Osteoporosis and periodontal disease: systemic influences
Osteoporosis is a global health concern; between 6% and 7% of people world-wide are affected by this disease of the skeletal system. The International Osteoporosis Federation reports that it affects an estimated 75 million people across Europe, the USA and Japan (EFFO and NOF, 1997). Around one in three women and one in seven men over the age of 50 will, at some stage, suffer a bone fracture as a result of osteoporosis.
It is further estimated that one in four Irish women and one in 20 Irish men will suffer a fracture due to osteoporosis by the age of 60. In 1996, 1,117 Irish women over the age of 55 were admitted into hospital with a diagnosis of osteoporosis. The World Health Organization (WHO) considers osteoporosis to be one of the most significant health problems.
The question of whether osteoporosis and alveolar bone loss have a causal relationship remains the subject of much research. Since alveolar bone loss is a prominent feature of periodontal disease, osteoporosis is thus suspected of being a contributing factor in the progress of periodontal destruction.
A possible correlation between general systemic osteoporosis and alveolar bone loss in periodontal disease pathogenesis has been studied since the early 1970s.
Osteoporosis and periodontal disease both have multi-factoral aetiologies and periodontal disease is known to exist in several forms. This makes it difficult to demonstrate a clear cut relationship between the two diseases.
The mechanism by which such an association could exist identifies the role of cytokines in the pathogenesis of both diseases (Loza J et al, 1996). Local stimulators of bone metabolism such as cytokines are particularly involved in the co-ordination of many events leading to the overall loss of bone seen in osteoporosis and periodontal disease.
Interleukin-1 (IL-1), tumour necrosis factor (TNF), interleukin-6 (IL-6) and prostoglandin E1 (PGE1) have been shown to regulate osteoclast generation (Nair SP et al, 1996). Their potential as mediators of post-menopausal osteoporosis was suggested by Ralston (1994), who found that IL-1a, IL-1b and IL-6 were present significantly more often in post-menopausal women with osteoporosis.
Particularly applicable to this work was the finding by Stashencko (1991), who showed a positive correlation between IL-1b levels in periodontal tissue and attachment loss in humans.
Katamanga (1989) also showed that IL-6 levels were higher in periodontally involved gingival tissue than in healthy tissue. This evidence supported the concept that the pathogenesis of osteoporosis may also be affected by increased production of local cytokines that uncouple bone remodelling, resulting in net bone loss. It was therefore suggested that increased cytokine levels were responsible for decreased bone mass and that osteoporosis can have an additive effect on the periodontal tissues, leading to greater attachment loss (Von Wowern N et al, 1994).
Bone mineral density
The relationship between skeletal loss of mineral density and increased periodontal bone loss has been researched for over 30 years, with much of the research reaching contradictory conclusions.
A number of studies have reported a significant relationship between systemic osteoporosis and loss of periodontal tissue. Von Wowern et al (1994) conducted a controlled study comparing 12 osteoporotic fracture women with 14 healthy women. They found there was a significantly greater loss of periodontal attachment in the osteoporotic group.
Similar findings were reported in a later cross-sectional study of the association between systemic bone mineral density (BMD) and periodontal status. Statistically negative correlations were found between BMD and tooth loss, and BMD and attachment loss, independent of plaque scores (Mohammed AR et al, 2003).
Krall et al (1996) concluded that increased systemic bone loss may be a risk factor for tooth loss by contributing to the resorption of alveolar bone.
Tezal et al (2000) conducted a study of known confounding factors. Clinical attachment loss consistently appeared to be related to bone mineral density at all sites in the skeleton. The results did not reach statistical significance, however the authors concluded that their findings suggested that skeletal BMD is related to interproximal alveolar bone loss and, to a lesser extent, to clinical attachment loss, implicating post-menopausal osteopaenia as a risk indicator for periodontal disease in post-menopausal women.
An earlier two-year longitudinal study conducted by Payne et al (1999) also found that osteoporotic women exhibited a higher frequency of loss of alveolar bone height compared to women with normal BMD.
In contrast, other authors have found no such association. Kribbs (1990) compared periodontal measurements in normal and osteoporotic women and found no differences in periodontal measurements in their molar teeth. Mandibular bone density was, however, significantly greater in the control group than the study group. There was also a greater percentage of edentulous subjects in the osteoporotic group, and in subjects who had natural teeth there was a significant degree of tooth loss in the osteoporotic group.
Elders et al (1992) reported no such relationship between periodontitis and systemic bone mass. They compared oral clinical findings to bone mineral content of the lumbar spine and the thickness of the middle three fingers of both hands. When no correlation was found, they suggested the relationship between periodontitis and systemic bone mass was not significant. What was not examined in this study was whether, in more severe manifestations of periodontitis, a relationship to osteoporosis does exist, and whether general skeletal bone mass has an effect on the severity and progression of pre-existing periodontitis.
In a later study, Weyant et al (1999) were still unable to provide an association between periodontal disease and systemic BMD.
Why do such disparities exist? If osteoporosis is a predisposing factor for periodontal disease, then a relationship between measures of systemic bone mineral density and periodontal destruction should be consistently demonstrated.
Differences between the studies and the interpretation of the results are complicated by the variety of methods used to assess osteoporosis and periodontitis. Currently there appears to be no standardised, precise method to measure overall bone density.
BMD is frequently used as a proxy measure and accounts for approximately 70% of bone strength (Kanis JA et al, 2002).
The WHO definition of osteoporosis is based on mean bone density for young white females. It is difficult to apply, therefore, to men, children and ethnic groups. Disparities also exist with regard to measurement and standardisation between instruments and choice of skeletal sites for measurement.
Many of the studies looking at a relationship between the two diseases are often hindered by small sample sizes, non-comparable study populations, different methods of assessing disease and limited control of confounding factors.
Since osteoporosis and periodontal disease progress in a chronic pattern, the use of cross-sectional studies is limited, since little information is available about the pattern of the disease during a short period of study.
Comparing BMD with tooth loss also has its limitations, as it is impossible to determine the cause of a lost tooth from a single examination. Teeth may be lost for many reasons other than decreased bone support.
Osteoporosis can be further characterised as either primary or secondary. Primary osteoporosis can occur in both sexes at all ages, but most commonly follows menopause in women and occurs later in life in men. In contrast, secondary osteoporosis is as a result of medications (such as glucocorticoids) or other conditions (such as renal failure, organ transplant and hyperthyroidism).
Add to this other confounding factors such as age, gender, smoking, nutrition, hormone balance, plaque control and host susceptibility to plaque, the ability to compare research matched by methods and design becomes increasingly more difficult.
The most common cause of osteoporosis in women is the oestrogen deficiency that usually accompanies menopause.
Menopause usually begins at approximately 45 to 55 years of age, unless accelerated by hysterectomy or ovariectomy. At this stage of life there is a dramatic decrease in oestrogen and progesterone production.
Whereas the pre-menopausal woman has cycling plasma levels of oestrodiol and progesterone of 50-500pg/ml and 0.5- 20ng/ml respectively, the post-menopausal woman has non-cycling, circulating levels of 5-25pg/ml and 0.5ng/ml respectively.
Clinical conditions causing low oestrogen environments in post-menopausal women allow T-cell and B-cell abnormalities, increased local production of the bone-active cytokines (i.e. IL-1, IL-6, IL-8 and tumour necrosis factor-alpha) and a rise in prostaglandin E2 (PGE2), which may result in the progression of periodontitis.
Oestrogen and bone loss
The function of oestrogen in maintaining bone mass was established over 60 years ago by Dr Fuller Albright (1940), who first showed that post-menopausal women had an accelerated rate of bone loss.
Several theories exist as to the mechanism by which oestrogen blocks bone resorption. Oestrogen deficiency has been shown to affect serum calcium (Ca+) homeostasis. With the development of oestrogen deficiency, increased bone resorption occurs due to an increased responsiveness of bone to parathyroid hormone (PTH). Evidence of greater bone turnover includes an increase in serum and urine calcium, as well as a rise in markers of bone turnover such as serum alkaline phosphatase, osteocalcin and urinary hydroxyproline.
The transient rise in serum calcium, from increased release of bone calcium into the extracellular pool, decreases PTH secretion. Both decreased serum PTH and the resultant increase in serum phosphate decrease the rate of 1,25-dihydroxyvitamin D production and thus decrease intestinal Ca+ absorption. Decreased serum PTH also decreases tubular Ca+ reabsorption. Both decreased Ca+ absorption and increased renal calcium loss normalise the serum Ca+ concentration. Thus the serum Ca+ concentration is maintained, more by bone loss, however, than by absorbed dietary Ca+. Studies have shown that oestrogen therapy reverses this sequence (Lindsay R, Cosman F, 1990).
In addition, oestrogen has been shown to increase the secretion of insulin-like growth factor 1 and transform growth factor b in sufficient amounts, which could inhibit osteoclast recruitment or function (Girasole G et al, 1990). In addition, oestrogen appears to inhibit the release of IL-1 and IL-6 from mononuclear cells (Girasole G et al, 1990; Pacifici R et al, 1988).
Manolaglas et al (1992) also reported that oestrogen deficiency stimulates production of IL-6, which causes growth of osteoclasts and bone resorption. Oestrogen deficiency in rats is also associated with production of PGE2 in bone, stimulating bone resorption. Oestrogen lowers PGE2 production in bone and may therefore reduce bone resorption (Feyen JHM, Raisz LG, 1987).
Alveolar bone loss
A number of studies have linked oestrogen deficiency with periodontal breakdown and tooth loss. This has prompted the conclusion that oestrogen deficiency can be considered as a systemic factor that exacerbates the onset and progression of periodontal disease (Jonson RB et al, 2002).
Oestrogen deficiency increases the rate of breakdown of the gingival tissues by stimulating synthesis of metalloproteinases and several cytokines implicated in bone resorption (Streckfus CF et al, 1997). Oestrogen deficiency has also been shown to increase IL-6 concentrations in gingival tissue, stimulating osteoclast activity (Jonson RB et al, 2002).
A study of pre- and post-menopausal women reported a significant correlation between alveolar bone density, skeletal BMD and elevated salivary concentrations of IL-6 in post-menopausal women (Reinhart FA et al, 1999).
Payne et al (1997) were able to show a positive effect of 17beta estradiol (E2) on alveolar bone density. Overall, inter-proximal changes revealed E2 sufficient women exhibiting a net gain of alveolar bone density and E2 deficient women a net loss. This was followed by a three-year, double-blind, randomised, placebo-controlled study of 135 post-menopausal women who had no previous history of periodontal disease (Civitelli R et al, 2002). The researchers suggested that the positive effects of hormone/oestrogen replacement therapy (H/ERT) on post-cranial bone density are accompanied by similar positive effects on alveolar bone mass.
Both groups also took daily calcium and vitamin D supplements. At the end of the study, the researchers found that the women who received H/ERT in addition to the supplemental micronutrients had a ‘significantly’ greater increase in alveolar bone mass (1.84%) compared to the women who took the placebo (0.95%).
Both periodontal disease and osteoporosis have a number of risk factors in common. These include genetic predisposition and increased age, as well as environmental and lifestyle factors such as smoking and caffeine, cola and alcohol intake.
Bone modelling and skeletal consolidation result from a sequence of nutritional and hormonal interactions. Because nutrition is a modifiable pathogenic factor in osteoporosis that also appears to have important oral health implications, it is a topic that deserves some attention.
Given the physiology of alveolar bone, with osteoblast and osteoclast activity, and it being supported by compact and cancellous bone, it is not unreasonable to extrapolate risk factors in systemic bone density to alveolar bone. Nutrition is an important factor in systemic bone health and may also have implications in the rate at which alveolar bone is lost.
A number of more recent studies have suggested that alveolar bone mass is sensitive to nutrient intake. Nishida et al (2000a) suggest that low dietary calcium is linked to more severe cases of periodontal disease. Other research highlights vitamin C (Amarasena N et al, 2005; Nishida M et al, 2000b) and vitamin D (Dietrich T et al, 2005) as being associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss (Krall EA et al, 2001).
To date, the majority of studies on the relationship between periodontal disease and osteoporosis have been hindered by the vast number of factors already referred to in this article.
In order to clarify the association between periodontal disease and osteoporosis, more large scale longitudinal studies with further analysis of possible confounding factors in larger cohorts of women are required. Measurement sites and methods need to be standardised to ensure reliable and comparable data are obtained.
In the meantime, however, adequate evidence exists as to the multiple risk factors shared by these two diseases. Although the mechanism is still not understood, studies to date indicate a possible correlation between systemic and oral bone loss. If good oral hygiene is combined with regular periodontal screening and good nutrition, the effects of osteoporosis on the oral tissues can be minimised.