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Alveolar bone height in patients after liver transplantation1
Alveolar Bone Height in Patients After Liver Transplantation S. Barak, E.E. Machtei, O. Oettinger-Barak, M. Peled, L. Ardekian, D. Laufer, and Y. Baruch
O
NE of the known complications after liver transplantation is the loss of bone mass.1 Regardless of the preoperative bone density, most liver transplantees will suffer bone loss during the first months after transplantation.2,3 This bone loss is attributed to the effect of the transplantation itself,3 but the associated steroidal therapy is also considered a significant contributory factor.2 Bone loss may also be the result of the underlying liver disease. Cirrhotic patients show a significant decrease in bone mass, reduced bone formation, and significant disorders of bone mineral metabolism.4 The role of cyclosporine A (CyA) in aggravating bone loss is controversial, in light of conflicting data reported in both in vivo and in vitro experimental studies: While CyA has been shown in vitro to decrease bone resorption and rate of osteoclast formation,5 in vivo studies have shown an increase in histologic parameters of bone loss.6 Furthermore, the use of FK 506 instead of CyA has not been shown to be of any advantage with regard to loss of bone mass.7 The purpose of the present study was to evaluate the effect of liver transplantation and concomitant immunosuppressive (IS) therapy on alveolar bone height.
in the transplanted patients was 65.7 ⫾ 10.3 months, and the range was 2 to 156 months. All patients underwent a standardized panoramic radiograph, which was then digitized and stored electronically. Next, using a computer-based measurement software (X-view Inc, Jerusalem), the height of the alveolar bone crest was measured from a fixed reference point (the cemento-enamel junction) proximal to all available teeth, excluding third molars. Unpaired Student’s t-test served to compare alveolar bone loss in experimental versus control groups in Gi-variant model. Analysis of variance (ANOVA) was used to assess the differences between the three groups. Pearson’s correlation coefficient test was used to assess the correlation between the time interval since liver transplantation and the extent of alveolar bone loss.
RESULTS
PATIENTS AND METHODS
Patient’s demographics and alveolar bone loss are presented in Table 1. Mean age in the post–liver transplantation group (49.91 ⫾ 2.51 years) was almost identical to that of the control (49.1 ⫾ 3.90 years) and the liver cirrhosis patients (50.16 ⫾ 3.81 years). These differences where statistically insignificant (P ⫽ .9772). To the contrary, alveolar bone loss in the transplanted patients (4.67 ⫾ 0.60 mm) was twice greater than that in the control group (2.47 ⫾ 0.13 mm). These differences were statistically significant (P ⫽ .032, Student’s t-test).
Patients attending the liver clinic at the Rambam Medical Center, Haifa, Israel, were invited to join this study. They consisted of two subgroups: (1) eight patients who had advanced liver cirrhosis and had not undergone liver transplantation; (2) 22 patients who had undergone liver transplantation and were currently on an IS protocol with either CyA or FK 506. A control group of 17 age- and gender-matched healthy subjects was formed from subjects attending the maxillofacial outpatients clinic without any systemic disease. There were a total of 24 women and 23 men. Ages ranged from 30 to 71 years (mean, 49.7 ⫾ 11.4 SD), with marked similarity between groups (Table 1). The mean interval post–liver transplant
From the Faculty of Medicine, Technion Israeli Institute of Technology; Department of Oral and Maxillofacial Surgery; and Liver Unit, Department of Internal Medicine B, Rambam Medical Center, Haifa, Israel. This work is toward partial fulfillment for a medical doctor degree at the faculty of medicine, Technion Israeli Institute of Technology, Haifa, Israel. Address reprint requests to Dr Yaacov Baruch, Department of Internal Medicine B, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel.
Table 1. Alveolar Bone Loss and Demographics Variable
Posttransplant (⫾SE)
Pretransplant (⫾SE)
Control
P*
N Age (y) CEJ-BC† (mm) rCEJ-BC‡ (mm)
22 49.91 ⫾ 2.51 4.67 ⫾ 0.60 4.72 ⫾ 0.59
8 49.1 ⫾ 3.90 5.68 ⫾ 0.57 5.24 ⫾ 0.73
17 50.16 ⫾ 3.81 2.47 ⫾ 0.13 2.28 ⫾ 0.17
— .9772 .0009 .001
*Analysis of variance. † Cementoenamel junction to bone crest. ‡ Cementoenamel junction to bone crest—index teeth.
0041-1345/00/$–see front matter PII S0041-1345(00)00956-8 718
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 32, 718–720 (2000)
ALVEOLAR BONE POST LTX
719
Fig 1. A moderate negative correlation between alveolar bone loss and the time interval since liver transplantation is clearly visible.
The correlation between bone loss and time interval since liver transplantation is presented in Figure 1. A moderate negative correlation was found (R ⫽ 0.447, P ⫽ .0484). Bone loss in patients before transplantation (5.68 ⫾ 0.57 mm) was also significantly higher than the controls (P ⫽ .0009, ANOVA). DISCUSSION
This is the first study attempting to find the association between liver disease, transplantation, and alveolar bone height. In the present study, cirrhotic and post–liver transplantation patients exhibited significantly greater alveolar bone loss compared to matched healthy controls. The alveolar bone is unique in its ability to undergo rapid and continuous remodeling.8 Currently, there is very little data on the relationship between radiographic alveolar bone loss and either liver disease, transplantation, and/or IS therapy. Bone loss immediately after transplantation is a well-known complication that has been previously described.1 This phenomenon might also be associated with the underlying liver disease.4 Lassila and Virtanen9 reported a decrease in osteoblastic activity in the alveolar bone after experimental liver injury and mechanical stress in rats. Therefore, the greater alveolar bone loss observed in our patients might reflect the extent of bone loss accumulated through the years before the liver transplantation. This possible mech-
anism is supported by the greater bone loss observed in the small subgroup of liver cirrhosis patients which did not yet receive liver transplantation. A significant reverse correlation was observed between the time interval since liver transplantation and IS therapy and the extent of alveolar bone loss. This might be attributed to either the restoration of liver function or to the concomitant IS medication. The effect of the latter has been shown by Fu et al10 who noted an increase in alveolar bone remodeling in animals treated with CyA. To the contrary, Fischer and Klinge11 in CyA-treated rats noted a greater bone resorption in the experimental periodontitis areas versus healthy sites. Further studies will be needed to fully appreciate the alveolar bone changes after liver transplantation and IS therapy. Prevention of alveolar bone loss will improve the periodontal condition of these patients; therefore it will prevent tooth loss associated with this disease.
REFERENCES 1. Katz IA, Epstein S: J Bone Miner Res 7:123, 1992 2. McDonald JA, Dustan CR, Dilworth P, et al: Hepatology 14:613, 1991 3. Meys E, Fontanges E, Furcade N, et al: Am J Med 97:445, 1994
720 4. Diamond TH, Stiel D, Lunzer M, et al: Gastroenterology 96:213, 1989 5. Stewart PJ, Green OC, Stern PH: J Bone Miner Res 1:285, 1986 6. Movsowitz C, Epstein S, Fallon M: Endocrinology 123:2571, 1988 7. Park KM, Hay JE, Lee SG, et al: Transplant Proc 28:1738, 1996 8. Lindhe J, Karring T: In Lindhe J, (ed): Clinical Periodontol-
BARAK, MACHTEI, OETTINGER-BARAK ET AL ogy and Implant Dentistry, 3rd Ed. Copenhagen: Munksgaard; 1997, p 52 9. Lassila V, Virtanen P: Acta Anat (Basal) 118:116, 1984 10. Fu E, Nieh S, Wikesjo UM, et al: J Periodontol 68:1231, 1997 11. Fischer RG, Klinge B: J Clin Periodontol 21:240, 1994
O
NE of the known complications after liver transplantation is the loss of bone mass.1 Regardless of the preoperative bone density, most liver transplantees will suffer bone loss during the first months after transplantation.2,3 This bone loss is attributed to the effect of the transplantation itself,3 but the associated steroidal therapy is also considered a significant contributory factor.2 Bone loss may also be the result of the underlying liver disease. Cirrhotic patients show a significant decrease in bone mass, reduced bone formation, and significant disorders of bone mineral metabolism.4 The role of cyclosporine A (CyA) in aggravating bone loss is controversial, in light of conflicting data reported in both in vivo and in vitro experimental studies: While CyA has been shown in vitro to decrease bone resorption and rate of osteoclast formation,5 in vivo studies have shown an increase in histologic parameters of bone loss.6 Furthermore, the use of FK 506 instead of CyA has not been shown to be of any advantage with regard to loss of bone mass.7 The purpose of the present study was to evaluate the effect of liver transplantation and concomitant immunosuppressive (IS) therapy on alveolar bone height.
in the transplanted patients was 65.7 ⫾ 10.3 months, and the range was 2 to 156 months. All patients underwent a standardized panoramic radiograph, which was then digitized and stored electronically. Next, using a computer-based measurement software (X-view Inc, Jerusalem), the height of the alveolar bone crest was measured from a fixed reference point (the cemento-enamel junction) proximal to all available teeth, excluding third molars. Unpaired Student’s t-test served to compare alveolar bone loss in experimental versus control groups in Gi-variant model. Analysis of variance (ANOVA) was used to assess the differences between the three groups. Pearson’s correlation coefficient test was used to assess the correlation between the time interval since liver transplantation and the extent of alveolar bone loss.
RESULTS
PATIENTS AND METHODS
Patient’s demographics and alveolar bone loss are presented in Table 1. Mean age in the post–liver transplantation group (49.91 ⫾ 2.51 years) was almost identical to that of the control (49.1 ⫾ 3.90 years) and the liver cirrhosis patients (50.16 ⫾ 3.81 years). These differences where statistically insignificant (P ⫽ .9772). To the contrary, alveolar bone loss in the transplanted patients (4.67 ⫾ 0.60 mm) was twice greater than that in the control group (2.47 ⫾ 0.13 mm). These differences were statistically significant (P ⫽ .032, Student’s t-test).
Patients attending the liver clinic at the Rambam Medical Center, Haifa, Israel, were invited to join this study. They consisted of two subgroups: (1) eight patients who had advanced liver cirrhosis and had not undergone liver transplantation; (2) 22 patients who had undergone liver transplantation and were currently on an IS protocol with either CyA or FK 506. A control group of 17 age- and gender-matched healthy subjects was formed from subjects attending the maxillofacial outpatients clinic without any systemic disease. There were a total of 24 women and 23 men. Ages ranged from 30 to 71 years (mean, 49.7 ⫾ 11.4 SD), with marked similarity between groups (Table 1). The mean interval post–liver transplant
From the Faculty of Medicine, Technion Israeli Institute of Technology; Department of Oral and Maxillofacial Surgery; and Liver Unit, Department of Internal Medicine B, Rambam Medical Center, Haifa, Israel. This work is toward partial fulfillment for a medical doctor degree at the faculty of medicine, Technion Israeli Institute of Technology, Haifa, Israel. Address reprint requests to Dr Yaacov Baruch, Department of Internal Medicine B, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel.
Table 1. Alveolar Bone Loss and Demographics Variable
Posttransplant (⫾SE)
Pretransplant (⫾SE)
Control
P*
N Age (y) CEJ-BC† (mm) rCEJ-BC‡ (mm)
22 49.91 ⫾ 2.51 4.67 ⫾ 0.60 4.72 ⫾ 0.59
8 49.1 ⫾ 3.90 5.68 ⫾ 0.57 5.24 ⫾ 0.73
17 50.16 ⫾ 3.81 2.47 ⫾ 0.13 2.28 ⫾ 0.17
— .9772 .0009 .001
*Analysis of variance. † Cementoenamel junction to bone crest. ‡ Cementoenamel junction to bone crest—index teeth.
0041-1345/00/$–see front matter PII S0041-1345(00)00956-8 718
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 32, 718–720 (2000)
ALVEOLAR BONE POST LTX
719
Fig 1. A moderate negative correlation between alveolar bone loss and the time interval since liver transplantation is clearly visible.
The correlation between bone loss and time interval since liver transplantation is presented in Figure 1. A moderate negative correlation was found (R ⫽ 0.447, P ⫽ .0484). Bone loss in patients before transplantation (5.68 ⫾ 0.57 mm) was also significantly higher than the controls (P ⫽ .0009, ANOVA). DISCUSSION
This is the first study attempting to find the association between liver disease, transplantation, and alveolar bone height. In the present study, cirrhotic and post–liver transplantation patients exhibited significantly greater alveolar bone loss compared to matched healthy controls. The alveolar bone is unique in its ability to undergo rapid and continuous remodeling.8 Currently, there is very little data on the relationship between radiographic alveolar bone loss and either liver disease, transplantation, and/or IS therapy. Bone loss immediately after transplantation is a well-known complication that has been previously described.1 This phenomenon might also be associated with the underlying liver disease.4 Lassila and Virtanen9 reported a decrease in osteoblastic activity in the alveolar bone after experimental liver injury and mechanical stress in rats. Therefore, the greater alveolar bone loss observed in our patients might reflect the extent of bone loss accumulated through the years before the liver transplantation. This possible mech-
anism is supported by the greater bone loss observed in the small subgroup of liver cirrhosis patients which did not yet receive liver transplantation. A significant reverse correlation was observed between the time interval since liver transplantation and IS therapy and the extent of alveolar bone loss. This might be attributed to either the restoration of liver function or to the concomitant IS medication. The effect of the latter has been shown by Fu et al10 who noted an increase in alveolar bone remodeling in animals treated with CyA. To the contrary, Fischer and Klinge11 in CyA-treated rats noted a greater bone resorption in the experimental periodontitis areas versus healthy sites. Further studies will be needed to fully appreciate the alveolar bone changes after liver transplantation and IS therapy. Prevention of alveolar bone loss will improve the periodontal condition of these patients; therefore it will prevent tooth loss associated with this disease.
REFERENCES 1. Katz IA, Epstein S: J Bone Miner Res 7:123, 1992 2. McDonald JA, Dustan CR, Dilworth P, et al: Hepatology 14:613, 1991 3. Meys E, Fontanges E, Furcade N, et al: Am J Med 97:445, 1994
720 4. Diamond TH, Stiel D, Lunzer M, et al: Gastroenterology 96:213, 1989 5. Stewart PJ, Green OC, Stern PH: J Bone Miner Res 1:285, 1986 6. Movsowitz C, Epstein S, Fallon M: Endocrinology 123:2571, 1988 7. Park KM, Hay JE, Lee SG, et al: Transplant Proc 28:1738, 1996 8. Lindhe J, Karring T: In Lindhe J, (ed): Clinical Periodontol-
BARAK, MACHTEI, OETTINGER-BARAK ET AL ogy and Implant Dentistry, 3rd Ed. Copenhagen: Munksgaard; 1997, p 52 9. Lassila V, Virtanen P: Acta Anat (Basal) 118:116, 1984 10. Fu E, Nieh S, Wikesjo UM, et al: J Periodontol 68:1231, 1997 11. Fischer RG, Klinge B: J Clin Periodontol 21:240, 1994