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The combination syndrome: A literature review

Sigvard Palmqvist, LDS, Odont Dr,a Gunnar E. Carlsson, LDS, Odont Dr, Dr Odont hc,b and ¨ Bengt Owall, LDS, Odont Dr, Dr Med hcc School of Dentistry, University of Copenhagen, Copenhagen, Denmark; and School of Dentistry, Goteborg University, Goteborg, Sweden ¨ ¨
Although combination syndrome is recognized by many clinicians, documented observations seem to be rare. The aim of this article was to critically review the literature regarding combination syndrome to evaluate the evidence for this concept. A search of the dental literature with Medline/PubMed through July 2002, focusing on the combination syndrome and related features, was undertaken and combined with a hand search of older references and textbooks on removable prosthodontics. (J Prosthet Dent 2003;90:270-5.)

oss of bone of the anterior edentulous maxilla when opposed by natural mandibular anterior teeth is 1 of several features of the combination syndrome. Although recognized by many clinicians, documented observations seem to be rare. The Glossary of Prosthodontic Terms1 defines combination syndrome as “the characteristic features that occur when an edentulous maxilla is opposed by natural mandibular anterior teeth, including loss of bone from the anterior portion of the maxillary ridge, overgrowth of the tuberosities, papillary hyperplasia of the hard palatal mucosa, extrusion of mandibular anterior teeth, and loss of alveolar bone and ridge height beneath the mandibular removable partial denture bases, also called anterior hyperfunction syndrome.” Ellsworth Kelly2 was the first person to use the term “combination syndrome.” He followed a small group of patients wearing a complete maxillary denture opposed by mandibular anterior teeth and a distal extension distal removable partial denture (RPD). Of the 6 patients followed up for 3 years, all showed a reduction of the anterior bone in the maxilla along with enlarged tuberosities. For 5 patients there was an increased bone level of the tuberosities. Kelly2 blamed the mandibular RPD and the lack of a posterior seal in the maxillary denture for these changes. He discussed “excessive bony resorption under the mandibular removable partial denture bases” but provided no values. Kelly2 discussed various possibilities to avoid combination syndrome, including extraction of the mandibular teeth, but did not advocate this solution. Instead, he proposed using the roots of anterior mandibular teeth to support an overdenture. He also mentioned the option of using endodontic ima

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plants to preserve questionable roots for support in the posterior part of the mandible. A few years later, further characteristics were added to the combination syndrome: loss of vertical dimension of occlusion, occlusal plane discrepancy, anterior spatial repositioning of the mandible, poor adaptation of the prostheses, epulis fissuratum, and periodontal changes.3 However, these changes are not generally associated with combination syndrome. In spite of his emphasis on the negative role of the mandibular RPD, Kelly2 wrote: “The early loss of bone from the anterior part of the maxillary jaw is the key to the other changes of the combination syndrome.” This view was previously published in The American TextBook of Prosthetic Dentistry4 in 1907 in the following manner: “One of the most commonly observed cases of this sort (localized adsorption) is that in which a full upper plate denture is antagonized only by six or eight lower natural teeth, there being no teeth posterior to this point, adsorption of the alveolar process in the maxilla in front occurring as a result of the undue pressure on it.” Clinicians have recognized a number of the aforementioned features in some patients, but documented observations are rare. About 25 years after the publication of Kelly’s2 article, a review of sequelae of treatment with complete dentures argued that there was a lack of evidence for the combination syndrome.5 Today, accepting the principle of evidence-based dentistry, a critical review of the documentation behind the concept of “combination syndrome” seems warranted. The aim of this article was to evaluate the evidence for this concept.

LITERATURE REVIEW
A search of medical and dental literature through July 2002 was undertaken by use of Medline/PubMed. The focus of the search was on combination syndrome and related features such as alveolar bone loss, bone resorption, maxillary tuberosities, denture stomatitis, and maxillary abnormalities, all combined with removable partial denture variables. Along with the articles found
VOLUME 90 NUMBER 3

Professor emeritus, Department of Prosthetic Dentistry, University of Copenhagen. b Professor emeritus, Department of Prosthetic Dentistry, Goteborg ¨ University. c Professor and Chair, Department of Prosthetic Dentistry, University of Copenhagen. 270 THE JOURNAL OF PROSTHETIC DENTISTRY

20 In another study. This is supported by studies showing significant differences in residual alveolar bone between edentulous subjects wearing or not wearing removable dentures. In a 21-year follow-up of the same patients. It is inevitable and has been called “a major oral disease entity. With this technique. whereas an overdenture supported by 2 implants resulted in a continuous resorption of the same areas. which is more pronounced in the mandible than in the maxilla and has been demonstrated to occur for up to 30 years. and that the resorbed bone was not reshaped when pressure was discontinued. some common textbooks on removable prosthodontics were scrutinized for additional documentation. Bone resorption in the anterior part of the edentulous maxilla.10 After the initial remodeling phase. and (3) natural mandibular teeth only. Most studies have used radiographic cephalometry for measurement of residual ridge height. a reduction was noted in all groups without significant differences between them.”13 At the same center. However. the third group had an RPD retained by a bar splint uniting crowns. including bone resorption and a changed contour.28 Similar values were noted for both groups. In addition. the second group had a Class I mandibular RPD. CARLSSON. a fixed implant-supported prosthesis of the same design produced bone apposition in the posterior parts of the mandible. and factors other than the wearing of removable dentures may be involved in the resorption process.27 The bone resorption under complete maxillary dentures was also studied during a 5-year period in patients wearing either a conventional complete mandibular denture or an overdenture supported by roots of the mandibular canines. no difference or a smaller difference in resorption rate during this initial stage was found between the immediate technique and a healing period without denture. some cautious conclusions may be drawn by comparing results from available studies of various designs. (2) anterior mandibular teeth and a Class I mandibular RPD. 1 study7 compared bone resorption of the anterior maxilla in patients wearing a complete maxillary denture with different mandibular status: (1) mandibular complete denture.9.8.¨ PALMQVIST. An earlier longitudi271 . In the bar splint group no significant reduction in bone height was noted in the anterior maxilla. No statistically significant differences were found between these groups. When evaluating the horizontal dimension and calculating the anterior bone area of the maxillary residual ridge on the radiographs.05). in some situations. Residual ridge resorption— general aspects After extraction of teeth. the individual variations were still very large. the smallest resorbed area of the maxillary residual ridge.” has been the subject of many clinical reports and some inSEPTEMBER 2003 vestigations of series of patients.22-24 Maxillary ridge resorption in relation to mandibular status Mandibular natural teeth with or without RPD. great individual differences have been noted.19 Subjects not wearing dentures had more remaining bone. other groups of patients with a maxillary complete denture and various prosthodontic solutions for the partially edentulous mandible were also followed.11-13 However. AND OWALL THE JOURNAL OF PROSTHETIC DENTISTRY in Medline/PubMed.25. Most studies comprise only small groups of patients.6. However. Over a 5-year period there was a significant reduction of the measured height of the anterior maxillary bone in the first 2 groups with similar mean values for both groups. No longitudinal study with the extraction of the anterior maxillary teeth as the starting point and randomly chosen mandibular status exists.15-17 There are clear indications and little doubt that the removable denture plays an important causative role in the bone resorption process. However.7 The loss of bone in the maxilla was reported to be less if an immediate denture technique was used compared with a healing period without denture. calculated from the radiographs for the period between 6 months and 5 years after extraction.9 For the mandible. Grouping the subjects with complete dentures together with those with natural teeth including molars. was noted for group 3 (natural teeth only). and comparing them with a group having only anterior teeth (with or without an RPD) showed slightly greater bone resorption in the latter group which was significantly different (P . and there was no support for systematic development of “combination syndrome. the basal bone.11-14 Bone resorption under dentures can affect not only the alveolar bone but also. those found by a hand search of older references were also considered. the main feature of the “combination syndrome. there is continuous bone resorption under denture bases.21 Moreover. the continuous bone resorption stopped in the areas distal to the mandibular foramina after the patients had been provided with fixed prostheses supported by implants placed anterior to the foramina.26 The first group had no posterior teeth and no RPD. Only small and statistically insignificant changes in the bone height of the edentulous maxilla were found during a 5-year observation period in a patient group where the complete maxillary denture was opposed by a bar-retained mandibular RPD. there were considerable individual variations in the extent of the changes in all groups.”11 The initial prosthetic technique probably has no long-term influence on residual ridge resorption. primarily on the canines. In groups of patients who had been wearing complete mandibular dentures for different lengths of time. animal studies have shown that continuous pressure from an experimental denture caused bone resorption when exceeding a threshold value. a remodeling process of the alveolar bone occurs.18.

34 Some changes consistent with signs associated with combination syndrome 272 were noted33 but maxillary bone resorption was smaller compared with that reported by Kelly2 in the situation with remaining anterior teeth and a Class I mandibular RPD. and the study was not longitudinal. indicating that no conclusions can be drawn about the development of the noted “elongations. different percentages of maxillary anterior bone loss were noted. CARLSSON.30 “tuberosity elongation” was found in 5% of patients with complete dentures in both jaws. and they are not included in this review.34 Using panoramic radiographs. 1 group had a complete denture. It should be noted. Mandibular implant-supported or -retained prostheses.”30 All patients had a maxillary complete denture. as indicated by changes in measured masticatory forces. In another study of a group of patients with implantsupported overdentures in the mandible.” However. This might partly be explained by the small number of subjects in these 2 groups. and “posterior loss of occlusal contact were observed. Enlargement of the tuberosities In a study of denture patients treated at a dental school. but findings in patients at a dental school.37 However.36 The results showed a marked improvement in “chewing ability” after implant treatment. In fact. Jacobs et al35 followed up 3 groups of patients. AND OWALL nal study over 7 years found no significant difference in maxillary bone resorption in patients wearing a complete maxillary denture opposed by either a complete mandibular denture or natural teeth and a removable partial denture. In the mandible. In patients with bilaterally missing mandibular molars. However. However.38-40 Regarding changes of the edentulous maxilla in complete denture wearers. anterior bone loss in the maxilla. The groups were small.” VOLUME 90 NUMBER 3 . all with a complete maxillary denture.33.41-43 The relevance of these studies concerning bone resorption can be questioned. “tuberosity elongation” was found in 22% of those wearing a removable partial denture and in 56% of those with no RPD. The authors listed 5 changes “most consequential to denture wearing and most difficult to correct”: maxillary anterior bone loss. and hypermobile maxillary residual ridge. “Maxillary anterior alveolar bone loss” was nearly nonexistent in the group with complete mandibular dentures as well as in the group with natural dentition including bilateral molars. tuberosity enlargement. All of these changes were prevalent in less than 7% of the total sample but were found in 24% of the patients with a bilateral distal-extension RPD. According to the authors. No epidemiologic study of the combination syndrome was found. however. even if somewhat higher values were noted in the latter group. “loss of posterior occlusal contact” was also observed in these patients. mandibular posterior bone loss. the authors found no significant difference related to whether the patients wore an RPD or not. Further. however. The masticatory forces and deformation of the maxillary complete denture during function have been studied in patients with either a complete denture or a fixed implant-supported prosthesis in the mandible. An Australian implant center reported on anterior bone resorption beneath complete maxillary dentures when opposed by implant-supported mandibular prostheses.THE JOURNAL OF PROSTHETIC DENTISTRY ¨ PALMQVIST. another group an implant-retained overdenture. In groups with unilateral or bilateral missing molars.29 Examination records were reviewed in 150 consecutive denture patients at a dental school with regard to “prevalence of symptoms associated with combination syndrome. indicating an increase in denture deformation during function. Maxillary changes similar to the combination syndrome. and the criteria were not clarified to the readers.”31 The situation with a fixed implant-supported prosthesis in the mandible32 “did not appear to promote a condition similar to combination syndrome.31. the mandibular status differed. The anterior bone loss under a maxillary complete denture has also been studied when the mandibular overdenture was supported by a transmandibular implant with 4 posts penetrating the mandibular crest between the mental foramina. that this was not an epidemiologic study of a random sample. The most pronounced annual bone resorption in the maxilla was noted in the complete denture group and was statistically significant compared with the overdenture group. Bone resorption in the fixed implantsupported prosthesis group demonstrated values in between the other 2 groups that were not significantly different from the other groups. frequent midline fractures of the opposing maxillary complete denture was noted.32 The situation with a mandibular overdenture supported by 2 bar-connected implants resembled the situation with natural anterior teeth and an RPD. all variables presented in the article were dichotomous. no significantly increased levels of loading were measured by the strain gauges placed in the maxillary dentures. there are also several studies in which radiographs have not been used but measurements have been performed on casts. this finding has not been confirmed in more recent studies. and the third group had a fixed implant-supported prosthesis. The conclusion was that there should be no increased risk of failure or complications associated with loading clinically with the type of fixed implant-supported prostheses that were studied. maxillary alveolar ridge canting. the highest percentage of “maxillary anterior alveolar bone loss” (56%) was noted for the group wearing a Class I mandibular RPD. a possible explanation of these improved results could be that implants do not supra-erupt as natural teeth do.

20 This result has been confirmed in recent studies.53 A more extensive review up to the end of year 2000 identified 92 RCTs in prosthodontics. is that there seems to be no prospective study of the “combination syndrome” in spite of the fact that many people have been provided with a complete maxillary denture opposed by anterior mandibular teeth with or without a Class I mandibular RPD. prosthodontic journals showed that less than 2% of 3631 articles published over a 10-year period could be classified as RCTs.44.”44. as well as to changes in position of the anterior mandibular teeth.52 The supraeruption may create enlarged tuberosities without influence of a denture.30 However.45 No study was found focusing specifically on changes in the maxillary mucosa with respect to the mandibular dentition status.48 Kelly2 provided values for the resorption in the edentulous maxilla but not for the posterior. In situations where mandibular molars have been lost. It can be speculated that such changes in occlusion facilitate parafunctional activities such as clenching and thereby increase the pressure on the maxillary anterior alveolar bone. whereas no change of the bone level in the posterior region was noted for the group not wearing an RPD. AND OWALL THE JOURNAL OF PROSTHETIC DENTISTRY Papillary hyperplasia of the hard palate’s mucosa Epidemiologic studies of mucosal changes in denture wearers mostly report low percentage figures for “papillary hyperplasia of the hard palatal mucosa. “loss of bone from the anterior portion of the edentulous maxilla.21. A review of U.” Compared with the main feature.S. the longitudinal study over 25 years by Bergman et al49 provides no information on this point.” findings such as “papillary hyperplasia of the hard palatal mucosa” seem to be rare.¨ PALMQVIST. No other reports have been found regarding extrusion of mandibular anterior teeth in combination with a complete maxillary denture and a mandibular RPD.0 and 1. This speculative theory fits well with the result that patients who had been provided with Class I mandibular RPDs had development of more signs and symptoms of temporomandibular disorders over a 5-year period compared with a matched group of patients treated with cantilevered fixed partial dentures. edentulous parts of the mandible. he emphasized the negative role of the mandibular RPD.54 Perhaps somewhat more surprising. no randomized controlled trials (RCTs) on combination syndrome were found.” also called “papillomatous stomatitis. In the title of his article.” “Combination syndrome” is not included among hundreds of syndromes listed in the dictionary. However.”13 This does not mean that the observations made by Kelly2 were false. The same view was expressed by Keltjens et al.27 DISCUSSION Dorland’s Illustrated Medical Dictionary51 defines “syndrome” as “a set of symptoms which occur together. some even reporting bone apposition in the posterior areas when a fixed implant-supported prosthesis was used.5 mm.55 who found the traditional treatment for an edentulous maxilla opposed by a partially edentulous mandible with a complete denture and a Class I mandibular RPD to be “fundamentally inadequate.25. it may be indirectly concluded that there were considerable changes of the supporting tissues judging from the frequent relining of the RPDs during the first 10 years.26 In patients who received mandibular implant-supported fixed prostheses. Extrusion of mandibular anterior teeth Kelly demonstrated extrusion of the mandibular anterior teeth in all 6 patients with combination syndrome followed up for 3 years by means of profile radiographs. but none related to combination syndrome.2 The amount of extrusion varied between 1. Enlarged tuberosities are often seen together with supraerupted maxillary molars. loss of occlusal contacts can be attributed not only to bone resorption under mandibular distal extension bases but also to wear of the artificial denture teeth. Loss of established posterior occlusal contacts has been discussed as an important factor in relation to the combination syndrome. bone resorption in the posterior part of the mandible practically ceased. A study of patients with a complete maxillary denture opposed by a mandibular distal extension RPD retained by an anterior bar revealed more bone resorption in the posterior mandible than in the maxilla. a symptom complex. In a review of the literature. Not surprisingly.47-50 For example. A long-term 21-year study of patients wearing complete maxillary dentures provided no support for a systematic development of the “combination syndrome.” The authors also suggested use of implants for distal support. the authors have found no epidemiologic study of “combination syndrome.45 Enlarged tuberosities may also have other causes than those described by Kelly2 as part of the combination syndrome.56 It is also compatible with results from in vivo measurements showing that 273 . the sum of signs of any morbid state. the opposing maxillary molars may supraerupt together with the alveolar process.46 Most follow-up studies of removable partial dentures have not included measurement of bone resorption beneath the distal extension bases. From this review of the literature it seems obvious that SEPTEMBER 2003 “combination syndrome” does not meet the criteria to be included in such a list. CARLSSON. Bone resorption under mandibular RPD bases Continuous bone resorption in the mandible posterior to the remaining anterior teeth has been demonstrated in 2 groups of patients wearing different types of Class I mandibular RPDs.

Watson RM. J Prosthet Dent 1999. Aust Dent J 1969.59 indicating that missing posterior teeth should not necessarily be replaced. Tilvis R. Nevalainen JM. Desjardins RP. Glantz PO. A histomorphometric analysis on bone dynamics in denture supporting tissue under continuous pressure. 18.65 SUMMARY Bone resorption of the anterior part of the edentulous maxilla in association with remaining anterior mandibular teeth has been the subject of a limited number of studies of acceptable quality.14: 370-6. Carlsson GE. 21. Tallgren A. Sato T. Okamoto M. J Prosthet Dent 1979. 17.75:193-208. Acta Radiol 1964. Carlsson GE. Campbell RL. Crum RJ. Changes in height of the alveolar process in edentulous segments. The influence of wearing dentures on residual ridges: a comparative study. Chicago: Quintessence Publishing. 7. AND OWALL a fixed implant-supported prosthesis in the mandible opposing a complete maxillary denture improved the “chewing ability” but did not increase the levels of loads transferred to the denture base. On the basis of this review of the literature it may therefore be concluded that the “combination syndrome” does not meet the criteria to be accepted as a medical syndrome. A longitudinal. II. J Prosthet Dent 1970. 24. Rooney GE Jr. Haraldson T. Acta Odontol Scand 1997. Turner CR.53:56-61. Ragnarson N. J Oral Rehabil 1997. Bergman B. J Oral Rehabil 1980.2 Reviewed articles have shown greater bone loss in the mandible associated with an RPD compared with when no RPD or a fixed prostheses supported by anterior implants was provided.64.24:137-44. J Prosthet Dent 1985. 12.228 (Suppl):1-97. 20. Odontol Rev 1967. Effect of continuous pressure on histopathological changes in denture-supporting tissues. bilaterally missing mandibular posterior teeth) it seems reasonable to adopt the shortened dental arch concept. 8. 22. Mandibular bone resorption in patients treated with tissue-integrated prostheses and in complete-denture wearers.46 Compared with cantilevered fixed partial dentures. In: Turner CR. Astrand P. Carlsson GE. but the results have not been conclusive.24:37-46. CARLSSON. Changes caused by a mandibular removable partial denture opposing a maxillary complete denture. Hedegard B.55:306-13.40:610-3.57 The poor biologic outcome with Class I mandibular RPDs constitutes a strong indirect support for the “shortened dental arch” concept. Carlsson GE. Carlsson GE. The human dental mechanism. J Oral Rehabil 2002. Reduction of residual ridges: a major oral disease entity. Clinical morbidity and sequelae of treatment with complete dentures.27:120-32.41:124-8. more plaque and gingivitis. 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