CLIMACTERIC 2014;17:1–5
Association between periodontal changes and osteoporosis in postmenopausal women F. M. B. G. Pereira, V. P. Rodrigues, A. E. F. de Oliveira, L. M. O. Brito* and F. F. Lopes Postgraduate Dentistry Program, Federal University of Maranhão, São Luís, Maranhão; *Department of Medicine III, Federal University of Maranhão, São Luís, Maranhão, Brazil Key words: OSTEOPOROSIS, OSTEOPENIA, BONE DENSITY, POSTMENOPAUSAL, PERIODONTAL DISEASES
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ABSTRACT Objective To investigate the possible association between periodontal changes and osteoporosis in postmenopausal women through a longitudinal study. Methods This longitudinal study included 33 patients. The participants were divided into three groups according to the bone mineral density assessed in the lumbar region: normal bone (G1, n 15), osteopenia (G2, n 12) and osteoporosis (G3, n 6). Periodontal evaluation included clinical attachment level, probing depth, gingival bleeding index and visible plaque index, evaluated by two examiners blinded to systemic bone condition. The statistical process included the t-test for paired samples, with a significance level of 5% to check for changes in periodontal parameters considered at initial and final systemic bone density. Results The results showed that, after follow-up, there was a significant increase in gingival bleeding index in the group of women who had normal initial bone condition and progressed to osteopenia (after 3 years, 59.89%, p 0.010) and osteoporosis (after 3 years, 74.37%, p 0.035). In addition, the group diagnosed with osteopenia at baseline who progressed to osteoporosis after 3 years also showed a significant increase in gingival bleeding index (p 0.001). Conclusions The findings suggest that periodontal changes can be associated with osteoporosis in postmenopausal women.
INTRODUCTION Periodontal disease is characterized as an immuno-inflammatory process triggered by the accumulation of biofilm on the outer surface of the tooth, which may eventually lead to destruction of periodontal ligament and alveolar bone1. Despite the dependence on primary bacterial etiologic factors, various behavioral factors, metabolic, hormonal and genetic, may modify the host response to biofilm, making it more susceptible to the development and progression of periodontitis2. Recent systematic reviews and meta-analyses of epidemiological studies suggest possible associations between periodontal disease and several systemic conditions: rheumatoid arthritis3, metabolic syndrome4, adverse pregnancy outcomes5, chronic kidney disease6, atherosclerosis7, and among them, osteoporosis8. The multifactorial nature of periodontal disease suggests that osteoporosis can act as an additional
predisposing factor, since the systemic factors responsible for osteoporosis may interact with local factors to increase the pattern of alveolar bone loss9. Data on the prevalence of osteoporosis are scarce and discontinuous, but it is estimated that approximately 10 million people over the age of 50 have osteoporosis10. This injury is correlated with menopause and decreased estradiol levels, as well as the main circulating estrogen. In this group of women, a cortical bone loss of 2–3% and a trabecular bone loss of 4–8% per year can be observed, leading to increased risk of fractures, especially in the hip and forearm11. The biological plausibility of the association between osteoporosis and periodontal disease may be related to the presence of several common risk factors such as tobacco use, poor nutritional status, advanced age, therapy with glucocorticoids, and immune disorders12. Although they have different primary etiologies, both diseases show increased produc-
Correspondence: Professor Dra F. F. Lopes, Universidade Federal do Maranhão, Programa de Pós-Graduação em Odontologia, Avenida dos Portugueses, s/n, Campus Universit ário do Bacanga, CEP: 65.085-580, São Luís, Maranhão, Brazil; E-mail: [email protected] ORIGINAL ARTICLE © 2014 International Menopause Society DOI: 10.3109/13697137.2014.966239
Received 07-07-2014 Revised 12-09-2014 Accepted 12-09-2014
Periodontal changes and osteoporosis
Climacteric Downloaded from informahealthcare.com by Korea University on 12/30/14 For personal use only.
tion of cytokines that stimulate osteoclast activity13. Besides that, estrogen receptors are expressed in bone and immune cells, and thus it has been suggested that changes in tissue levels of estrogen might also influence bone metabolism in periodontal sites with inflammatory processes, since the periodontal ligament cells express specific membrane receptors for estrogens14. Based on studies that have addressed the association between periodontal disease and osteoporosis which have found conflicting results15–20, and especially the lack of studies of longitudinal design, which may further elucidate the interaction between these two diseases, the present study investigates the possible association between periodontal changes and osteoporosis in postmenopausal women with a follow-up of 3 years.
METHODS This longitudinal, observational study was designed to determine the influence of systemic bone status on the periodontal status of postmenopausal women. The study group was composed of women aged 45–77 years who were recruited at Materno Infantil University Hospital (HUMI), of the Federal University of Maranhão (UFMA), located in São Luís, Maranhão. The inclusion criterion adopted was confirmation that the menstrual cycle had ceased for over 1 year; the exclusion criteria were the condition of less than six teeth, submission to periodontal treatment in the last 6 months, use of hormone replacement therapy (HRT), smoking history and diabetes mellitus. After all exclusions, the initial population consisted of 99 postmenopausal women. All these patients signed an informed consent form to participate in the study, the protocol for which was approved by the Research Ethics Committee of UFMA’s Presidente Dutra University Hospital (Notion n°. 172/08). The variables collected included data regarding systemic bone status and evaluation of the periodontal status of women in postmenopause. Participants were divided into three groups according to the classification of bone mass. The diagnosis
Figure 1
2
Pereira et al. of bone mineral density (BMD) was performed by bone densitometry using dual-energy X-ray absorptiometry (Lunar, USA) in the patient’s lumbar area (L2–L4 vertebrae). According to the World Health Organization criteria21, BMD variation difference was measured, in relation to that expected for healthy young women. After this procedure, three groups were formed: Group 1 normal bone (T-score 1), Group 2 osteopenia (T-scores between 1 and 2.5), and Group 3 osteoporosis (T-score 2.5). Two examiners performed the periodontal evaluation (κ 0.81). They were trained and blinded to the systemic bone status condition of patients. A clinical mirror and millimetered periodontal probe were used (Williams, Hu-Friedy, Chicago, IL, USA). The gingival bleeding index (GBI) and visible plaque index (VPI) were recorded in similar methodology as used by Habashneh and colleagues22, in which the measurements were obtained from four sites on each tooth (mesial, distal, buccal and lingual). Furthermore, the loss of support periodontal tissue was assessed by measurements of clinical probing depth (PD) and clinical attachment level (CAL), which were obtained from six sites on each tooth (mesiobuccal, mid-buccal, disto-buccal, mesio-lingual, mid-lingual and disto-lingual). Measurements were obtained from all teeth, except the third molars. The PD was defined as the distance from the gingival margin to the bottom of the periodontal pocket or gingival sulcus and the CAL was the distance from the cement–enamel junction to the bottom of the periodontal pocket or gingival sulcus, both measured in millimeters. Among the 99 women in the initial sample, only 33 women returned for reassessment after 3 years, and these made up the final sample for this study (Figure 1). The reasons for not returning for the follow-up (67%) were: change of address, submission to periodontal treatment in the last 6 months, diagnosis of diabetes mellitus, use of HRT and refusal to participate. The SPSS statistical program (version 17.0) was used to analyze the data. Initially, a descriptive analyses of the data were performed by averaging. The Shapiro–Wilk test was used to assess the normality of data distribution. The t-test for paired samples was used to determine statistical differences
Flowchart of monitoring and reassessment steps
Climacteric
Periodontal changes and osteoporosis
Pereira et al.
Table 1 Mean values of periodontal parameters after 3 years in those women with an initial diagnosis of normal bone as their systemic bone condition Normal bone (n 8)
Osteopenia (n 5)
Periodontal variables
Initial 3 years p Value
Initial 3 years
Gingival bleeding index (%) Visible plaque index (%) Probing depth (mm) Clinical attachment level (mm)
35.69 46.95 1.74 1.96
14.14 41.26 2.18 2.02
42.25 58.65 1.76 2.17
0.255 0.014* 0.469 0.165
59.89 57.65 1.79 2.31
Osteoporosis (n 2)
p Value
Initial 3 years p Value
0.010* 40.62 0.108 75.51 2.05 0.001* 0.052 1.50
74.37 62.81 1.37 2.80
0.035* 0.141 0.123 0.053
*, Statistically significant differences, t-test for paired samples (α 0.05)
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between the periodontal parameters (mean of GBI, VPI, PD, CAL) in the two time periods studied (initial and 3 years after) in all groups (normal bone condition, osteopenia and osteoporosis). The level of significance was set at 5% (p 0.05).
osteoporosis. It was observed, after 3 years, that the systemic bone mineral density showed the same diagnosis and that the mean of the GBI increased significantly (p 0.022).
DISCUSSION RESULTS After 3 years of the longitudinal study, 33 women were included in the final sample. Table 1 shows the measures of central tendency of the periodontal parameters of the group of women who presented normal bone status at the beginning of the study (n 15). It was observed that eight women remained diagnosed with normal bone condition after 3 years, and a statistically significant increase in VPI in this group was noted (p 0.014). Five women progressed to osteopenia; among them, there was a significant reduction in mean PD (p 0.001), without significant changes in other periodontal parameters. In addition, there was a significant increase in the GBI in the group of women who progressed to osteoporosis (p 0.035). Table 2 presents the mean of periodontal parameters among women who started the study with a diagnosis of osteopenia. It was observed that those women who remained with osteopenia (n 10) showed a reduction in PD (p 0.001), but no significant change in other periodontal parameters. Two patients progressed to osteoporosis and showed a significant increase in GBI after 3 years (p 0.001). Table 3 presents the average distribution of periodontal parameters in the group of women initially diagnosed with
Although periodontal disease is localized and osteoporosis represents a systemic condition, both show bone loss as their main feature and share many other aspects such as hormonal influence and the presence of cytokines14. Therefore, it is necessary to clarify the real influence of systemic bone density on periodontal bone condition23, since it is known that some systemic factors that contribute to bone mass loss are also factors that influence the progression of periodontal disease, such as advanced age, glucocorticoid therapy and immune disorders, so affecting host susceptibility12. Considering these factors, it is reasonable that studies aiming to investigate the possible relationship between BMD and progression of periodontal disease be conducted14. The results of this study suggest that, over nearly 3 years, some patients had a change in their systemic bone condition. Of the 33 patients evaluated in the study, 15 had the initial diagnosis of normal bone, and, after 3 years, only eight patients had this same bone condition, as there was a progression to osteopenia in five patients and to osteoporosis in two. Postmenopausal women who modified their condition to osteopenia and osteoporosis showed a significant increase in GBI, suggesting that osteoporosis can be associated with worsening of signs of inflammation and increasing sites with
Table 2 Mean values of periodontal parameters after 3 years in those women with an initial diagnosis of osteopenia as their systemic bone condition Osteopenia (n 10)
Osteoporosis (n 2)
Periodontal variables
Initial
3 years
p Value
Initial
3 years
Gingival bleeding index (%) Visible plaque index (%) Probing depth (mm) Clinical attachment level (mm)
34.1 35.19 1.72 1.72
28.1 43.11 1.30 1.74
0.096 0.111 0.001* 0.299
22.1 35.12 1.95 1.90
61.5 41.50 1.43 2.24
p Value 0.001* 0.420 0.223 0.190
*, Statistically significant differences, t-test for paired samples (α 0.05)
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Table 3 Mean values of periodontal parameters after 3 years in those women with an initial diagnosis of osteoporosis as their systemic bone condition Osteoporosis (n 6) Periodontal variables
Initial
3 years
p Value
Gingival bleeding index (%) Visible plaque index (%) Probing depth (mm) Clinical attachment level (mm)
15.98 31.54 1.66 1.56
37.38 44.54 1.43 1.76
0.022* 0.070 0.094 0.189
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*, Statistically significant differences, t-test for paired samples (α 0.05)
disease activity in periodontal tissue. These findings confirm those found by Yoshihara and colleagues20 who observed a greater loss in periodontal attachment in groups with low BMD after 3 years follow-up, and reported a correlation between BMD and the number of sites that showed progression of attachment loss. Another longitudinal study that confirms these findings shows a greater loss in the level of periodontal attachment among women with osteopenia and osteoporosis 1 year after the first tests24. Thus, there is a trend to confirm the hypothesis that postmenopausal women with loss of BMD are more likely to be affected by changes in periodontal clinical parameters than women who remain with systemically normal bone tissue. In the present study, it was observed that, in the osteopenia group, two patients changed their condition to osteoporosis after 3 years, with a significant increase in the GBI in these cases. Another possible explanation for our results may be found in the relation between estrogen and gingival bleeding. According to Gürsoy and colleagues15, high levels of estrogen were not able to increase gingival bleeding in pregnant women, compared to the control group (low estrogen). The authors explain that great changes in estrogen levels during pregnancy impair the periodontal inflammatory response against bacteria, since gingival epithelium and leukocytes express estrogen receptors. Thus, the opposite can be found in women with alleged low estrogen rates, who may present an increased GBI, as detected in this study in postmenopausal women who have shown modification of systemic bone status. Although periodontitis is one of the most prevalent human diseases associated with bone loss, the mechanism of osteoclast formation and bone resorption in this disease is not yet fully clarified. It is known that some inflammatory cytokines are present in the periodontal tissues and during the initiation and progression of periodontitis, and the alveolar bone destruction is primarily mediated by them, including osteoporosis24. However, in the present study, alveolar bone destruction was investigated through the increased loss of clinical attachment, which was borderline (p 0.05), possibly due to the duration of the study, and possibly because 3 years were not sufficient for the development or further progression of periodontal disease.
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The association between osteoporosis and periodontal bone loss has been reported in several studies18–20 and can be explained by the hypothesis expounded by Lerner14 suggesting that estrogen deficiency, characteristic of women in postmenopause, has a pathogenic role, influencing bone remodeling in sites with inflammatory processes, as seen in periodontal disease. However, this association cannot yet be confirmed11,17, revealing that these studies have conflicting results and the relationship between these diseases remains uncertain. An alleged explanation for the variability of results in this subject can be linked to the diversity of methodologies, especially the variation of the criteria for diagnosis of periodontal disease. The frequency of periodontal disease may be influenced by the various criteria for diagnosis and these indicate variations in the association between osteoporosis and periodontal disease24. Considering this fact, we opted to measure clinical periodontal parameters in order to evaluate and compare periodontal status according to the change in BMD, rather than to categorize patients according to a diagnosed periodontal disease. A limitation present in many studies on this subject concerns the cross-sectional design, since this cannot be considered as sensitive as the longitudinal method, to verify the alterations in attachment level. Thus, longitudinal studies are considered the most appropriate way to study the association of periodontal bone loss and osteoporosis. Furthermore, the evaluation methods for periodontal condition used in this study, especially the rate of CAL, are considered to be the gold-standard parameter to diagnose periodontitis. However, this study has shown some limitations, as it was not possible to re-examine the complete initial sample. The power of the study may have been limited by the high proportion of drop-outs after 3 years. There was great difficulty in contacting the initial sample. In addition, some women in this period showed exclusion factors (submission to periodontal treatment in the last 6 months, diagnosis of diabetes mellitus, use of hormone therapy). This small sample size may have been responsible for the large variation in the periodontal parameters. Besides that, there was no record of nutritional condition, since there is a possible relation between obesity, periodontitis and osteoporosis25. The present findings suggest that periodontal changes can be associated with osteoporosis in postmenopausal women. These changes appear to be more related to increased inflammatory markers (GBI and VPI) than variables that can reflect bone destruction (PD and CAL). Given the above, the importance of early diagnosis of decreased systemic bone density is clear in order to guide preventive and therapeutic measures that prevent the establishment of a possible negative impact on periodontal tissues. Conflict of interest The authors report no confl ict of interest. The authors alone are responsible for the content and writing of this paper. Source of funding
Nil.
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Periodontal changes and osteoporosis
Pereira et al.
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References 1. Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Micro 2010;8:481–90 2. Kinane DF, Peterson M, Stathopoulou PG. Environmental and other modifying factors of the periodontal diseases. Periodontol 2000 2006;40:107–19 3. Kaur S, White S, Bartold PM. Periodontal disease and rheumatoid arthritis: a systematic review. J Dent Res 2013;92:399–408 4. Nibali L, Tatarakis N, Needleman I, et al. Association between metabolic syndrome and periodontitis: a systematic review and meta-analysis. J Clin Endocrinol Metab 2013;98:913–20 5. Ide M, Papapanou PN. Epidemiology of association between maternal periodontal disease and adverse pregnancy outcomes – systematic review. J Clin Periodontol 2013;40(Suppl 14): S181–94 6. Chambrone L, Foz AM, Guglielmetti MR, et al. Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. J Clin Periodontol 2013;40:443–56 7. Lockhart PB, Bolger AF, Papapanou PN, et al. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association? Circulation 2012;125:2520–44 8. Megson E, Kapellas K, Bartold PM. Relationship between periodontal disease and osteoporosis. Int J Evid Based Healthcare 2010;8:129–39 9. Tezal M, Wactawski-Wende J, Grossi SG, Ho AW, Dunford R, Genco RJ. The relationship between bone mineral density and periodontitis in postmenopausal women. J Periodontol 2000;71:1492–8 10. Holroyd C, Cooper C, Dennison E. Epidemiology of osteoporosis. Best Pract Res Clin Endocrinol Metab 2008;22:671–85 11. Sultan N, Rao J. Association between periodontal disease and bone mineral density in postmenopausal women: a cross sectional study. Med Oral Patol Oral Cir Bucal 2011;16:440–7 12. Martinez-Maestre MA, González-Cejudo C, Machuca G, Torrejón R, Castelo-Branco C. Periodontits and osteoporosis: a systematic review. Climacteric 2010;13:523–9 13. Shu L, Guan SM, Fu SM, Guo T, Cao M, Ding Y. Estrogen modulates cytokine expression in human periodontal ligament cells. J Dent Res 2008;87:142–7 14. Lerner UH. Bone remodeling in post-menopausal osteoporosis. J Dent Res 2006;85:584–95
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15. Gürsoy M, Gürsoy UK, Sorsa T, Pajukanta R, Könönen E. High salivary estrogen and risk of developing pregnancy gingivitis. J Periodontol 2013;84:1281–9 16. Takahashi O, Yoshihara A, Nakamura K, Miyazaki H. Association between periodontitis and systemic bone mineral density in Japanese community-dwelling postmenopausal women. J Dent 2012;40:304–11 17. Babür C, Özcan G, Çebi DU, et al. Gingival crevicular fluid levels of osteoprotegerin (OPG) in premenopausal and postmenopausal women with or without chronic periodontitis. J Dent 2012;40:364–71 18. Kumar S, Kumar V, Patel P, Shashikumar P, Shashikumar Y, Vishwanath S. Correlation of periodontal status and bone mineral density in postmenopausal women: a digital radiographic and quantitative ultrasound study. Indian J Dent Res 2011; 22:270–6 19. Lopes FF, Loureiro FHF, Pereira AFV, Pereira ALA, Alves CMC. Association between osteoporosis and periodontal disease. Rev Bras Ginecol Obstet 2008;30:379–83 20. Yoshihara A, Seida Y, Hanada N, Miyazaki H. A longitudinal study of the relationship between periodontal disease and bone mineral density in community-dwelling older adults. J Clin Periodontol 2004;31:680–4 21. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994;843:1–129 22. Habashneh RA, Alchalabi H, Khader YS, Hazza’a AM, Odati Z, Johnson GK. Association between periodontal disease and osteoporosis in postmenopausal women in Jordan. J Periodontol 2010;81:1613–21 23. Pepelassi E, Nicopoulou-Karayianni K, Archontopoulou AD, et al. The relationship between osteoporosis and periodontitis in women aged 45–70 years. Oral Dis 2012;18:353–9 24. LaMonte MJ, Hovey KM, Genco RJ, Millen AE, Trevisan M, Wactawski-Wende J. Five-year changes in periodontal disease measures among postmenopausal females: the Buffalo Osteoperio Study. J Periodontol 2013;84:572–84 25. Palomo L, Buenocamino MC, Thacker H. Body mass index and periodontal health are correlated in postmenopausal women with low bone density. Int J Endocrinol Metab 2011;9:364–8
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Association between periodontal changes and osteoporosis in postmenopausal women F. M. B. G. Pereira, V. P. Rodrigues, A. E. F. de Oliveira, L. M. O. Brito* and F. F. Lopes Postgraduate Dentistry Program, Federal University of Maranhão, São Luís, Maranhão; *Department of Medicine III, Federal University of Maranhão, São Luís, Maranhão, Brazil Key words: OSTEOPOROSIS, OSTEOPENIA, BONE DENSITY, POSTMENOPAUSAL, PERIODONTAL DISEASES
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ABSTRACT Objective To investigate the possible association between periodontal changes and osteoporosis in postmenopausal women through a longitudinal study. Methods This longitudinal study included 33 patients. The participants were divided into three groups according to the bone mineral density assessed in the lumbar region: normal bone (G1, n 15), osteopenia (G2, n 12) and osteoporosis (G3, n 6). Periodontal evaluation included clinical attachment level, probing depth, gingival bleeding index and visible plaque index, evaluated by two examiners blinded to systemic bone condition. The statistical process included the t-test for paired samples, with a significance level of 5% to check for changes in periodontal parameters considered at initial and final systemic bone density. Results The results showed that, after follow-up, there was a significant increase in gingival bleeding index in the group of women who had normal initial bone condition and progressed to osteopenia (after 3 years, 59.89%, p 0.010) and osteoporosis (after 3 years, 74.37%, p 0.035). In addition, the group diagnosed with osteopenia at baseline who progressed to osteoporosis after 3 years also showed a significant increase in gingival bleeding index (p 0.001). Conclusions The findings suggest that periodontal changes can be associated with osteoporosis in postmenopausal women.
INTRODUCTION Periodontal disease is characterized as an immuno-inflammatory process triggered by the accumulation of biofilm on the outer surface of the tooth, which may eventually lead to destruction of periodontal ligament and alveolar bone1. Despite the dependence on primary bacterial etiologic factors, various behavioral factors, metabolic, hormonal and genetic, may modify the host response to biofilm, making it more susceptible to the development and progression of periodontitis2. Recent systematic reviews and meta-analyses of epidemiological studies suggest possible associations between periodontal disease and several systemic conditions: rheumatoid arthritis3, metabolic syndrome4, adverse pregnancy outcomes5, chronic kidney disease6, atherosclerosis7, and among them, osteoporosis8. The multifactorial nature of periodontal disease suggests that osteoporosis can act as an additional
predisposing factor, since the systemic factors responsible for osteoporosis may interact with local factors to increase the pattern of alveolar bone loss9. Data on the prevalence of osteoporosis are scarce and discontinuous, but it is estimated that approximately 10 million people over the age of 50 have osteoporosis10. This injury is correlated with menopause and decreased estradiol levels, as well as the main circulating estrogen. In this group of women, a cortical bone loss of 2–3% and a trabecular bone loss of 4–8% per year can be observed, leading to increased risk of fractures, especially in the hip and forearm11. The biological plausibility of the association between osteoporosis and periodontal disease may be related to the presence of several common risk factors such as tobacco use, poor nutritional status, advanced age, therapy with glucocorticoids, and immune disorders12. Although they have different primary etiologies, both diseases show increased produc-
Correspondence: Professor Dra F. F. Lopes, Universidade Federal do Maranhão, Programa de Pós-Graduação em Odontologia, Avenida dos Portugueses, s/n, Campus Universit ário do Bacanga, CEP: 65.085-580, São Luís, Maranhão, Brazil; E-mail: [email protected] ORIGINAL ARTICLE © 2014 International Menopause Society DOI: 10.3109/13697137.2014.966239
Received 07-07-2014 Revised 12-09-2014 Accepted 12-09-2014
Periodontal changes and osteoporosis
Climacteric Downloaded from informahealthcare.com by Korea University on 12/30/14 For personal use only.
tion of cytokines that stimulate osteoclast activity13. Besides that, estrogen receptors are expressed in bone and immune cells, and thus it has been suggested that changes in tissue levels of estrogen might also influence bone metabolism in periodontal sites with inflammatory processes, since the periodontal ligament cells express specific membrane receptors for estrogens14. Based on studies that have addressed the association between periodontal disease and osteoporosis which have found conflicting results15–20, and especially the lack of studies of longitudinal design, which may further elucidate the interaction between these two diseases, the present study investigates the possible association between periodontal changes and osteoporosis in postmenopausal women with a follow-up of 3 years.
METHODS This longitudinal, observational study was designed to determine the influence of systemic bone status on the periodontal status of postmenopausal women. The study group was composed of women aged 45–77 years who were recruited at Materno Infantil University Hospital (HUMI), of the Federal University of Maranhão (UFMA), located in São Luís, Maranhão. The inclusion criterion adopted was confirmation that the menstrual cycle had ceased for over 1 year; the exclusion criteria were the condition of less than six teeth, submission to periodontal treatment in the last 6 months, use of hormone replacement therapy (HRT), smoking history and diabetes mellitus. After all exclusions, the initial population consisted of 99 postmenopausal women. All these patients signed an informed consent form to participate in the study, the protocol for which was approved by the Research Ethics Committee of UFMA’s Presidente Dutra University Hospital (Notion n°. 172/08). The variables collected included data regarding systemic bone status and evaluation of the periodontal status of women in postmenopause. Participants were divided into three groups according to the classification of bone mass. The diagnosis
Figure 1
2
Pereira et al. of bone mineral density (BMD) was performed by bone densitometry using dual-energy X-ray absorptiometry (Lunar, USA) in the patient’s lumbar area (L2–L4 vertebrae). According to the World Health Organization criteria21, BMD variation difference was measured, in relation to that expected for healthy young women. After this procedure, three groups were formed: Group 1 normal bone (T-score 1), Group 2 osteopenia (T-scores between 1 and 2.5), and Group 3 osteoporosis (T-score 2.5). Two examiners performed the periodontal evaluation (κ 0.81). They were trained and blinded to the systemic bone status condition of patients. A clinical mirror and millimetered periodontal probe were used (Williams, Hu-Friedy, Chicago, IL, USA). The gingival bleeding index (GBI) and visible plaque index (VPI) were recorded in similar methodology as used by Habashneh and colleagues22, in which the measurements were obtained from four sites on each tooth (mesial, distal, buccal and lingual). Furthermore, the loss of support periodontal tissue was assessed by measurements of clinical probing depth (PD) and clinical attachment level (CAL), which were obtained from six sites on each tooth (mesiobuccal, mid-buccal, disto-buccal, mesio-lingual, mid-lingual and disto-lingual). Measurements were obtained from all teeth, except the third molars. The PD was defined as the distance from the gingival margin to the bottom of the periodontal pocket or gingival sulcus and the CAL was the distance from the cement–enamel junction to the bottom of the periodontal pocket or gingival sulcus, both measured in millimeters. Among the 99 women in the initial sample, only 33 women returned for reassessment after 3 years, and these made up the final sample for this study (Figure 1). The reasons for not returning for the follow-up (67%) were: change of address, submission to periodontal treatment in the last 6 months, diagnosis of diabetes mellitus, use of HRT and refusal to participate. The SPSS statistical program (version 17.0) was used to analyze the data. Initially, a descriptive analyses of the data were performed by averaging. The Shapiro–Wilk test was used to assess the normality of data distribution. The t-test for paired samples was used to determine statistical differences
Flowchart of monitoring and reassessment steps
Climacteric
Periodontal changes and osteoporosis
Pereira et al.
Table 1 Mean values of periodontal parameters after 3 years in those women with an initial diagnosis of normal bone as their systemic bone condition Normal bone (n 8)
Osteopenia (n 5)
Periodontal variables
Initial 3 years p Value
Initial 3 years
Gingival bleeding index (%) Visible plaque index (%) Probing depth (mm) Clinical attachment level (mm)
35.69 46.95 1.74 1.96
14.14 41.26 2.18 2.02
42.25 58.65 1.76 2.17
0.255 0.014* 0.469 0.165
59.89 57.65 1.79 2.31
Osteoporosis (n 2)
p Value
Initial 3 years p Value
0.010* 40.62 0.108 75.51 2.05 0.001* 0.052 1.50
74.37 62.81 1.37 2.80
0.035* 0.141 0.123 0.053
*, Statistically significant differences, t-test for paired samples (α 0.05)
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between the periodontal parameters (mean of GBI, VPI, PD, CAL) in the two time periods studied (initial and 3 years after) in all groups (normal bone condition, osteopenia and osteoporosis). The level of significance was set at 5% (p 0.05).
osteoporosis. It was observed, after 3 years, that the systemic bone mineral density showed the same diagnosis and that the mean of the GBI increased significantly (p 0.022).
DISCUSSION RESULTS After 3 years of the longitudinal study, 33 women were included in the final sample. Table 1 shows the measures of central tendency of the periodontal parameters of the group of women who presented normal bone status at the beginning of the study (n 15). It was observed that eight women remained diagnosed with normal bone condition after 3 years, and a statistically significant increase in VPI in this group was noted (p 0.014). Five women progressed to osteopenia; among them, there was a significant reduction in mean PD (p 0.001), without significant changes in other periodontal parameters. In addition, there was a significant increase in the GBI in the group of women who progressed to osteoporosis (p 0.035). Table 2 presents the mean of periodontal parameters among women who started the study with a diagnosis of osteopenia. It was observed that those women who remained with osteopenia (n 10) showed a reduction in PD (p 0.001), but no significant change in other periodontal parameters. Two patients progressed to osteoporosis and showed a significant increase in GBI after 3 years (p 0.001). Table 3 presents the average distribution of periodontal parameters in the group of women initially diagnosed with
Although periodontal disease is localized and osteoporosis represents a systemic condition, both show bone loss as their main feature and share many other aspects such as hormonal influence and the presence of cytokines14. Therefore, it is necessary to clarify the real influence of systemic bone density on periodontal bone condition23, since it is known that some systemic factors that contribute to bone mass loss are also factors that influence the progression of periodontal disease, such as advanced age, glucocorticoid therapy and immune disorders, so affecting host susceptibility12. Considering these factors, it is reasonable that studies aiming to investigate the possible relationship between BMD and progression of periodontal disease be conducted14. The results of this study suggest that, over nearly 3 years, some patients had a change in their systemic bone condition. Of the 33 patients evaluated in the study, 15 had the initial diagnosis of normal bone, and, after 3 years, only eight patients had this same bone condition, as there was a progression to osteopenia in five patients and to osteoporosis in two. Postmenopausal women who modified their condition to osteopenia and osteoporosis showed a significant increase in GBI, suggesting that osteoporosis can be associated with worsening of signs of inflammation and increasing sites with
Table 2 Mean values of periodontal parameters after 3 years in those women with an initial diagnosis of osteopenia as their systemic bone condition Osteopenia (n 10)
Osteoporosis (n 2)
Periodontal variables
Initial
3 years
p Value
Initial
3 years
Gingival bleeding index (%) Visible plaque index (%) Probing depth (mm) Clinical attachment level (mm)
34.1 35.19 1.72 1.72
28.1 43.11 1.30 1.74
0.096 0.111 0.001* 0.299
22.1 35.12 1.95 1.90
61.5 41.50 1.43 2.24
p Value 0.001* 0.420 0.223 0.190
*, Statistically significant differences, t-test for paired samples (α 0.05)
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Table 3 Mean values of periodontal parameters after 3 years in those women with an initial diagnosis of osteoporosis as their systemic bone condition Osteoporosis (n 6) Periodontal variables
Initial
3 years
p Value
Gingival bleeding index (%) Visible plaque index (%) Probing depth (mm) Clinical attachment level (mm)
15.98 31.54 1.66 1.56
37.38 44.54 1.43 1.76
0.022* 0.070 0.094 0.189
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*, Statistically significant differences, t-test for paired samples (α 0.05)
disease activity in periodontal tissue. These findings confirm those found by Yoshihara and colleagues20 who observed a greater loss in periodontal attachment in groups with low BMD after 3 years follow-up, and reported a correlation between BMD and the number of sites that showed progression of attachment loss. Another longitudinal study that confirms these findings shows a greater loss in the level of periodontal attachment among women with osteopenia and osteoporosis 1 year after the first tests24. Thus, there is a trend to confirm the hypothesis that postmenopausal women with loss of BMD are more likely to be affected by changes in periodontal clinical parameters than women who remain with systemically normal bone tissue. In the present study, it was observed that, in the osteopenia group, two patients changed their condition to osteoporosis after 3 years, with a significant increase in the GBI in these cases. Another possible explanation for our results may be found in the relation between estrogen and gingival bleeding. According to Gürsoy and colleagues15, high levels of estrogen were not able to increase gingival bleeding in pregnant women, compared to the control group (low estrogen). The authors explain that great changes in estrogen levels during pregnancy impair the periodontal inflammatory response against bacteria, since gingival epithelium and leukocytes express estrogen receptors. Thus, the opposite can be found in women with alleged low estrogen rates, who may present an increased GBI, as detected in this study in postmenopausal women who have shown modification of systemic bone status. Although periodontitis is one of the most prevalent human diseases associated with bone loss, the mechanism of osteoclast formation and bone resorption in this disease is not yet fully clarified. It is known that some inflammatory cytokines are present in the periodontal tissues and during the initiation and progression of periodontitis, and the alveolar bone destruction is primarily mediated by them, including osteoporosis24. However, in the present study, alveolar bone destruction was investigated through the increased loss of clinical attachment, which was borderline (p 0.05), possibly due to the duration of the study, and possibly because 3 years were not sufficient for the development or further progression of periodontal disease.
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The association between osteoporosis and periodontal bone loss has been reported in several studies18–20 and can be explained by the hypothesis expounded by Lerner14 suggesting that estrogen deficiency, characteristic of women in postmenopause, has a pathogenic role, influencing bone remodeling in sites with inflammatory processes, as seen in periodontal disease. However, this association cannot yet be confirmed11,17, revealing that these studies have conflicting results and the relationship between these diseases remains uncertain. An alleged explanation for the variability of results in this subject can be linked to the diversity of methodologies, especially the variation of the criteria for diagnosis of periodontal disease. The frequency of periodontal disease may be influenced by the various criteria for diagnosis and these indicate variations in the association between osteoporosis and periodontal disease24. Considering this fact, we opted to measure clinical periodontal parameters in order to evaluate and compare periodontal status according to the change in BMD, rather than to categorize patients according to a diagnosed periodontal disease. A limitation present in many studies on this subject concerns the cross-sectional design, since this cannot be considered as sensitive as the longitudinal method, to verify the alterations in attachment level. Thus, longitudinal studies are considered the most appropriate way to study the association of periodontal bone loss and osteoporosis. Furthermore, the evaluation methods for periodontal condition used in this study, especially the rate of CAL, are considered to be the gold-standard parameter to diagnose periodontitis. However, this study has shown some limitations, as it was not possible to re-examine the complete initial sample. The power of the study may have been limited by the high proportion of drop-outs after 3 years. There was great difficulty in contacting the initial sample. In addition, some women in this period showed exclusion factors (submission to periodontal treatment in the last 6 months, diagnosis of diabetes mellitus, use of hormone therapy). This small sample size may have been responsible for the large variation in the periodontal parameters. Besides that, there was no record of nutritional condition, since there is a possible relation between obesity, periodontitis and osteoporosis25. The present findings suggest that periodontal changes can be associated with osteoporosis in postmenopausal women. These changes appear to be more related to increased inflammatory markers (GBI and VPI) than variables that can reflect bone destruction (PD and CAL). Given the above, the importance of early diagnosis of decreased systemic bone density is clear in order to guide preventive and therapeutic measures that prevent the establishment of a possible negative impact on periodontal tissues. Conflict of interest The authors report no confl ict of interest. The authors alone are responsible for the content and writing of this paper. Source of funding
Nil.
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Periodontal changes and osteoporosis
Pereira et al.
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