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A prospective 10-year cephalometric follow-up study of patients with obstructive sleep apnea and snoring who used a mandibular protruding device
ORIGINAL ARTICLE
A prospective 10-year cephalometric follow-up study of patients with obstructive sleep apnea and snoring who used a mandibular protruding device € ran Isacssonc Anette M. C. Fransson,a,b Claudia Benavente-Lundahl,b and Go € Orebro and V€aster as, Sweden
Introduction: This 10-year prospective cephalometric study evaluates the influence of a mandibular protruding device (MPD) in people with obstructive sleep apnea and snoring. Methods: A baseline study population of 77 people was followed biennially. After 10 years, 65 people (45 MPD users and 20 stopped-MPD users) were reexamined. At baseline and after 10 years, a lateral cephalogram was taken in the upright position. Results: MPD users showed significant changes in all cephalometric variables except for maxillary protrusion. The maxillary incisors were retroclined by a mean –4.2 (standard deviation [SD] 3.95; P \0.001), mandibular incisors were proclined by a mean 3.2 (SD, 5.02; P \0.001), and SNB was reduced by a mean –0.6 (SD 1.41; P 5 0.01). In those who had stopped MPD use, these initial cephalometric values were retained. Significant changes in decreased overjet and overbite were seen in the MPD group but not in the MPD-stopped group. The length of the mandible (Cd-Pg) increased by a mean of 5.1 mm (SD 6.78; P \0.001) and 6.1 mm (SD 5.99; P \0.001) in MPD and MPD-stopped groups, respectively. The hyoid bone–mandibular plane distance (hy-ML) increased by a mean of 3.3 mm (SD, 2.90; P \0.001) and 3.8 mm (SD 3.67; P 5 0.001) in MPD and MPD-stopped groups, respectively. Conclusions: Long-term nocturnal MPD use causes retroclination of the maxillary incisors and proclination of the mandibular incisors with consequent decreased overjet and overbite. Both MPD and MPD-stopped users obtained increased mandibular length and lower position of the hyoid bone, which can be a normal physiological change with age. (Am J Orthod Dentofacial Orthop 2020;157:91-7)
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bstructive sleep apnea (OSA) is characterized by episodes of partial or total obstruction in the upper airways during sleep in combination with snoring and often daytime sleepiness and tiredness. € Department of Dental Research, Public Dental Service, Region Orebro County, € € and Faculty of Medicine and Health, Orebro University, Orebro, Sweden. b € Department of Orthodontics, Postgraduate Dental Education Center, Orebro, Sweden. c Department of Orofacial Pain and Jaw Function, V€astmanland Hospital, V€aster as, Sweden. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and none were reported. This research was supported by grants from Public Dental Health Service, Region € Orebro County, the Swedish Dental Society, the Uppsala-Orebro Regional Research Council, and Vastmanland County Council. No one from the study sponsors took part in the study design, collection, interpretation, or analysis of the data, writing the report, or the decision to submit the paper for publication. Address correspondence to: Anette M.C. Fransson, Department of Dental € Research, Public Dental Service, Region Orebro County, PO Box 1126, SE-701 € 11 Orebro, Sweden; e-mail, [email protected]. Submitted, September 2018; revised and accepted, February 2019. 0889-5406/$36.00 Ó 2019 by the American Association of Orthodontists. All rights reserved. https://doi.org/10.1016/j.ajodo.2019.02.018 a
The airway obstruction causes an arousal reaction with consequent sleep disturbance and impairment of sleep quality. The long-term medical consequences of untreated OSA are increased risk of developing high blood pressure, stroke, or heart failure.1-3 The first choice of treatment for severe OSA is continuous positive airway pressure (CPAP). A mandibular protruding device (MPD) that advances the mandible in a protruded position is an alternative treatment that opens the airway and thus avoids the collapse of the pharynx during sleep.4 Compliance is higher for an MPD than for CPAP.5 Although CPAP reduces the apnea-hypopnea index more than an MPD, Anandam et al6 found that both CPAP and MPD are equally effective therapies in reducing the risk of fatal cardiovascular events in patients with severe OSA. White et al7 compared CPAP and MPD after 1-month use and found that most patients preferred using an MPD (51%) to using a CPAP (21%); this finding is in agreement with earlier reports.5 Several different MPD designs are available commercially, and all seem to be associated with short- and 91
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long-term adverse experiences. The short-term adverse effects are complaints from the temporomandibular joint, jaw muscles, and teeth.8-12 Several articles have also reported on the long-term follow-up and have reported that forces from the MPD may cause proclination of the mandibular incisors and retroclination of the maxillary incisors, a well-known activator effect. Proclination of the mandibular incisors can cause an increase in lower face height and posterior rotation of the mandible.8,13-15 Follow-up reports of natural lifetime changes have shown that the dentoalveolar skeleton continues to change with time, as reflected in a natural mesial drift of the mandibular teeth even without MPD treatment.16 In a 2-year follow-up study with MPD treatment, Fransson et al8 found a significant change in the proclination of the mandibular incisors, retroclination of the maxillary incisors, increased anterior face height, and posterior rotation of the mandible. Later studies with a follow-up of 7 years confirmed the same observations.14,15,17 Most patients consider that the positive treatment effect of an MPD outweighs the adverse effects.18 There is limited evidence of the risk of developing pain and functional impairment after long-term use of an MPD. It is more common for people to discontinue use of an MPD because of a reduced effect on OSA symptoms rather than adverse events.12,19 The aim of this 10-year follow-up study of OSA and snoring patients was to use cephalometric measures to follow the dentofacial changes in association with the use of an MPD. MATERIAL AND METHODS
This prospective study examined observational effectiveness in people with OSA and snoring problems who were all treated with an MPD. Over 10 years, all patients still using their MPD were checked biennially, and the device was adjusted if needed. At the 10-year follow-up, all patients were re-called, including those who had stopped using their MPD. Upright lateral cephalograms were taken at the baseline and the 10-year follow-up. The baseline study population comprised 77 consecutive adult patients referred from the University Hospital for treatment at the Department of Stomatognathic € Physiology, Orebro University, with the diagnosis of OSA based on a polygraphic examination (oxygen desaturation index, $5) or snoring (oxygen desaturation index, \5). The inclusion criteria were a sufficient number of teeth to retain an MPD, good dental health, and a maximum protrusion range of $6 mm as measured with the George Gauge instrument (Boos Dental Laboratories, MN).20 The detailed patient eligibility and enrollment path have been previously described by.21 At the 10-
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Fig 1. The MPD covering all teeth was made of heatcured methyl methacrylate resin.
year follow-up, all baseline patients (except 3 who had died), including those who had stopped using their MPD, were re-called (n 5 74). All subjects signed an informed consent form after being informed about the purpose of the study. Approval for the main study was obtained from the Medical Ethics € Committee at Medical Centre Hospital, Orebro University. A second informed consent form was signed at the 10-year follow-up. For the 10-year follow-up, the application was approved by The Regional Ethical Review board, Uppsala, Sweden. MPDs were fabricated after the clinical examination. A George Gauge construction bite was used to advance the mandible $75% of the maximal protrusion and $5 mm from the retruded position. The MPD used in this study was a monobloc of heat-cured methyl methacrylate covering all the teeth with an opening in the frontal region (Fig 1). At the 10-year follow-up, the actual degree of mandibular advancement was measured with a steel ruler. At baseline and 10-year follow-up, a cephalogram was taken with the patient in the upright position with the teeth in intercuspation, the head supported by a cephalostat and orientated according to the Frankfort horizontal plane. The baseline analog cephalogram was obtained using a specially designed cephalostat equipped with an X-ray tube (Pantixhaube PH 125/80, Siemens, Stockholm, Sweden). The 10-year follow-up was made using a Cranex Tome Ceph digital unit (Soredex, Tuusula, Finland). The analog-to-digital transformation procedure was done by Depona AB (Vilhelmina, Sweden) to ensure high quality. The examination results were saved in Digital Imaging and Communications in Medicine format
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Fig 2. Flow diagram of the study participants.
and used in the FACAD analysis program (Ilexis AB, Link€ping, Sweden). A 12-bit gray scale (4096 shades) was o used to optimize the quality. The cephalograms were calibrated before the analyses based on the distance C2 to C3 measured in millimeters on the analog cephalogram and calibrated in FACAD on the digitized cephalogram. The following measures were included in the cephalometric analyses: hyoid position, incisor inclination, overjet, overbite, jaw position to the skull base, and skeletal measures such as the mandible length. All cephalometric measurements and analyses were performed by the same examiner (CBL) who was blinded to the continued or stopped use of the MPD. The examiner's consistency was evaluated by rereading 20 randomly selected cephalograms obtained at both the baseline and 10-year follow-up. The measurements were repeated after $1 month. A maximum of 10 cephalograms was analyzed at a time to avoid operator fatigue. Test-retest reliability was calculated using the intraclass correlation coefficient (ICC) using IBM SPSS Statistics, version 21 (IBM Corp, Armonk, NY). Statistical analysis
No power calculation was made because of the structure of the study. The size of the sample was chosen to be able to describe effectiveness following long-term use of an MPD in a typical OSA population. Descriptive
statistics are used to delineate the baseline patient characteristics. Changes from the baseline to the 10-year follow-up were analyzed using a paired Student t test for continuous data, and P \0.05 was considered to be significant. RESULTS
At the 10-year follow-up, 65 patients were available for analysis: 45 were MPD users (30 with OSA and 15 snorers; Fig 2), and 20 had stopped using the MPD (12 primarily with OSA and 8 were snorers; Fig 2). The patients' baseline characteristics are described in Table I. In the reference group of MPD-stopped users, 14 patients stopped using the MPD after 4 years, 2 patients stopped after 6 years, and 4 patients stopped after 8 years. The mean advancement with MPD at the 10-year follow-up was 6.5 mm (range, 2.0-10.5), but from the baseline situation, it was impossible to determine the advancement precisely, because of the mesial drift of the mandibular teeth during the 10 years. The measured cephalogram overjet changed by a mean –1.5 mm, (standard deviation [SD], 1.89; P \0.001) and 0.2 mm (SD, 0.85, P 5 0.24), and overbite changed by a mean –0.7 mm (SD, 1.41; P 5 0.002) and 0.4 mm (SD, 1.19; P 5 0.18) in the MPD and MPDstopped groups, respectively.
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Table I. Baseline demographics describing age, sex, body mass index, and neck size for MPD users and MPD-stopped
patients MPD users
Age (y) Mean (SD) Range BMI (kg/m2) Mean (SD) Range Neck size (cm) Mean (SD) Range
Patients who stopped using the MPD
Men (n 5 35)
Women (n 5 10)
Total (n 5 45)
Men (n 5 17)
Women (n 5 3)
Total (n 5 20)
54 (8.3) 37-73
54 (7.1) 42-61
54 (8.0) 37-73
52 (7.2) 39-65
62 (4.6) 57-66
54 (7.7) 39-66
29 (3.8) 21-36
31 (3.8) 26-36
29 (3.8) 21-36
30 (3.0) 25-38
29 (2.5) 26-31
30 (2.9) 25-38
42.1 (2.7) 37-49
38.9 (1.9) 36-41
41.4 (2.9) 36-49
43.1 (2.9) 39-51.5
36.3 (2.1) 34-38
42.1 (3.7) 34-51.5
BMI, body mass index.
Table II. Angular and linear cephalometric measurements at the baseline and at the 10-year follow-up in MPD users Baseline SNA (o) SNB (o) ILs/SN (o) ILi/ML (o) Cd-Pg (mm) hy-ML (mm)
n 45 45 45 45 45 39
Mean 82.9 79.6 100.9 93.1 108.0 18.9
10-year follow-up SD 3.7 3.8 8.5 9.4 8.7 4.2
Mean diff 0.1 –0.6 –4.2 3.2 5.1 3.3
SDd 1.1 1.4 4.0 5.0 6.8 2.9
95% CId –0.3 to 0.4 –1.0 to –0.1 –5.3 to –3.0 1.7-4.7 3.1-7.1 2.3-4.2
P* ns 0.010 \0.001 \0.001 \0.001 \0.001
SDd, standard deviation of the difference; CId, confidence interval of difference of means; SNA, horizontal relation of the maxilla to skull base; ns, not significant; SNB, horizontal relation of the mandible to skull base; ILs/SN, angle of inclination of the maxillary incisors with sella-nasion line; ILi/ML, angle of inclination of the mandibular incisors with mandibular line; Cd-Pg, mandibular length condylion to pogonion; hy-ML, perpendicular distance from the mandibular line to hyoid. *Paired Student t test.
Intraexaminer reliability for the analysis of the cephalograms showing the angles and dental and skeletal distances at the baseline and 10-year follow-up confirmed the highly significant agreement. The ICC values ranged from 0.90 to 0.98 for the baseline values and from 0.87 to 0.97 for the 10-year follow-up values. An ICC value .0.75 indicates excellent reliability. At the 10-year follow-up, the hyoid was missing on the cephalogram in 6 MPD users and 3 MPD-stopped users. Consequently, the variable hyoid bone– mandibular plane distance (hy-ML) was available for 39 and 17 patients, respectively. The position of the maxilla in relation to the skull base (SNA angle) did not change significantly over time in either group. The mandible in relation to the skull base (SNB angle) was reduced in the MPD users by a mean –0.6 (standard deviation of the difference [SDd], 1.4; P 5 0.010), which indicated posterior rotation. The SNB angle did not change in the MPD-stopped group (P 5 not significant). The maxillary incisors were significantly retroclined among the MPD users; that is, the ILs/SN showed a
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mean change of –4.2 (SDd, 4.0; P \0.001) but did not change in the MPD-stopped group (Tables II and III). The mandibular incisors were significantly proclined in the MPD group; that is, ILi/ML showed a mean change of 3.2 (SDd, 5.0; P \0.001) but did not change in the MPD-stopped group (Tables II and III). The mandibular length (Cd-Pg) and the hyoid position to the mandibular plane (hy-ML) increased significantly in both groups (Tables II and III). Figure 3 shows a cephalometric tracing from a subject that is representative of the study's main findings. DISCUSSION
This prospective 10-year follow-up study of patients with OSA or snoring describes the dentoskeletal changes following treatment with a monobloc MPD. The cephalometric analysis showed significant retroclination of the maxillary incisors as well as the proclination of the mandibular incisors among those who continued using the appliance. By contrast, the MPD-stopped group
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Table III. Angular and linear cephalometric measurements at baseline and at the 10-year follow-up in patients who
stopped using the MPD Baseline SNA ( ) SNB ( ) ILs/SN ( ) ILi/ML ( ) Cd-Pg (mm) hy-ML (mm)
n 20 20 20 20 20 17
Mean 83.5 80.5 97.8 88.8 106.5 20.2
10-year follow-up SD 2.9 3.8 9.2 6.8 8.0 4.4
Mean diff –0.4 –0.9 –0.6 1.1 6.1 3.8
SDd 3.2 2.6 3.2 4.4 6.0 3.7
95% CId –1.9 to 1.1 –2.1 to 0.3 –2.1 to 1.0 –1.0 to 3.2 3.3-8.9 1.9-5.7
P* ns ns ns ns \0.001 0.001
SDd, standard deviation of the difference; CId, confidence interval of difference of means; SNA, horizontal relation of the maxilla to skull base; ns, not significant; SNB, horizontal relation of the mandible to skull base; ILs/SN, angle of inclination of the maxillary incisors with sella-nasion line; ILi/ML, angle of inclination of the mandibular incisors with mandibular line; Cd-Pg, mandibular length condylion to pogonion; hy-ML, perpendicular distance from the mandibular line to hyoid. *Paired Student t test.
Fig 3. An example of one MPD user representing the main findings of the study. Superimposed cephalometric tracings describing the jaw relationship, incisor angulation, and hyoid position of an MPD user at baseline (black lines) and at the 10-year follow-up (red lines) are shown.
showed minor nonsignificant changes in incisor angulation. Our results are consistent with those of several previous studies.8,10,13,14,17,21,22 The consequence of the changed incisor angulation is that both the overjet and overbite decreased. These findings are consistent when measured clinically on
dental casts and cephalograms,23 and our study confirms these earlier findings. In a review article, Hoffstein9 summarized 11 studies with a total of 389 patients and found similar results, such as mean reductions in overbite of –1.3 mm and overjet of –1.4 mm. Almeida et al14 reported similar results in a long-term followup study that showed dental but not craniofacial skeletal changes. They also concluded that the changes would continue with increasing time using an MPD. Alessandri-Bonetti et al24 concluded that the overbite decreases provided the treatment is ongoing but that the mandibular incisor inclination changes less over time. In a study of dental casts, Pliska et al25 found that overbite and mandibular intermolar distance decreased less over time, whereas overjet, mandibular intercanine distance, and lower arch crowding all decreased continuously at a constant rate. In a recent meta-analysis of studies with a treatment duration ranging from mean 6 months to 11 years, Araie et al21 found that the changes became larger over time. Alessandri-Bonetti et al24 assumed that the use of an MPD causes the jaw muscles to extend, which creates a posterior force that pushes the mandible backward during MPD treatment, and transmits a posterior force to the maxillary incisors with a consequent inclination. The authors concluded that the mandible attempts to return to its natural position and thereby transmits an anteriorly directed force against the mandibular incisors, which then procline. The meta-analysis by Araie et al21 found a small nonsignificant decrease in the SNA and SNB angles, which indicated downward rotation of the mandible. We also observed this phenomenon. As shown in our study, stopping MPD therapy may normalize or prevent further skeletal changes. However, a 32-year follow-up study of facial skeletal growth after adolescent Herbst
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therapy of malocclusion reported continuous forward growth of both the mandible and maxilla.26 During that period, mean forward mandibular growth of 8.9 mm and maxillary growth of 6.1 mm were registered. Whether this also applies to people not subjected to orthodontic treatment remains to be investigated. Dager et al16 concluded that dental arches continue to change throughout adulthood. When investigating skeletal changes following MPD treatment, an untreated reference material should be included for comparison to determine whether the side effects are caused by the device. We did not include such a reference group, and the small sample of the stopped-MPD group in our study provides only a weak indicator that an MPD contributes to the occlusal and skeletal changes. Previous studies claim that the amount of MPDguided protrusion is an essential contributor to adverse events.27 Doff et al28 found an association between a decrease in overbite and the degree of mandibular advancement attributed to an MPD. The mean mandibular advancement with the MPD at the 10-year followup in our study was 6.5 mm, which was identical to the baseline advancement for the entire group29, even though all patients were offered to change their MPDs if needed during the 10 years. These data suggest that the degree of protrusion with an MPD over time can be affected by the mesial drift and would probably be more significant after 10 years. A shortcoming of our study was the use of analog cephalograms at the baseline and a digitalized technique at the 10-year follow-up. Although we corrected for the difference in the magnification factor between the 2 techniques, a systematic error may have been introduced. The test-retest reliability was excellent and the angle measures appeared to be more robust than the measures of distance; consequently, the values for the length of the mandible and hyoid position must be interpreted cautiously. From the long-term perspective, 80%-90% of MPD users exhibit occlusal changes, half of them with favorable changes. Class II Division 1 gets less horizontal overjet and vertical overbite. The other half develop unfavorable changes, Class I involving a frontal edge-toedge situation and Class III involving an even further advanced mandible.14,15 The anterior shift of the mandible may be associated with a posterior open bite; whereas, other shifts retain posterior contacts but are associated with an altered occlusion.14 Bondemark et al13 published a pilot study that reported an increased mandibular length (Cd-Pg) after 2 years of using an MPD. We did not confirm this finding in our 2-year follow-up.8 However, at the 10-year
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follow-up, the mandibular length and the hyoid position to the mandibular line increased significantly, regardless of the use of an MPD. This phenomenon may reflect a physiological change, or it might have been a technical misinterpretation of the digitalization of the baseline analog cephalograms. From a statistical perspective the sample is limited, and the SD at many measures is large, and consequently the P values should be interpreted cautiously. CONCLUSIONS
Long-term nocturnal use of an MPD caused retroclination of the maxillary incisors and proclination of the mandibular incisors with consequent decreased overjet and overbite. Both MPD users and MPD-stopped users obtained increased mandibular length and lower position of the hyoid bone which can be a normal physiological change with age. ACKNOWLEDGMENTS
The authors thank the Department of Oral Radiology, € € Public Dental Service, Region Orebro County, Orebro, Sweden for the radiological support.
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9. Hoffstein V. Review of oral appliances for treatment of sleepdisordered breathing. Sleep Breath 2007;11:1-22. 10. Rose EC, Staats R, Virchow C Jr, Jonas IE. Occlusal and skeletal effects of an oral appliance in the treatment of obstructive sleep apnea. Chest 2002;122:871-7. 11. Isacsson G, Nohlert E, Fransson AMC, Bornefalk-Hermansson A, Wiman Eriksson E, Ortlieb E, et al. Use of bibloc and monobloc oral appliances in obstructive sleep apnoea: a multicentre, randomized, blinded, parallel-group equivalence trial. Eur J Orthod 2019;41:80-8. 12. Lim J, Lasserson TJ, Fleetham J, Wright J. Oral appliances for obstructive sleep apnoea. Cochrane Database Syst Rev 2006; CD004435. 13. Bondemark L. Does 2 years' nocturnal treatment with a mandibular advancement splint in adult patients with snoring and OSAS cause a change in the posture of the mandible? Am J Orthod Dentofacial Orthop 1999;116:621-8. 14. Almeida FR, Lowe AA, Sung JO, Tsuiki S, Otsuka R. Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: part 1. Cephalometric analysis. Am J Orthod Dentofacial Orthop 2006;129:195-204. 15. Doff MH, Hoekema A, Pruim GJ, Huddleston Slater JJ, Stegenga B. Long-term oral-appliance therapy in obstructive sleep apnea: a cephalometric study of craniofacial changes. J Dent 2010;38:1010-8. 16. Dager MM, McNamara JA, Baccetti T, Franchi L. Aging in the craniofacial complex. Angle Orthod 2008;78:440-4. 17. Wang X, Gong X, Yu Z, Gao X, Zhao Y. Follow-up study of dental and skeletal changes in patients with obstructive sleep apnea and hypopnea syndrome with long-term treatment with the Silensor appliance. Am J Orthod Dentofacial Orthop 2015;147:559-65. 18. Fransson AM, Tegelberg A, Johansson A, Wenneberg B. Influence on the masticatory system in treatment of obstructive sleep apnea and snoring with a mandibular protruding device: a 2-year followup. Am J Orthod Dentofacial Orthop 2004;126:687-93. 19. Fransson AM, Tegelberg A, Leissner L, Wenneberg B, Isacsson G. Effects of a mandibular protruding device on the sleep of patients with obstructive sleep apnea and snoring problems: a 2-year follow-up. Sleep Breath 2003;7:131-41.
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20. George PT. A new instrument for functional appliance bite registration. J Clin Orthod 1992;26:721-3. 21. Araie T, Okuno K, Ono Minagi H, Sakai T. Dental and skeletal changes associated with long-term oral appliance use for obstructive sleep apnea: A systematic review and meta-analysis. Sleep Med Rev 2018;41:161-72. 22. Doff MH, Finnema KJ, Hoekema A, Wijkstra PJ, de Bont LG, Stegenga B. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on dental side effects. Clin Oral Investig 2013;17:475-82. 23. Fransson AMC, Kowalczyk A, Isacsson G. A prospective 10-year follow-up dental cast study of patients with obstructive sleep apnoea/snoring who use a mandibular protruding device. Eur J Orthod 2017;39:502-8. 24. Alessandri-Bonetti G, D’Anto V, Stipa C, Rongo R, IncertiParenti S, Michelotti A. Dentoskeletal effects of oral appliance wear in obstructive sleep apnoea and snoring patients. Eur J Orthod 2017;39:482-8. 25. Pliska BT, Nam H, Chen H, Lowe AA, Almeida FR. Obstructive sleep apnea and mandibular advancement splints: occlusal effects and progression of changes associated with a decade of treatment. J Clin Sleep Med 2014;10:1285-91. 26. Pancherz H, Bjerklin K, Hashemi K. Late adult skeletofacial growth after adolescent Herbst therapy: a 32-year longitudinal follow-up study. Am J Orthod Dentofacial Orthop 2015;147: 19-28. 27. Marklund M, Franklin KA, Persson M. Orthodontic side-effects of mandibular advancement devices during treatment of snoring and sleep apnoea. Eur J Orthod 2001;23:135-44. 28. Doff MH, Veldhuis SK, Hoekema A, Slater JJ, Wijkstra PJ, de Bont LG, et al. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on temporomandibular side effects. Clin Oral Investig 2012;16:689-97. 29. Fransson AM, Tegelberg A, Svenson BA, Wenneberg B, Isacsson G. Validation of measurements of mandibular protrusion in the treatment of obstructive sleep apnoea and snoring with a mandibular protruding device. Eur J Orthod 2003;25:377-83.
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A prospective 10-year cephalometric follow-up study of patients with obstructive sleep apnea and snoring who used a mandibular protruding device € ran Isacssonc Anette M. C. Fransson,a,b Claudia Benavente-Lundahl,b and Go € Orebro and V€aster as, Sweden
Introduction: This 10-year prospective cephalometric study evaluates the influence of a mandibular protruding device (MPD) in people with obstructive sleep apnea and snoring. Methods: A baseline study population of 77 people was followed biennially. After 10 years, 65 people (45 MPD users and 20 stopped-MPD users) were reexamined. At baseline and after 10 years, a lateral cephalogram was taken in the upright position. Results: MPD users showed significant changes in all cephalometric variables except for maxillary protrusion. The maxillary incisors were retroclined by a mean –4.2 (standard deviation [SD] 3.95; P \0.001), mandibular incisors were proclined by a mean 3.2 (SD, 5.02; P \0.001), and SNB was reduced by a mean –0.6 (SD 1.41; P 5 0.01). In those who had stopped MPD use, these initial cephalometric values were retained. Significant changes in decreased overjet and overbite were seen in the MPD group but not in the MPD-stopped group. The length of the mandible (Cd-Pg) increased by a mean of 5.1 mm (SD 6.78; P \0.001) and 6.1 mm (SD 5.99; P \0.001) in MPD and MPD-stopped groups, respectively. The hyoid bone–mandibular plane distance (hy-ML) increased by a mean of 3.3 mm (SD, 2.90; P \0.001) and 3.8 mm (SD 3.67; P 5 0.001) in MPD and MPD-stopped groups, respectively. Conclusions: Long-term nocturnal MPD use causes retroclination of the maxillary incisors and proclination of the mandibular incisors with consequent decreased overjet and overbite. Both MPD and MPD-stopped users obtained increased mandibular length and lower position of the hyoid bone, which can be a normal physiological change with age. (Am J Orthod Dentofacial Orthop 2020;157:91-7)
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bstructive sleep apnea (OSA) is characterized by episodes of partial or total obstruction in the upper airways during sleep in combination with snoring and often daytime sleepiness and tiredness. € Department of Dental Research, Public Dental Service, Region Orebro County, € € and Faculty of Medicine and Health, Orebro University, Orebro, Sweden. b € Department of Orthodontics, Postgraduate Dental Education Center, Orebro, Sweden. c Department of Orofacial Pain and Jaw Function, V€astmanland Hospital, V€aster as, Sweden. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and none were reported. This research was supported by grants from Public Dental Health Service, Region € Orebro County, the Swedish Dental Society, the Uppsala-Orebro Regional Research Council, and Vastmanland County Council. No one from the study sponsors took part in the study design, collection, interpretation, or analysis of the data, writing the report, or the decision to submit the paper for publication. Address correspondence to: Anette M.C. Fransson, Department of Dental € Research, Public Dental Service, Region Orebro County, PO Box 1126, SE-701 € 11 Orebro, Sweden; e-mail, [email protected]. Submitted, September 2018; revised and accepted, February 2019. 0889-5406/$36.00 Ó 2019 by the American Association of Orthodontists. All rights reserved. https://doi.org/10.1016/j.ajodo.2019.02.018 a
The airway obstruction causes an arousal reaction with consequent sleep disturbance and impairment of sleep quality. The long-term medical consequences of untreated OSA are increased risk of developing high blood pressure, stroke, or heart failure.1-3 The first choice of treatment for severe OSA is continuous positive airway pressure (CPAP). A mandibular protruding device (MPD) that advances the mandible in a protruded position is an alternative treatment that opens the airway and thus avoids the collapse of the pharynx during sleep.4 Compliance is higher for an MPD than for CPAP.5 Although CPAP reduces the apnea-hypopnea index more than an MPD, Anandam et al6 found that both CPAP and MPD are equally effective therapies in reducing the risk of fatal cardiovascular events in patients with severe OSA. White et al7 compared CPAP and MPD after 1-month use and found that most patients preferred using an MPD (51%) to using a CPAP (21%); this finding is in agreement with earlier reports.5 Several different MPD designs are available commercially, and all seem to be associated with short- and 91
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long-term adverse experiences. The short-term adverse effects are complaints from the temporomandibular joint, jaw muscles, and teeth.8-12 Several articles have also reported on the long-term follow-up and have reported that forces from the MPD may cause proclination of the mandibular incisors and retroclination of the maxillary incisors, a well-known activator effect. Proclination of the mandibular incisors can cause an increase in lower face height and posterior rotation of the mandible.8,13-15 Follow-up reports of natural lifetime changes have shown that the dentoalveolar skeleton continues to change with time, as reflected in a natural mesial drift of the mandibular teeth even without MPD treatment.16 In a 2-year follow-up study with MPD treatment, Fransson et al8 found a significant change in the proclination of the mandibular incisors, retroclination of the maxillary incisors, increased anterior face height, and posterior rotation of the mandible. Later studies with a follow-up of 7 years confirmed the same observations.14,15,17 Most patients consider that the positive treatment effect of an MPD outweighs the adverse effects.18 There is limited evidence of the risk of developing pain and functional impairment after long-term use of an MPD. It is more common for people to discontinue use of an MPD because of a reduced effect on OSA symptoms rather than adverse events.12,19 The aim of this 10-year follow-up study of OSA and snoring patients was to use cephalometric measures to follow the dentofacial changes in association with the use of an MPD. MATERIAL AND METHODS
This prospective study examined observational effectiveness in people with OSA and snoring problems who were all treated with an MPD. Over 10 years, all patients still using their MPD were checked biennially, and the device was adjusted if needed. At the 10-year follow-up, all patients were re-called, including those who had stopped using their MPD. Upright lateral cephalograms were taken at the baseline and the 10-year follow-up. The baseline study population comprised 77 consecutive adult patients referred from the University Hospital for treatment at the Department of Stomatognathic € Physiology, Orebro University, with the diagnosis of OSA based on a polygraphic examination (oxygen desaturation index, $5) or snoring (oxygen desaturation index, \5). The inclusion criteria were a sufficient number of teeth to retain an MPD, good dental health, and a maximum protrusion range of $6 mm as measured with the George Gauge instrument (Boos Dental Laboratories, MN).20 The detailed patient eligibility and enrollment path have been previously described by.21 At the 10-
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Fig 1. The MPD covering all teeth was made of heatcured methyl methacrylate resin.
year follow-up, all baseline patients (except 3 who had died), including those who had stopped using their MPD, were re-called (n 5 74). All subjects signed an informed consent form after being informed about the purpose of the study. Approval for the main study was obtained from the Medical Ethics € Committee at Medical Centre Hospital, Orebro University. A second informed consent form was signed at the 10-year follow-up. For the 10-year follow-up, the application was approved by The Regional Ethical Review board, Uppsala, Sweden. MPDs were fabricated after the clinical examination. A George Gauge construction bite was used to advance the mandible $75% of the maximal protrusion and $5 mm from the retruded position. The MPD used in this study was a monobloc of heat-cured methyl methacrylate covering all the teeth with an opening in the frontal region (Fig 1). At the 10-year follow-up, the actual degree of mandibular advancement was measured with a steel ruler. At baseline and 10-year follow-up, a cephalogram was taken with the patient in the upright position with the teeth in intercuspation, the head supported by a cephalostat and orientated according to the Frankfort horizontal plane. The baseline analog cephalogram was obtained using a specially designed cephalostat equipped with an X-ray tube (Pantixhaube PH 125/80, Siemens, Stockholm, Sweden). The 10-year follow-up was made using a Cranex Tome Ceph digital unit (Soredex, Tuusula, Finland). The analog-to-digital transformation procedure was done by Depona AB (Vilhelmina, Sweden) to ensure high quality. The examination results were saved in Digital Imaging and Communications in Medicine format
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Fig 2. Flow diagram of the study participants.
and used in the FACAD analysis program (Ilexis AB, Link€ping, Sweden). A 12-bit gray scale (4096 shades) was o used to optimize the quality. The cephalograms were calibrated before the analyses based on the distance C2 to C3 measured in millimeters on the analog cephalogram and calibrated in FACAD on the digitized cephalogram. The following measures were included in the cephalometric analyses: hyoid position, incisor inclination, overjet, overbite, jaw position to the skull base, and skeletal measures such as the mandible length. All cephalometric measurements and analyses were performed by the same examiner (CBL) who was blinded to the continued or stopped use of the MPD. The examiner's consistency was evaluated by rereading 20 randomly selected cephalograms obtained at both the baseline and 10-year follow-up. The measurements were repeated after $1 month. A maximum of 10 cephalograms was analyzed at a time to avoid operator fatigue. Test-retest reliability was calculated using the intraclass correlation coefficient (ICC) using IBM SPSS Statistics, version 21 (IBM Corp, Armonk, NY). Statistical analysis
No power calculation was made because of the structure of the study. The size of the sample was chosen to be able to describe effectiveness following long-term use of an MPD in a typical OSA population. Descriptive
statistics are used to delineate the baseline patient characteristics. Changes from the baseline to the 10-year follow-up were analyzed using a paired Student t test for continuous data, and P \0.05 was considered to be significant. RESULTS
At the 10-year follow-up, 65 patients were available for analysis: 45 were MPD users (30 with OSA and 15 snorers; Fig 2), and 20 had stopped using the MPD (12 primarily with OSA and 8 were snorers; Fig 2). The patients' baseline characteristics are described in Table I. In the reference group of MPD-stopped users, 14 patients stopped using the MPD after 4 years, 2 patients stopped after 6 years, and 4 patients stopped after 8 years. The mean advancement with MPD at the 10-year follow-up was 6.5 mm (range, 2.0-10.5), but from the baseline situation, it was impossible to determine the advancement precisely, because of the mesial drift of the mandibular teeth during the 10 years. The measured cephalogram overjet changed by a mean –1.5 mm, (standard deviation [SD], 1.89; P \0.001) and 0.2 mm (SD, 0.85, P 5 0.24), and overbite changed by a mean –0.7 mm (SD, 1.41; P 5 0.002) and 0.4 mm (SD, 1.19; P 5 0.18) in the MPD and MPDstopped groups, respectively.
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Table I. Baseline demographics describing age, sex, body mass index, and neck size for MPD users and MPD-stopped
patients MPD users
Age (y) Mean (SD) Range BMI (kg/m2) Mean (SD) Range Neck size (cm) Mean (SD) Range
Patients who stopped using the MPD
Men (n 5 35)
Women (n 5 10)
Total (n 5 45)
Men (n 5 17)
Women (n 5 3)
Total (n 5 20)
54 (8.3) 37-73
54 (7.1) 42-61
54 (8.0) 37-73
52 (7.2) 39-65
62 (4.6) 57-66
54 (7.7) 39-66
29 (3.8) 21-36
31 (3.8) 26-36
29 (3.8) 21-36
30 (3.0) 25-38
29 (2.5) 26-31
30 (2.9) 25-38
42.1 (2.7) 37-49
38.9 (1.9) 36-41
41.4 (2.9) 36-49
43.1 (2.9) 39-51.5
36.3 (2.1) 34-38
42.1 (3.7) 34-51.5
BMI, body mass index.
Table II. Angular and linear cephalometric measurements at the baseline and at the 10-year follow-up in MPD users Baseline SNA (o) SNB (o) ILs/SN (o) ILi/ML (o) Cd-Pg (mm) hy-ML (mm)
n 45 45 45 45 45 39
Mean 82.9 79.6 100.9 93.1 108.0 18.9
10-year follow-up SD 3.7 3.8 8.5 9.4 8.7 4.2
Mean diff 0.1 –0.6 –4.2 3.2 5.1 3.3
SDd 1.1 1.4 4.0 5.0 6.8 2.9
95% CId –0.3 to 0.4 –1.0 to –0.1 –5.3 to –3.0 1.7-4.7 3.1-7.1 2.3-4.2
P* ns 0.010 \0.001 \0.001 \0.001 \0.001
SDd, standard deviation of the difference; CId, confidence interval of difference of means; SNA, horizontal relation of the maxilla to skull base; ns, not significant; SNB, horizontal relation of the mandible to skull base; ILs/SN, angle of inclination of the maxillary incisors with sella-nasion line; ILi/ML, angle of inclination of the mandibular incisors with mandibular line; Cd-Pg, mandibular length condylion to pogonion; hy-ML, perpendicular distance from the mandibular line to hyoid. *Paired Student t test.
Intraexaminer reliability for the analysis of the cephalograms showing the angles and dental and skeletal distances at the baseline and 10-year follow-up confirmed the highly significant agreement. The ICC values ranged from 0.90 to 0.98 for the baseline values and from 0.87 to 0.97 for the 10-year follow-up values. An ICC value .0.75 indicates excellent reliability. At the 10-year follow-up, the hyoid was missing on the cephalogram in 6 MPD users and 3 MPD-stopped users. Consequently, the variable hyoid bone– mandibular plane distance (hy-ML) was available for 39 and 17 patients, respectively. The position of the maxilla in relation to the skull base (SNA angle) did not change significantly over time in either group. The mandible in relation to the skull base (SNB angle) was reduced in the MPD users by a mean –0.6 (standard deviation of the difference [SDd], 1.4; P 5 0.010), which indicated posterior rotation. The SNB angle did not change in the MPD-stopped group (P 5 not significant). The maxillary incisors were significantly retroclined among the MPD users; that is, the ILs/SN showed a
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mean change of –4.2 (SDd, 4.0; P \0.001) but did not change in the MPD-stopped group (Tables II and III). The mandibular incisors were significantly proclined in the MPD group; that is, ILi/ML showed a mean change of 3.2 (SDd, 5.0; P \0.001) but did not change in the MPD-stopped group (Tables II and III). The mandibular length (Cd-Pg) and the hyoid position to the mandibular plane (hy-ML) increased significantly in both groups (Tables II and III). Figure 3 shows a cephalometric tracing from a subject that is representative of the study's main findings. DISCUSSION
This prospective 10-year follow-up study of patients with OSA or snoring describes the dentoskeletal changes following treatment with a monobloc MPD. The cephalometric analysis showed significant retroclination of the maxillary incisors as well as the proclination of the mandibular incisors among those who continued using the appliance. By contrast, the MPD-stopped group
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Table III. Angular and linear cephalometric measurements at baseline and at the 10-year follow-up in patients who
stopped using the MPD Baseline SNA ( ) SNB ( ) ILs/SN ( ) ILi/ML ( ) Cd-Pg (mm) hy-ML (mm)
n 20 20 20 20 20 17
Mean 83.5 80.5 97.8 88.8 106.5 20.2
10-year follow-up SD 2.9 3.8 9.2 6.8 8.0 4.4
Mean diff –0.4 –0.9 –0.6 1.1 6.1 3.8
SDd 3.2 2.6 3.2 4.4 6.0 3.7
95% CId –1.9 to 1.1 –2.1 to 0.3 –2.1 to 1.0 –1.0 to 3.2 3.3-8.9 1.9-5.7
P* ns ns ns ns \0.001 0.001
SDd, standard deviation of the difference; CId, confidence interval of difference of means; SNA, horizontal relation of the maxilla to skull base; ns, not significant; SNB, horizontal relation of the mandible to skull base; ILs/SN, angle of inclination of the maxillary incisors with sella-nasion line; ILi/ML, angle of inclination of the mandibular incisors with mandibular line; Cd-Pg, mandibular length condylion to pogonion; hy-ML, perpendicular distance from the mandibular line to hyoid. *Paired Student t test.
Fig 3. An example of one MPD user representing the main findings of the study. Superimposed cephalometric tracings describing the jaw relationship, incisor angulation, and hyoid position of an MPD user at baseline (black lines) and at the 10-year follow-up (red lines) are shown.
showed minor nonsignificant changes in incisor angulation. Our results are consistent with those of several previous studies.8,10,13,14,17,21,22 The consequence of the changed incisor angulation is that both the overjet and overbite decreased. These findings are consistent when measured clinically on
dental casts and cephalograms,23 and our study confirms these earlier findings. In a review article, Hoffstein9 summarized 11 studies with a total of 389 patients and found similar results, such as mean reductions in overbite of –1.3 mm and overjet of –1.4 mm. Almeida et al14 reported similar results in a long-term followup study that showed dental but not craniofacial skeletal changes. They also concluded that the changes would continue with increasing time using an MPD. Alessandri-Bonetti et al24 concluded that the overbite decreases provided the treatment is ongoing but that the mandibular incisor inclination changes less over time. In a study of dental casts, Pliska et al25 found that overbite and mandibular intermolar distance decreased less over time, whereas overjet, mandibular intercanine distance, and lower arch crowding all decreased continuously at a constant rate. In a recent meta-analysis of studies with a treatment duration ranging from mean 6 months to 11 years, Araie et al21 found that the changes became larger over time. Alessandri-Bonetti et al24 assumed that the use of an MPD causes the jaw muscles to extend, which creates a posterior force that pushes the mandible backward during MPD treatment, and transmits a posterior force to the maxillary incisors with a consequent inclination. The authors concluded that the mandible attempts to return to its natural position and thereby transmits an anteriorly directed force against the mandibular incisors, which then procline. The meta-analysis by Araie et al21 found a small nonsignificant decrease in the SNA and SNB angles, which indicated downward rotation of the mandible. We also observed this phenomenon. As shown in our study, stopping MPD therapy may normalize or prevent further skeletal changes. However, a 32-year follow-up study of facial skeletal growth after adolescent Herbst
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therapy of malocclusion reported continuous forward growth of both the mandible and maxilla.26 During that period, mean forward mandibular growth of 8.9 mm and maxillary growth of 6.1 mm were registered. Whether this also applies to people not subjected to orthodontic treatment remains to be investigated. Dager et al16 concluded that dental arches continue to change throughout adulthood. When investigating skeletal changes following MPD treatment, an untreated reference material should be included for comparison to determine whether the side effects are caused by the device. We did not include such a reference group, and the small sample of the stopped-MPD group in our study provides only a weak indicator that an MPD contributes to the occlusal and skeletal changes. Previous studies claim that the amount of MPDguided protrusion is an essential contributor to adverse events.27 Doff et al28 found an association between a decrease in overbite and the degree of mandibular advancement attributed to an MPD. The mean mandibular advancement with the MPD at the 10-year followup in our study was 6.5 mm, which was identical to the baseline advancement for the entire group29, even though all patients were offered to change their MPDs if needed during the 10 years. These data suggest that the degree of protrusion with an MPD over time can be affected by the mesial drift and would probably be more significant after 10 years. A shortcoming of our study was the use of analog cephalograms at the baseline and a digitalized technique at the 10-year follow-up. Although we corrected for the difference in the magnification factor between the 2 techniques, a systematic error may have been introduced. The test-retest reliability was excellent and the angle measures appeared to be more robust than the measures of distance; consequently, the values for the length of the mandible and hyoid position must be interpreted cautiously. From the long-term perspective, 80%-90% of MPD users exhibit occlusal changes, half of them with favorable changes. Class II Division 1 gets less horizontal overjet and vertical overbite. The other half develop unfavorable changes, Class I involving a frontal edge-toedge situation and Class III involving an even further advanced mandible.14,15 The anterior shift of the mandible may be associated with a posterior open bite; whereas, other shifts retain posterior contacts but are associated with an altered occlusion.14 Bondemark et al13 published a pilot study that reported an increased mandibular length (Cd-Pg) after 2 years of using an MPD. We did not confirm this finding in our 2-year follow-up.8 However, at the 10-year
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follow-up, the mandibular length and the hyoid position to the mandibular line increased significantly, regardless of the use of an MPD. This phenomenon may reflect a physiological change, or it might have been a technical misinterpretation of the digitalization of the baseline analog cephalograms. From a statistical perspective the sample is limited, and the SD at many measures is large, and consequently the P values should be interpreted cautiously. CONCLUSIONS
Long-term nocturnal use of an MPD caused retroclination of the maxillary incisors and proclination of the mandibular incisors with consequent decreased overjet and overbite. Both MPD users and MPD-stopped users obtained increased mandibular length and lower position of the hyoid bone which can be a normal physiological change with age. ACKNOWLEDGMENTS
The authors thank the Department of Oral Radiology, € € Public Dental Service, Region Orebro County, Orebro, Sweden for the radiological support.
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20. George PT. A new instrument for functional appliance bite registration. J Clin Orthod 1992;26:721-3. 21. Araie T, Okuno K, Ono Minagi H, Sakai T. Dental and skeletal changes associated with long-term oral appliance use for obstructive sleep apnea: A systematic review and meta-analysis. Sleep Med Rev 2018;41:161-72. 22. Doff MH, Finnema KJ, Hoekema A, Wijkstra PJ, de Bont LG, Stegenga B. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on dental side effects. Clin Oral Investig 2013;17:475-82. 23. Fransson AMC, Kowalczyk A, Isacsson G. A prospective 10-year follow-up dental cast study of patients with obstructive sleep apnoea/snoring who use a mandibular protruding device. Eur J Orthod 2017;39:502-8. 24. Alessandri-Bonetti G, D’Anto V, Stipa C, Rongo R, IncertiParenti S, Michelotti A. Dentoskeletal effects of oral appliance wear in obstructive sleep apnoea and snoring patients. Eur J Orthod 2017;39:482-8. 25. Pliska BT, Nam H, Chen H, Lowe AA, Almeida FR. Obstructive sleep apnea and mandibular advancement splints: occlusal effects and progression of changes associated with a decade of treatment. J Clin Sleep Med 2014;10:1285-91. 26. Pancherz H, Bjerklin K, Hashemi K. Late adult skeletofacial growth after adolescent Herbst therapy: a 32-year longitudinal follow-up study. Am J Orthod Dentofacial Orthop 2015;147: 19-28. 27. Marklund M, Franklin KA, Persson M. Orthodontic side-effects of mandibular advancement devices during treatment of snoring and sleep apnoea. Eur J Orthod 2001;23:135-44. 28. Doff MH, Veldhuis SK, Hoekema A, Slater JJ, Wijkstra PJ, de Bont LG, et al. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on temporomandibular side effects. Clin Oral Investig 2012;16:689-97. 29. Fransson AM, Tegelberg A, Svenson BA, Wenneberg B, Isacsson G. Validation of measurements of mandibular protrusion in the treatment of obstructive sleep apnoea and snoring with a mandibular protruding device. Eur J Orthod 2003;25:377-83.
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