bone density regardless of the dosages used in this treatment modality. The major potential side effects of oestrogen replacement therapy are increased risk of developing breast cancer and cardiovascular conditions (Geurs, 2007).
Selective oestrogen receptor modulators
This treatment works by decreasing bone turnover via similar mechanisms as estrogen but minimizes the side effects (Geurs, 2007). It is effective in preventing bone fractures except for non-vertebral fractures. Side effects of this treatment are hot flashes and leg cramps. Raloxifene is an example that has shown an ability to reduce breast cancer risk, but increase risk of developing deep vein thrombosis (Geurs, 2007).
Bisphosphonates
Bisphosphonates works by binding to bone mineral so it can be taken up by osteoclasts (still need to rephrase). The osteoclasts are deactivated and cell death is accelerated, hence suppressing bone resorption. It works to improve bone mass and bone strength, and to also decrease incidence of bone fractures. Long term use of bisphosphonates can be safe without adverse effects. Even with discontinuation of bisphosphonate therapy after long-term use, minimal bone loss has been found (Geurs, 2007). However, there is a severe oral concern in using intravenous biphosphonates in that it has the potential to initiate osteonecrosis of the jaw by producing ischaemic changes in the maxilla and mandible (Geurs, 2007; Cheng et al, 2005). Patients with long term use of bisphosphonates may thus have compromised blood supply to their maxilla and mandible (Cheng et al, 2005). Clinical manifestations of osteonecrosis are altered health in the periodontal tissues, such as unexplained soft tissue infection, loosening of teeth and impacted healing of mucosal ulcers (Geurs, 2007). The most common finding in people being treated with intravenous bisphosphates is periodontitis, with more than 80% of cases developing periodontitis (Geurs, 2007).
Calcitonin
Calcitonin works by inhibiting osteoclasts function. Treatment options available are nasal and subcutaneous calcitonin (Geurs, 2007).
Treatment Options for Periodontitis
For patients who have moderate chronic generalized periodontitis, professional scaling and cleaning by sextant should be performed as an initial therapy. Then, review of how the soft tissue and bone respond to treatment is important and essential. Usually, for those patients, 2-3 recall sessions should be arranged for maintenance purpose every year.
On the other hand, for patient who has sever and aggressive forms of periodontitis, apart from professional cleaning, a combination of periodontal surgery and antibiotics course maybe required to achieve better outcomes. If after the removal of deposits there left a deep pocket, then gingivectomy is often applied to eliminate the pocket (Ardakani & Mirmohamadi, 2009). Common antibiotics used to treat perio patient include: Amoxil (penicillin-based), tetracyclines, flagyl (metronidazole), and last but not least Azithromycin. In addition, increased number of recall sessions, usually 3-6 times every year aids to monitor the progression of diseases.
Unfortunately, for downhill patient, those who do not respond favorably to treatment done in the past, palliative therapy is probably the only option which mainly aims to deal with any coming up symptoms.
Clinical relevance
Dentists as Pre-screeners
The role of dentist as a pre-screener for patient who might have osteopenia and osteoporosis is important. Being familiar with the risk factors and clinical symptoms would allow dentist to differentiate patient who are at high risk to develop the osteoporosis and make early diagnosis and treatment possible. This can significantly decrease individual's financial expenses, improve prognosis and avoids severe symptoms. Dentists are advised to counsel for further evaluations of patients' bone status. During dental treatment, obtaining information from radiographs such as alveolar trabecular pattern and mandibular bone mass can be used to evaluate bone mineral density (Geurs, 2007; Edwards & Migliorati, 2008).
Even though dentists can be the early detectors, they are not trained to diagnosis osteoporosis and simple diagnosing condition from dental radiographs are inappropriate and inaccurate (Ardakani & Mirmohamadi, 2009)
Treatment of Periodontitis in Patients with Osteoporosis
Osteoporosis is a risk factor that modifies the onset and progression of periodontitis (Pejcic et al, 2005). It also shares many common risk factors with advanced periodontitis (Geurs, 2007). Studies have shown greater incidence of tooth loss with patients suffering from osteoporosis (Pejcic et al, 2005). Pro-inflammatory cytokines and prostaglandins are found in both diseases and make significant contributions to the pathogenesis of each disease (Pejcic et al, 2005). The two disease processes both involve increased levels of pro-inflammatory factors and new research may be able to reveal that changed appearance of pro-inflammatory cytokines in the periodontitis by bacteria could also be the source of osteoporosis (Pejcic et al, 2005). If changes are observed in the alveolar bone in osteoporotic patients, monitor of the periodontal maintenance is essential. In addition, for patients who are on biphosphonate therapy, there is suggestion that discontinuation of the drug for sometime before any dental interventions is an effective protocol, but there has not been any scientific evidence supporting this point (Edwards & Migliorati, 2008). It was suggested by the same authors that dentists having discussion with medical doctors in regards to individual patient's situation with whether or not to discontinue the biphosphonate is the best way to manage.
Discussion
During the research, we have found deficiencies and lacking of information in the current papers on the links between the osteoporosis and periodontitis. For example, studies that conducted within Australia on epidemiology of osteoporosis are mainly focused on the population over age 60 as they have much higher incidence of osteoporosis. For the population under 60, there are hardly any significant data or researches conducted. There are some national health organisations we come cross that do not provide valid information on a whole population scheme, which somehow can be very misleading. When talking about the relationship between the two diseases, majority of studies have covered that they share common risk factors, but no studies have covered why they have so many common risk factors and how these factors affect each diseases thoroughly. There are some new areas researchers are conducting studies in, such as they have found some common pro-inflammatory cytokines in both diseases, however there are not much in-depth information on mechanisms and significances of the research.
There have been contraindications and inconsistence in most published studies on osteoporosis and periodontitis. As mentioned in Ardakani & Mirmohamadi 2009, in some human studies showed that metacarpal bone geometry has association with periodontitis However, in the follow-ups, no correlations were found with metacarpal bone index and alveolar ridge resorption.
There is lack of evidence that systemic bone loss will have a direct effect on the periodontal health, as clinically the measurements of number of teeth, pocket depth and alveolar bone loss are not significant different to people without osteoporosis. Nevertheless, there are some studies showed that with oestrogen replacement therapy in post-menopausal women, there is less bone loss, but the results are not clinically significant either.
In most studies, the study groups are selected on strong bias, e.g. post-menopausal women, women who are very health conscious, and groups that can be easily accessed, hence may not be representative. In a similar way, sample sizes are normally small, making them not representative as the rest of the population barely being studied. In different studies, the measurements for oral bone quantity and quality can be different with different instruments used, different ways to calculate and different references they use. With the fact that the density of oral bone varies in different places in nature, most studies did not include this factor and hence the results are accurate for conclusion. The most important deficiency in majority of studies is the lack of control of other factors that may have effects on the bone.
Summary
Osteoporosis and periodontitis are found in population across all nations and races. Osteoporosis is associated with loss of bone mineral density which weakens bones systemically and may later result in bone fracture. On the other hand, periodontitis is characterized by resorption of alveolar bone which later leads to loss of teeth. It had long been stated that osteoporosis may contribute to the aetiology of periodontitis. Unfortunately, there is a lack of evidence shows that a conclusive relationship does exist between osteoporosis and periodontitis. However, a lot of studies prove that those two diseases could be interrelated as both of them share some risk factors, such as smoking. Moreover, both diseases affect bones. If a link between those two has been proven do exist, this will pose a significant implications for periodontal treatment and prevention especially for postmenopausal women.
Further research should focus more on whether osteoporosis is a risk factor for periodontal diseases, and if it is, what is the mechanism. In addition, longitudinal studies with large sample sizes are required in order to obtain more accurate results. Last but not least, clinical trials should be carried out examining the effectiveness of incorporating hormone therapy into periodontal treatment for postmenopausal women.
References
Ardakani FE & Mirmohamadi S, 2009. Osteoporosis and oral bone resorption: a review, Journal of Maxillofacial and Oral Surgery, 8(2):121-126
Australian Institute of Health and Welfare, 2010. The problem of osteoporotic hip fracture in Australia, Australian Government, Bulletin 76, accessed online 7/9/10 at <http://www.aihw.gov.au/publications/aus/bulletin76/10695.pdf>
Cheng A, Daly CG, Logan RM, Stein B & Goss AN, 2009. Alveolar bone and bisphosphonates, Australian Dental Journal, 54(1 Suppl): S51-S61
Cheng A, Mavrokokki A, Carter G, Stein B, Fazzalari NL, Wilson DF & Goss AN, 2005. The dental implications of bisphosphonates and bone disease, Australian Dental Journal 50 (4 Suppl 2): S4-13
Beatrice & Cesar
Edwards BJ & Migliorati CA 2008. Osteoporosis and its implications for dental patients, Journal of the American Dental Association, 139(5): 545-52
Geurs NC, 2007. Osteoporosis and periodontal disease, Periodontology 2000, 44: 29-43
Holick MF, 2004. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis, American Journal of Clinical Nutrition, 79(3): 362-371
Inagaki K, Kurosu Y, Yoshinari N, Noguchi T, Krall EA & Garcia RI, 2005. Efficacy of periodontal disease and tooth loss to screen for low bone mineral density in Japanese women, Calcified Tissue International, 77(1): 9-14
Jeffcoat M, 2005. The association between osteoporosis and oral bone loss, Journal of Periodontology, 76: 2125-2132
Koduganti RR, Gorthi C, Reddy V & Sandeep N, 2009. Osteoporosis: "a risk factor for periodontitis", Journal of Indian Society of Periodontology, 13(2): 90-6
Lanou AJ, Berkow SE & Barnard ND, 2005. Calcium, dairy products, and bone health in children and young adults: a reevaluation of the evidence, Pediatrics, 115(3): 736-743
Lerner UH, 2006a, Bone remodeling in post-menopausal osteoporosis, Journal of Dental Research, 85(7): 584-95
Lerner UH, 2006b. Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis, Journal of Dental Research, 85(7): 596-607
Mundy GR, 2007. Osteoporosis and inflammation, Nutrition Reviews, 65(12): S147-S151
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 2010. Osteoporosis in men, National Institutes of Health, accessed online 10/9/10 at <http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/men.asp>
Osteoporosis Australia, 2007. What is Osteoporosis? accessed online 7/9/10 at <http://www.osteoporosis.org.au/osteo_osteoporosis.php>
Pejcic A, Kojovic D, Grigorov I & Stamenkovic B, 2005. Periodontitis and osteoporosis, Medicine and Biology, 12(2): 100-103
Stabholz A, Soskolne WA & Shapira L, 2010. Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis, Periodontology 2000, 53: 138-153
Wolf HF & Hassel TM, 2006. Color Atlas of Dental Hygiene: Periodontology, Thieme: Germany
Yu LL, 2004. Osteoporosis and periodontal disease, Journal of the Chinese Medical Association, 67:387-388
