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EVALUATING STABILITY CHANGES OF MINISCREW IMPLANTS USING RESONANCE FREQUENCY ANALYSIS IN BEAGLE DOGS Derid S. Ure, B.S., D.D.S. An Abstract Presented to the Faculty of the Graduate School of Saint Louis University in Partial Fulfillment of the Requirements for the Degree of Masters of Science in Dentistry 2010 Abstract Purpose: This study evaluated changes in miniscrew implant (MSI) stability over eight weeks using resonance frequency analysis. The study was designed to evaluate the impact of pilot holes and placement sites on changes in stability. Method: Implant Stability Quotient (ISQ) values were measured using the Osstell® Mentor device for 22 MSIs, 1.6 mm in diameter and 9 mm in length, placed in the maxilla of adult beagle dogs (20 months old). Measurements were taken weekly, starting at the time of placement and ending at eight weeks. Using a split mouth design, 1.1 mm wide pilot holes were randomly selected and drilled to a depth of 3 mm for half of the MSIs prior to placement. MSI placement was also divided between keratinized and non-keratinized tissue. Results: Nine of the 22 MSIs failed; all of the failures were related to having been placed in nonkeratinized tissue. MSIs that failed showed significantly (p<0.05) higher decreases in stability during the first three weeks than the MSIs that remained stable. MSIs that remained stable throughout the study also showed decreases in stability during the first three weeks and increases in stability between the third and fifth week (p<0.05). Pilot holes had little or no effect (p>0.05) on MSI stability. 1 Conclusion: Stability of MSIs decreases from week one to week three and increases from week three to week five. Pilot holes do not affect the stability of MSIs. Placement of MSIs into non-keratinized tissue negatively impacts their stability and increases the likelihood of failures. 2 EVALUATING STABILITY CHANGES OF MINISCREW IMPLANTS USING RESONANCE FREQUENCY ANALYSIS IN BEAGLE DOGS Derid S. Ure, B.S., D.D.S. A Thesis Presented to the Faculty of the Graduate School of Saint Louis University in Partial Fulfillment of the Requirements for the Degree of Masters of Science in Dentistry 2010 COMMITTEE IN CHARGE OF CANDIDACY: Adjunct Professor Peter H. Buschang, Chairperson and Advisor Assistant Professor Ki Beom Kim Associate Clinical Professor Donald R. Oliver i DEDICATION This thesis is dedicated to four groups of people: First, to all my teachers when I was younger, for their unselfish dedication to my growth and success. Second, to all my professors at C.A.D.E., for showing me that there is so much more to the profession then just a good career. Third, to my parents, who have provided my personal foundation by their example of consistent, quiet effort, always expecting me to do my best. Fourth, to my wife Rachel and our little family, for their sacrifice, allowing me to pursue my goals and giving me joy along the way. ii ACKNOWLEDGEMENT I would like to acknowledge the following individuals and groups for their help and support of this thesis: Dr. Peter H. Buschang, for chairing my thesis committee. Thank you for all the guidance helping me understand my project more clearly. Dr. Ki Beom Kim, for serving on my committee. Thank you for your support and availability giving me someone that I could always approach with my questions and concerns. Dr. Donald Oliver, for serving on my committee. Thank you for your attention to detail that allowed me to focus not only on the big picture but also the finishing touches. Dr. John Long and the staff at SLU Comparative Medicine, for making every Monday for nine weeks so much fun. Neodent, for providing all the customized miniscrews used during this project. The Saint Louis University Orthodontic Education and Research Foundation, for financial support. iii TABLE OF CONTENTS List of Tables ............................................ v List of Figures .......................................... vi CHAPTER 1: INTRODUCTION ................................... 1 CHAPTER 2: LITERATURE REVIEW History of Skeletal Anchorage Devices in Orthodontics... 5 Understanding Miniscrew Implant Stability.............. 10 Primary Stability ................................... 11 Secondary Stability ................................. 23 Healing Curves: Primary vs. Secondary Stability ..... 32 Measures of Stability.................................. 39 Invasive Methods .................................... 40 Non-Invasive Methods ................................ 45 Summary................................................ 61 References............................................. 62 CHAPTER 3: JOURNAL ARTICLE Abstract............................................... 81 Introduction........................................... 82 Materials and Methods.................................. 86 Animals ............................................. 86 MSI Placement ....................................... 87 Miniscrew Implants .................................. 90 Resonance Frequency Measurements .................... 90 Statistical Analysis ................................ 92 Results................................................ 93 Failures ............................................ 93 Comparison of ISQ Changes of all MSI Over the First Three Weeks of the Study ............................ 95 Longitudinal Changes in ISQ of MSIs Maintained Throughout the Study ............................... 100 Discussion............................................ 101 Conclusions........................................... 110 References............................................ 111 Vita Auctoris ........................................... 116 iv LIST OF TABLES Table 3.1: Weekly ISQ values from placement to eight weeks....................................................94 Table 3.2: Descriptive statistics and statistical comparisons (Wilcoxon signed-rank test) of ISQ values between MSIs that Failed vs. Survived, MSIs that received a Pilot hole vs. no Pilot hole and MSIs placed in Keratinized vs. non-Keratinized tissue from surgery to three weeks....................................................95 Table 3.3: Descriptive statistics and statistical comparisons (Wilcoxon signed-rank test) of changes in ISQ from surgery to three weeks..............................97 Table 3.4: Longitudinal statistical comparisons of ISQs for MSIs that survived the entire study.................100 v LIST OF FIGURES Figure 2.1: Primary and secondary stability curves.......34 Figure 2.2: Implant modes of vibration...................51 Figure 2.3: Minimizing implant modes of vibration........52 Figure 2.4: Orientation of Osstell Mentor transducer during measurements......................................58 Figure 3.1: Primary, secondary and total stability curves over eight weeks..................................83 Figure 3.2: The effect on total stability of a shift in secondary stability......................................84 Figure 3.3: MSIs in Dog A and Dog B by location with pilot hole information...................................88 Figure 3.4: Brassler handpiece...........................89 Figure 3.5: Pilot hole drill.............................89 Figure 3.6: MSI side and top view........................90 Figure 3.7: Smartpeg.....................................90 Figure 3.8: MSI and Smartpeg connected...................90 Figure 3.9: Orientation of Osstell® transducer in relation to the occlusal plane...........................91 Figure 3.10: Orientation of Osstell® transducer in relation to the Smartpeg and MSI.........................91 Figure 3.11: Timing of MSI failures by dog, anterior/ posterior location, tissue type and pilot hole presence..94 Figure 3.12: ISQ over the first three weeks of failed and survived MSIs........................................96 Figure 3.13: ISQ over the first three weeks for pilot vs. no pilot hole MSIs...................................96 vi Figure 3.14: ISQ over the first three weeks for keratinized vs. non-keratinized placement of MSIs........97 Figure 3.15: Change in ISQ over time for MSIs that failed and survived over the first three weeks...........98 Figure 3.16: Change in ISQ over time for MSIs with pilot hole vs. no pilot hole over the first three weeks..99 Figure 3.17: Change in ISQ over time for MSIs placed in keratinized vs. non-keratinized tissue over the first three weeks........................................99 Figure 3.18: Mean ISQ values of MSIs that survived the entire study from placement through week eight..........101 Figure 3.19: Stability of dental implants from placement through week eight......................................105 Figure 3.20: Mean ISQ values of MSIs that survived the entire study from placement through week eight divided by predominant stability type...........................105 vii CHAPTER 1: INTRODUCTION One of the challenges facing orthodontics is the control of unwanted tooth movement. The ability to limit un- wanted tooth movement can often lead to the successful treatment of complex malocclusions that otherwise would be nearly impossible to treat. Anchorage, defined as minimiz- ing unwanted tooth movement, has long been an important consideration for practitioners since the beginning of the specialty. Recently, skeletal anchorage in the form of miniscrew implants (MSIs) has grown in popularity in orthodontics as a means to selectively control tooth movement. The use of skeletal anchorage has allowed the improved treatment of some of the most difficult malocclusions. The explosion of the use of MSIs has revealed that one of the problems with this type of treatment is the rate at which MSIs fail. The success rates reported in the literature range from less than 50% to over 95%.1-4 The unpredictability of MSIs lim- its their usefulness as a treatment modality. Research suggests that there are a number of factors that affect MSI failures including, mobility, excessive heating of the bone during placement, placement in keratinized vs. non-keratinized soft tissue, host factors such as 1 uncontrolled diabetes, excessive loading and poor oral hygiene. While all of these factors have been associated with failure, the actual cause of all MSI failure is the loss of bone-to-implant contact and consequently, stability. Stability can be divided into two types, primary sta- bility, a mechanical interlocking between the implant and surrounding bone directly after placement, and secondary stability, a biological phenomenon that begins soon after placement where bone surrounding the implant is remodeled and new bone is added. Secondary stability develops as a result of the healing process of bone. The overall stabil- ity experienced by a MSI is a combination of primary and secondary stability. Understanding changes in MSI stabil- ity over time could lead to the development of clinical management techniques that could enhance stability and consequently, improve the predictability of the success of MSIs, enhancing their usefulness to the profession. Various techniques have been suggested as a way to study stability of MSIs. Some examples of measures of sta- bility include, insertion torque, removal torque, histomorphometric studies and pullout. The problem with these measures of stability is that they require the destruction of the bone-to-implant contact, rendering them not useful for clinical use. Other less invasive methods have also 2 been proposed. The most promising of these methods, reso- nance frequency, has been used to successfully study the stability of dental implants over time in clinical situations. There is a need to better understand the changes in stability experienced by miniscrew implants in order to develop methods to improve the predictability of implant success. It is the purpose of this study to determine if resonance frequency can be used to study changes in miniscrew implant stability in dogs over an eight-week period. This study will also evaluate the effect of using a pilot hole and tissue type on the early stability of MSIs. In order to better understand the relationship between miniscrew implants, their success and primary and secondary stability, the subsequent review of the literature will be divided into the following sections: 1. The history of skeletal anchorage will be explored. This will provide un- derstanding of how the concept of using bone as a source of biological anchorage developed. 2. The concepts surround- ing stability will be explored. First, the idea of primary stability will be defined and factors that help determine this stability will be evaluated with special emphasis on the effect of pilot holes and tissue type. Second, the concept of secondary stability will be reviewed. Factors 3 that help determine this stability will be presented and examined in detail. 3. A look at the biological process of healing and how it relates to primary and secondary stability will be considered. 4. Methods to evaluate the stabil- ity of MSIs will be investigated with particular emphasis on resonance frequency as a means to evaluate changes in stability over time. 4 CHAPTER 2: LITERATURE REVIEW History of Skeletal Anchorage Devices in Orthodontics The need to enhance anchorage in orthodontics has led to the development of many methods to control unwanted tooth movement. These methods include the use of Tweed,5 segmented,6 bi-dimensional,7 bioprogressive8,9 and other types of mechanics. In the bioprogressive technique, Rick- etts advocated the use of the cortical plate of the alveolar process as a source of anchorage; by placing tooth roots in close approximation to the cortical bone, it was thought that their movements could be slowed down compared to the other teeth in the arch.8,9 The use of devices that utilize the bone as a direct source of anchorage was envisioned even before Ricketts introduced his concept of cortical anchorage. Using the bone surrounding the teeth as a source of anchorage during treatment has long been a goal of orthodontists. As early as 1945, Gainsforth and Higley used a vitallium screw placed in the ramus of dogs that was then connected to the canine tooth in an effort to enhance anchorage. Unfortunately, when orthodontic forces were placed on the screws they failed. Interest in the use of bone for skeletal anchorage began to move forward following the 5 landmark studies by Brånemark in the late 1950s and early 1960s when he noticed that titanium optical chambers placed in rabbits could not be removed from the bone. Further in- vestigation led him to observe the ingrowth of bone around the titanium devices resulting in what he termed “osseointegration.”10,11 To Brånemark, osseointegration was the lit- eral fusion of bone and titanium. For the purpose of this study osseointegration will be defined as, direct structural contact between living bone and the surface of an artificial implant at the light microscopic level, commonly known as bone-to-implant contact. Soon dentistry came to understand the principles of osseointegration and new restorative procedures were developed that utilized dental implants to replace missing teeth. As dental implants be- came more predictable and used on a wider scale, orthodontists began to realize their potential for supplementing orthodontic anchorage. To retract teeth, Linkow utilized a blade style dental implant with rubber bands attached.12 The problem with us- ing this type of anchorage is the dental implant must be placed before orthodontics commences and given time to osseointegrate. As teeth move relative to the dental implant during orthodontic treatment, the location of the implant may not end up in the ideal position for restorative pur6 poses. To overcome this limitation, Kokich13 and Smalley and Blanco14 developed protocols to determine proper placement so that dental implants used for orthodontic tooth movement were in the proper location for restorative treatment. These approaches to skeletal anchorage all required dental restorations in order to justify the placement of the implants. In addition to restorative need, they also required space for placement. This limited the usefulness of these types of skeletal anchorage devices to a small percentage of patients. In response to growing interest in skeletal anchorage and to overcome the limited usefulness of dental implants as a source of orthodontic anchorage, new types of skeletal anchorage systems developed. These new anchorage systems are placed specifically for anchorage purposes and removed after being utilized for orthodontic purposes. Roberts et al. introduced the first of these orthodontic specific systems.15,16 It consisted of a miniature ver- sion of the dental endosseous implant that was placed in the retromolar area of the mandible and was removed after having been used for orthodontic anchorage. This system however, was only useful for anchorage purposes in the man- 7 dible and was often difficult to remove due to osseointegration that occurred during treatment. Wehrbein et al. used small endosseous implants placed in the palate for orthodontic purposes.17 This system of orthodontic anchorage was also limited in its usefulness since removal required the elimination of bone circumferentially around the implant in a process called trephination. To overcome this limitation a palatal onplant was developed.18 Instead of placing the implant within the bone, this system was placed under the periostial membrane in direct contact with the cortical portion of the bone. It required that the bone grow into the base of the onplant to ensure its success as a source of anchorage. The placement and removal surgeries, time required for osseointegration, and difficulty of removal, also made this anchorage system less than ideal for orthodontic purposes. The use of titanium plates for rigid fixation of orthognathic surgery patients led to the development of yet another type of anchorage system. Bone plates, developed by Sugawara and Nishimura, were modified titanium rigid fixation plates that were fixed to the bone and then passed through the oral mucosa into the oral cavity and used as a source of anchorage.19 The benefit of this type of system was that it could be placed in both the maxilla and mandi8 ble. However, it still required two surgical procedures, one for placement and one for removal, which limited its usefulness and acceptance by the profession. In an attempt to increase the acceptance of skeletal anchorage by patients and the profession, Creekmore and Eklund introduced the use of surgical screws to intrude maxillary anterior teeth in 1983.20 However, the screw they used was rather large and the surgical procedure was unspecified. In 1997, a formalized insertion protocol for using surgical screws as anchorage was developed by Kanomi.21 The screws he advocated were much smaller that those used by Creekmore and Eklund, with a diameter of 1.2 mm and length of 6 mm. These small surgical screws were the forerunners of the modern miniscrew implants (MSIs). However, it would not be until Costa et al. simplified the placement procedure in 1998, that MSIs started gaining widespread attention in the profession.22 Since 1998 numer- ous MSI systems for orthodontic anchorage have been developed and popularity of MSIs has grown at an ever-increasing rate since they were first introduced. They are now an in- tegral part of many orthodontists’ treatment procedures. In order to maximize efficiency and the success of MSIs, the biological principles surrounding the stability of MSIs must be explored and appreciated. 9 Ultimately, stability of a MSI is a function of the biological changes that occur in the bone surrounding the implant. The source of this sta- bility and how it changes over time will now be considered. Understanding Miniscrew Implant Stability In order for MSIs to be useful to orthodontics as a source of anchorage, it is necessary that they be able to withstand orthodontic forces placed on them and remain in a stable position in the bone until their use is no longer required. Orthodontic forces used for tooth movement usu- ally fall in the range of 1-3 N (roughly 3.5-11 oz or 100300 gm).23 For the purpose of this research, stability of an implant will be defined as the implant’s ability to withstand loading with orthodontic forces. Stability can be divided into two types that are vital to the overall success of the MSI, primary stability, a mechanical phenomenon due to initial contact between the implant and bone, and secondary stability, associated with the remodeling and deposition of new bone around the implant over time.24 Understanding how these types of stabil- ity relate to each other and to overall MSI stability is necessary in order to increase the success rates of MSIs. The concept of primary stability and the factors that af- 10 fect it will now be considered. Then secondary stability will be examined. Primary Stability According to Wilmes et al., primary stability, a mechanical phenomenon derived from the contact of the implant with the surrounding bone, occurs immediately after placement of the MSI.25 For MSIs, the cortical bone surrounding the implant is the major determinant of primary stability.23 Depending on the length of the MSI placed, location and surgical procedure (depth of placement), primary stability can be derived from either mono or bi-cortical placement.26 Primary stability is important for two reasons. First, primary stability is critical from an orthodontic standpoint because it allows for the MSI to be loaded by the orthodontist immediately after placement, which increases efficiency.22,27,28 Second, primary stability is critical for the development of secondary stability.29 The relationship of adequate primary stability and secondary stability can best be understood by considering the stresses surrounding MSIs during placement. Placement of an MSI into bone causes compression of bone and generates stresses in the bone surrounding the im- 11 plant. The nature and severity of these stresses are par- tially determined by the cortical bone thickness.30,31 The thicker the cortical bone, the more the stresses produced by compression of bone concentrate within the cortical plate. These stresses play an important role in the move- ment of the MSI in relation to the surrounding bone. If these stresses are adequate, the MSI is held in a rigid position, ensuring an adequate environment in which to remodel the bone surrounding the implant and enhance secondary stability. If the stresses are not sufficient then movement of the MSI relative to the surrounding bone can lead to failure. This lack of adequate stability has been identified as a risk factor for early implant loss due to failure of osseointegration.29,32 Implant movement may lead to mi- crofracture, necrosis, bone resorption and eventual formation of a fibrous capsule. As movement occurs, additional trauma to the bone in the form of microfractures in bone surrounding the implant can occur. When the body removes the damaged bone during the healing process, the MSI becomes even less stable and movements may become even larger. These movements can lead to the formation of fi- brous tissue instead of bone, as demonstrated with blade implants.33,34 Small implant movements lead to the recruit12 ment of pluripotent bone cells to the area needing repair. These cells can differentiate into bone, cartilage and fibrous tissue.35 Similar to fracture healing, if movement in the repair area is present, then these cells differentiate into fibrous tissue, which cannot be converted into bone. Once fibrous tissue forms between the implant and bone, failure of the MSI can be expected.36 Without adequate pri- mary stability and bone support, secondary stability could be limited due to the formation of a fibrous capsule and the miniscrew could eventually loosen. If the stresses during the insertion of the MSI are excessive then failure of the implant to attain secondary stability can also be anticipated. The compression of bone during insertion generates circumferential hoop stresses.37 Hoop stress is defined as a mechanical stress produced by rotationally-symmetric objects that results from forces acting circumferentially (perpendicular both to the axis and to the radius of the object).38 While hoop stresses that press the bone against the MSI provide primary stability, excessive stresses can be detrimental to the long-term stability of the implant. Excessive hoop stresses can pro- duce local ischemia which leads to bone necrosis and consequently micromotion of the implant.37 As previously de- scribed, this micromotion may often lead to the formation 13 of a fibrous capsule surrounding the implant and to eventual failure. However, hoop stresses are not the only stresses encountered during placement of a MSI. As a miniscrew is inserted, the threads of the screw are positioned so that they draw the screw into the bone. This creates a vertical stress on the bone immediately surrounding the implant known as a shear stress. As more bone is contacted during placement these shear stresses increase.39 If these stresses become excessive, the bony ma- terial surrounding the threads becomes stripped and the screw spins freely.40,41 This leads to a compromise in the stability of the screw.42 While the importance of understanding the nature of primary stability cannot be over stated, factors that contribute to this stability are also important to comprehend. Determinants of Primary Stability There are three general factors that determine the extent of the primary stability, including bone attributes, implant design and insertion technique.25 14 Bone Attributes Bone attributes play an important role in the primary stability of MSIs. One characteristic of bone, cortical thickness, can have a large impact on the stability of miniscrews. It has been reported that thicker cortical bone is considered better for MSI placement.28,43 If primary stability is derived from bone-to-implant contact, and most of that contact is found in the cortex, then a thicker cortex will yield a higher primary stability, other factors being equal. One measure of primary stability, insertion torque, has been shown to have a direct relationship with cortical thickness.1,25,44-46 The thicker the given cortex, the higher the accompanying insertion torque. Another measure used to evaluate primary stability, pullout strength, also shows a positive relationship with cortical thickness.42,44,47,48 The thicker the cortex the higher the force required to pull the MSI out of the bone. Bone density also plays a key role in primary stability. Studies evaluating bone density have demonstrated positive correlations with insertion torque and pullout strength.25,42,47 It makes intuitive sense that the higher the density of bone, the greater the primary stability. This could easily be explained by higher initial bone-toimplant contact. Recently, Hung, using synthetic bone, 15 demonstrated the relationship of bone density and stability for MSIs.49 In dental implant literature, this relationship has been shown to be so strong that rating systems of bone density have been developed.50,51 Ryken et al. developed a mathematical model based on bone density and insertion torque to predict the stability of screws used in spinal surgery.52 Studies using endosseous implants have shown that the quality of the bone surrounding the dental implant can have a significant effect on the stability.39,48,53 Having adequate bone density to provide primary stability is considered so important for dental implants that a novel insertion method was introduced by Büchter and others. This technique attempts to increase the density of the bone by compacting the bone surrounding the implant during placement; accomplished by inserting successively larger compressive osteotomes into a smaller than normal pilot hole.54 Implant design The design of the MSI can affect primary stability. Multiple studies have evaluated the effect of implant design on primary stability. Length, diameter, shape, and thread design have all been examined and have been found to 16 be significant factors when evaluating insertion torque and pullout strength to measure primary stability.55,56 Wilmes et al. evaluated miniscrew diameter and shape and related it to insertion torque.57 They found that larger diameter MSIs exhibited higher insertion torque. They also showed that conical shaped miniscrews had higher insertion torque values. Lim and others evaluated the effects of length, diameter and shape and their relation to insertion torque.45 They concluded that all these implant design factors play a role in determining insertion torque. Longer miniscrews and larger diameter miniscrews had higher insertion torque values. They also determined that tapered or conical shaped implants had higher insertion torque values, suggesting higher primary stability. Brinley et al. evaluated several miniscrew designs in synthetic and cadaver bone to determine the effect of thread design on insertion torque and pullout strength.58 They concluded that decreased thread pitch, the distance between adjacent threads of a miniscrew, led to an increase in pullout strength. The study also evaluated the effect of fluting on insertion torque and found that it would significantly increase primary stability. 17 Surgical Procedure Another factor that can affect the primary stability of miniscrews is the method of placement. During placement of a MSI the general goal is to perform the placement with as little trauma as possible. A minimally traumatic inser- tion theoretically gives the miniscrew the best chance to go through its healing phase quickly and uneventfully. Trauma necessitates bone remodeling, healing and formation of woven bone. Due to its poor organization and structure, woven bone may provide limited support to withstand orthodontic loading forces. In order to minimize trauma several surgical techniques have been developed. The major tech- nique advocated to minimize the trauma associated with MSI placement includes the preparation of the implant site by drilling a pilot hole. The rational behind the use of a pilot hole is to minimize the stresses of the bone by removing a portion of the bone prior to screw placement. Excessive stresses can lead to microfracture of the bone or ischemic necrosis and eventual failure of the screw.37 Pilot holes were originally used by surgeons to allow placement of screws into bone. In 1959, Boucher was one of the first to use pilot holes when placing large pedicle screws during spinal fusion surgery.59 18 He advocated the use of pilot hole placement to help prevent premature screw failure, which was common at the time. His goal was to create a more stable fixation resulting in higher surgical success rates. The use of pilot holes became commonplace in spinal surgery by the 1980s.60 In order to understand how a pilot hole affects the holding power of a screw in bone, Daftari et al. evaluated correlations between insertion torque, pullout strength and pilot hole.61 Pilot holes for spinal surgery were necessary due to the size of the screws being placed.60 The success of this method in spinal fusion surgery led to the adoption of pilot holes by other surgical specialties. Craniofacial surgeons utilized pilot holes as part of their surgical protocol, even though they used much smaller screws, comparable to the size of MSIs.62 Because placement of screws in the medical literature advocated the use of pilot holes, they were thought to be a good idea during MSI placement as well.21 However, to sim- plify placement and to overcome some of the risks of placing a pilot hole, such as, nerve damage, tooth damage and bone necrosis, some began to advocate the placement of screws without a pilot hole.63 Screws were designed to be self-drilling and claimed easier placement due to the simplified procedure. Following the use of the non-drill in- sertion procedure, reports of screw breakage during place19 ment began to surface.64-66 High insertion torque values and screw diameter were given as a reason for screw fracture.65 So limiting insertion torque became a valid reason to place MSIs with a pilot hole. Chen et al. showed that MSIs placed without pilot holes had higher insertion torque values than those that had pilot holes drilled.64 This was similar to work performed by Oktenoglu and colleges.67 Another factor that can lead to increased insertion torque is the density of the bone in the area of placement. The denser the bone the higher the insertion torque.64,68 Ex- cessive insertion torque not only increases the risk of fracture of the screw, but also may lead to failure at a later time.1 It has become generally well accepted that in areas of the mouth where there is bone with a higher density, i.e. the posterior mandible, the use of a pilot hole may be the prudent method of placement.1 It is important to consider the size of the pilot hole. Hung, concluded that increasing the pilot hole di- ameter lowers the insertion torque and pullout strength of miniscrews in synthetic bone.49 She also showed that the density of the bone surrounding the implant affected these measures. Heidemann and coworkers, who studied the rela- tionship of pilot hole size and stability, found that a pilot hole up to 85% of the external diameter of the screw 20 could be used without any loss in pullout strength.69 This was confirmed in work by Gantous and Phillips when they showed that a pilot hole 85% of the external diameter of the screw allowed for adequate stability.62 However, if the bone is of lower quality or density, a smaller diameter pilot hole should be used.70 It is clear that the use of a pilot hole decreases primary stability, as measured by insertion torque, but what effect does it have on the secondary, long term, stability? In their work involving the impact of pilot holes, Präger et al. showed no difference in bone-to-implant contact after 12 weeks of healing between groups of implants placed with and without pilot holes, indicating that the use of pilot holes has no impact on secondary stability.71 In contrast, Heidemann et al. found a very slight decrease in bone-to-implant contact in the pilot hole group.72 While advocates of pilot holes suggest that their use minimizes trauma during placement, others contend that their use can actually cause excessive trauma. Heidemann et al. indicated that the use of pilot holes carries its own set of risks, including damage to the teeth and surrounding structures, as well as drill breakage and thermal insult to the bone.63 As a living biological system, bone is sensitive to adverse thermal episodes. 21 It has been shown that an increase above 47° Celsius can cause necrosis of the bone.73,74 As previously explained, necrosis may eventually lead to MSI failure. Thermal insult can be pre- cipitated by excessive pressure on the drill during placement,75 a worn out drill,75 lack of irrigation76 and excessive speed of the drill.76 To overcome these negative side effects of using a pilot hole, many practitioners prefer a drill-free placement protocol. This type of placement is suggested because it is quicker, may be less destructive if the root is contacted and generates less heat. However, placement of an MSI without a pilot hole may still generate excessive heat.77 This is due to the friction between the implant and bone which can be measured by insertion torque. The higher the insertion torque the higher the friction between the bone and screw, producing greater heat upon insertion.66 This may be especially relevant in dense bone that has a higher insertion torque. For the placement of an MSI, one factor that determines the amount of friction is the thickness of the cortical plate. So anatomical areas, such as the posterior mandible, that have thicker cortical plate, may benefit from the surgical protocol of properly placing a small pilot hole.66 22 The use of pilot holes and other modifications of the surgical procedure for MSI placement are important because they ultimately have an effect on the long-term secondary stability of the screw. It is secondary stability which provides the benefit of MSIs to orthodontics by allowing loading and resistance to movement over a clinically useful time period. Consequently, an understanding of secondary stability is imperative. Secondary Stability Secondary stability is produced by biological processes that include the deposition of new bone and the remodeling of immature bone around an implant.23,78 stability is dependent on primary stability. Secondary With adequate primary stability (lack of implant mobility), bone can form and remodel around the implant. This process leads to an increase in secondary stability of the implant.23 It has been shown in dental implant literature that this increase in stability takes place approximately 4 weeks after placement of the implant.24,79 While primary stability provides the miniscrew with sufficient stability to withstand 1-3 Newtons orthodontic forces initially, secondary stability is needed to allow 23 the implant to resist the orthodontic forces used throughout the duration of treatment.23 This longer-term stability is provided by the osseointegration of the MSI with the newly formed bone being laid down. It is thought that the deposition of new bone and the remodeling of previously deposited bone occur as a response to stresses experienced by the bone in the area immediately surrounding the implant. Bone and implants have a different elastic moduli (a measure of stiffness). This difference in moduli creates stresses within the bone when the bone is bent.80,81 During function, force is applied to the bone, causing the bone to bend. Because bone has a lower modulus of elasticity (17.9 GPa)82 than titanium alloy (116 GPa),83 it bends more than an implant. This differential bending generates stresses in the bone surrounding the implant. These stresses are thought to promote remodeling and healing of the bone.78 It is thought that the generation of stresses during mastication accounts for the abnormally high levels of cortical bone remodeling (100-200%) that occur during the first year after dental implant placement.23 The normal rate of remod- eling in the cortex is 2-10% per year.23 Understanding what secondary stability is and the process of osseointegration provides the opportunity to review what factors can affect this stability. 24 Determinants of Secondary Stability Insufficient primary stability (i.e. mobility) facilitates the formation of fibrous tissue instead of bone at the implant surface.29,33 This may lead to excessive mobil- ity and eventual implant failure. The following discussion of determinants of secondary stability presupposes that adequate primary stability existed. Host factors Host factors play an important role in determining secondary stability. The body’s ability to heal itself is paramount to the development of long-term implant stability because the healing process is essentially what occurs around an implant after placement. In examining dental im- plants, Ashley et al. determined that osteoporosis, uncontrolled diabetes, smoking and parafunctional habits, interfered with the healing process and were risk factors for implant failure.84 Poor bone density has also been identified as a risk factor for implant failure.85 It appears that bone must be of adequate quality to help maintain a certain level of stability in order to prevent the loosening and failure of 25 implants over time. This concept is supported by studies that show different success rates for implants placed in anatomical areas with differing quality of bone.46,2,86 Simi- larly, the density of bone has also been sited as a risk factor for premature failure of miniscrews.1 Along with physiology and anatomy, host behavior has been shown to have an effect on secondary stability of MSIs. The ultimate cause of implant failure is loss of bone-to-implant contact. Inflammation around the implant, leading to mobility and inhibition of osseointegration has been identified as a risk factor for MSI failure. Oral hy- giene has been shown to play an important role in minimizing inflammation around implants.2,3,87 Poor oral hygiene has been suggested as an important factor relating to MSI success.2 It appears from work by Park et al. that care around the implant is the most important aspect of oral hygiene.2 Without the foundation of a biologically sound host and proper oral hygiene, the development of secondary stability is not predictable. Implant Design Similar to primary stability, implant design can play an important role in the development of secondary stabil- 26 ity. MSIs that have a good design for primary stability are likely to have a good chance for secondary stability. Designs that produce adequate bone-implant contact minimize the micromotion of the screw and allow for the development of additional bone-implant contact. Recent advances in dental implants have shown that treating the surface of the implant where it contacts bone can enhance the deposition of secondary bone and, consequently, stability.88,89 Traditionally, MSIs have been pro- duced with a machined smooth surface. This surface can be treated in a number of ways in order to enhance bone-toimplant contact. In a process termed plasma spraying, im- plants can be coated with bioactive materials such as hydroxyapetite.90,91 Bioactive proteins, such as melanin, can also be wiped on the surface of the implant prior to placement.92 The most common treatment is to roughen the surface of the implant via sand blasting or acid etching, or a combination of both, to create more surface area microscopically for bone to contact. This process, called SLA (sand blasted, large grit and acid etched) treatment, has been used on MSIs in an attempt to increase secondary stability. Work by Ikeda showed significantly more bone-to-implant contact for SLA treated MSIs than conventional smooth surfaced ones.93 It may be possible to enhance secondary sta27 bility of MSIs via surface treatment. The concern with this approach is the fear of breakage upon removal due to excessive osseointegration.94 Kim et al. reported higher total energy required for removal of SLA treated implants, but showed no difference in maximum removal torque between SLA treated and conventional MSIs.95 Surface treatment of MSIs may be a future method to enhance secondary stability. Surgical Procedure Another factor that can impact secondary stability is the procedure used during insertion. During surgical placement the goal is to perform the procedure so that there is an optimal environment for healing to occur. Therefore, all of the issues discussed previously that affect primary stability, would also affect long-term stability. There are, however, additional surgical factors that affect secondary stability. Location of placement has been shown to affect success rates of MSIs. It has been proposed that root proxim- ity is a major factor for screw failure.96 Kang et al. showed a failure rate of 79.2% for screws that invaded the roots vs. 8.3% failure rate for those only in alveolar bone.97 It was suggested that when a miniscrew is in con- 28 tact with the root, micromotion is introduced by the root during mastication, which leads to inflammation and eventual failure of the screws. Avoidance of the roots during placement is important. Insertion torque has also been shown to affect secondary stability. A survey conducted by Buschang et al. showed that practitioners that measure insertion torque have a significantly lower failure rate than those who do not measure this important parameter.4 This is in agreement with work by Motoyoshi et al., who reported a range of insertion torque values that will lead to optimal success rates.1 Insertion torque values that are too high or too low can lead to compromises in implant stability. Loading of MSIs has been a topic of debate for some time, with timing of load having been especially controversial. MSIs.98 Immediate loading may promote the stability of Animal studies have also reported that immediate loading of MSIs can be successful.99,100 Others suggest a healing period of four weeks before loading the implants.101 Motoyoshi et al. found that failure rates for early loaded (average 2.6 weeks after placement) MSIs were significantly higher, especially in areas of less dense bone in adolescents than for MSIs loaded after 12 weeks.102 The general consensus at this time seems to be that immediate loading 29 is considered appropriate. However, most proponents of early loading are also advocates of using light forces initially with MSIs. Magnitude of loading may effect secondary stability. Excessive loading has been shown to be a risk factor in MSI failure.103-105 Büchter et al. showed loosening of implants subjected to forces of 9 N (approximately 900 grams).103 Timing of loading and magnitude of force application may not be the only force related factors that contribute to long-term stability. Costa and co-workers showed that a torsional force directed in the unscrewing direction could cause the implant to fail.106 It appears that loading can play a significant role in the long-term stability of MSIs, but many questions remain unanswered. The soft tissue surrounding the MSI can also affect secondary stability. A relationship between the characteris- tics of the soft tissue and success rates of MSIs has been proposed.2,3,107 There are two types of oral tissue into which implants can be placed, attached gingiva (keratinized) and movable mucosa (non-keratinized). The concept that tissue type can affect the success of an implant originates in the dental implant literature. For success of dental implants it has been recommended that they should only be placed in attached gingiva.108,109 30 This recommenda- tion is based on the prevention of peri-implantitis that forms around dental implants and is ultimately responsible for their failure. Without an adequate amount of attached gingiva, inflammation around the implant can persist, leading to bone loss and eventual failure.108-110 This is thought to be so important, that soft tissue grafting for dental implants is often performed prior to implant placement in order to provide an adequate zone of attached gingiva.111 It is also thought that placement tissue is a factor in MSI success.23 In a comprehensive review of the literature, Reynders and co-workers suggest placement of MSIs in the attached gingiva in order to avoid inflammation around the implant.86 However, this recommendation was based on only three articles, two of which were not actual studies.3,112,113 Antoszewska et al. also reported significantly higher success rates for MSIs in attached gingiva compared to movable mucosa.114 This could be explained in several ways. First, movable mucosa may cause micromotion of the implant if it does not possess adequate primary stability leading to implant failure. this concept. There are, however, no studies to support Second, movable mucosa does not provide an adequate seal around the neck of the implant leading to possible microbial invasion and inflammation, which can lead to implant failure.2,3 Park and coworkers showed that 31 once inflammation was present in areas of non-keratinized soft tissue, it persisted.2 In contrast, Chaddad et al. re- ported no difference in the success rate of MSIs based on soft tissue environment.107 Lim et al. also found that soft tissue was not a factor associated with the success of miniscrews.115 Currently, the relationship that soft tissue type has with secondary stability is unclear. With an understanding of primary and secondary stability established, it is important to explore the changes that occur during each type of stability, giving each its unique attributes and role in determining overall success of MSIs. One way to understand these changes is to examine the healing curves for primary and secondary stability. Healing Curves: Primary vs. Secondary Stability The purpose of stability of MSIs in orthodontics is to obtain adequate rigidity to resist orthodontic forces for the duration of treatment. Consequently, it is important to understand how stability changes after insertion. It is well understood that after insertion of a dental implant there is a primary mechanical stability due to the tight fit of the implant with the bone (bone-to-implant contact).116 Over time however, the bone-to-implant contact 32 changes as the body remodels the bone immediately surrounding the implant. Bone-to-implant contact continues to change as additional bone is laid down around the implant. This new bone increases the stability, of the implant until the stability plateaus and remains relatively constant for the remaining life of the implant.117 The dynamic nature of the bone surrounding the implants infers that bone-toimplant contact is in a state of change as the healing process takes place. Since bone-to-implant contact deter- mines stability, it would be reasonable to expect that the stability of an implant could also fluctuate. It is well understood in the dental implant literature that the stability of implants changes over time.118 This concept was described in a graphical representation during a review of the dental implant literature by Raghavendra et al. (see Figure 2.1).118 33 Figure 2.1: Primary and Secondary Stability Curves. Adapted from Raghavendra et al.118 They suggest stability can be broken down into two types, primary stability and secondary stability. The com- bination of these two sources of stability yields the total stability of the dental implant. It is important to note that in the dental literature we evaluate and study the total stability curve and have limited techniques to separate primary from secondary stability. While the primary and secondary stability curves make intuitive sense they are merely used to describe the shape of the total stability curve. Another challenge associated with evaluating these curves is that we can look at them statically but have limited methods to examine them dynamically. 34 Primary Stability Healing Curve Primary stability can be measured by various means including insertion torque, histology, radiology, cutting torque, pulsed oscillation, impact hammer method, and resonance frequency analysis. All these measures will be exam- ined in more detail in the following section. Much re- search has been performed to evaluate primary stability for dental implants, but there is limited understanding of how primary stability changes over the first weeks after MSI placement. Once insertion takes place, the body begins its healing process to remove damaged bone from around the implant. This early part of the healing process is characterized by has increased osteoclastic activity.118 Consequently, sta- bility begins to decrease as bone is removed from around the implant. The transition from primary to secondary sta- bility during the first weeks of healing may also include the replacement of lamellar bone with softer woven bone, further decreasing the stability of the implant.116 Accord- ing to Cochrane et al., this process may contribute to the loss of primary bone contact and consequently can compromise stability.116 Decreased mechanical stability due to 35 lower bone-to-implant contact explains the shape of the primary stability curve. Primary stability is the highest immediately after insertion and declines thereafter.118 This phenomenon was reported by Luzi and et al. when they noted a decrease in bone-to-implant contact between week one and week four for loaded MSIs in monkeys.119 Others have used resonance frequency to evaluate the change in stability of dental implants over time.120,121 Ersanli et al. took measurements at surgery, three weeks, six weeks and six months.120 They found a significant decrease from sur- gery to three weeks. Balshi et al. Followed the stability of 276 dental implants from placement to ninety days.122 Measurements were taken at surgery, 30 days, 60 days and 90 days. Their results showed a statistically significant de- crease from 0-30days. In another study, Barewal et al. evaluated the changes in stability from zero to ten weeks according to bone type.123 They found a decrease in stabil- ity from placement to week three in bone that was considered type 2,3 or 4 (according to the index proposed by Lekholm and Zarb).50 After initial loss of bone-to-implant contact, if for some reason (i.e. infection, fibrous tissue formation or lack of adequate primary stability) new bone does not form around the implant, secondary stability never develops leading to screw failure. 36 Secondary Stability Healing Curve Secondary stability is a result of the process of bone deposition and remodeling that occurs following implant placement. It pertains to the healing process that re- places damaged bone surrounding the implant and deposits of new bone, leading to an increase of the secondary stability curve.118 This process of osseointegration has been de- scribed in the dental implant literature. Schwartz and Boyan described the histological events of osseointegration.124 Initially, serum proteins attach to the implant surface immediately after placement. Then dur- ing the first three days of healing, mesenchymal cells are attracted, attach and proliferate. produces osteoid. By day six these cells The calcification of this osteoid is complete by the second week and remodeling of this new bony material commences by week three. Berglundh et al. described similar events.125 Within two hours of implant placement, erythrocytes, neutrophils, and macrophages coalesce in a fibrin network. and mesenchymal cells appear by day four. Osteoclasts Woven bone is produced by day seven and newly formed bone connecting the woven to the parent bone can be seen by the second week. There is marked formation of woven and lamellar bone by week four and extensive remodeling occurs from week 8-12. 37 Other studies have also demonstrated the increase in osseointegration related to secondary stability. Melson and Lang showed an increase in bone-to-implant contact and bone density for MSIs over the first six months after placement.126 In agreement with this, Moringa et al. evalu- ated bone formation around titanium coated plastic implants that were similar in size to MSIs.127 The implants used in their study were 1.6 mm in diameter and 7 mm in length. They evaluated the quantity and quality of the bone over time using light microscopy, transmission electron microscopy and micro computed tomography.127 They demonstrated bone formation begins a small distance from the implant and then by 28 days nearly covers the implant. They also con- firmed that, over time, the density of the bone surrounding the implant increases. Using resonance frequency analy- sis, others have also shown an increase in the stiffness in the bone surrounding an implant as a function of time.120,121,128 Boronat López et al. described an increase of stability for implants that began to take place the fourth week following dental implant placement.79 al. Stadlinger et reported an increase in implant stability from one month to two months post placement.129 They noted in their study that implant stability values were lower after two months than at the time of placement. 38 Taking measurements every thirty days, Balshi et al. reported a statistically significant increase in stability from 30 to 60 days but no difference from 60 to 90 days.122 Barewal et al. also re- ported an increase in implant stability from week three to week six but then showed no change in implant stability from week six to week ten.123 It is important to note that while these studies appear to support the idea of the healing curve for secondary stability, they are ultimately evaluating the total stability and indirectly infer the shape and magnitude of the secondary stability curve. With an understanding of the healing process for implants and its relation to stability, it is now important to understand how stability is measured clinically. Measures of Stability The stability of a miniscrew implant is determined by its ability to resist loading and is a function of the implant’s contact with surrounding bone. The osseointegra- tion of the implant changes overtime. Its quantification provides important information about healing around the implant. There are many methods that have been used to evaluate stability.130 These methods can be categorized as 39 invasive and non-invasive based on their interference with the osseointegration process. Invasive Methods Methods to evaluate implant stability are considered invasive if they disrupt the processes of osseointegration. Several methods of measurement can be included in this grouping. Insertion torque is probably the most common measure of an implant’s primary stability. This technique was de- scribed by Hughes and Jordan as a method to estimate initial stability of surgical screws.39 Insertion torque meas- ures the magnitude of rotational force required to insert a screw into bone and is reported in Newton/cm.39,40 As a screw is inserted, the bone compresses around the implant. This compression leads to friction between the implant and bone and is measured as insertion torque. This torsional force is low as the screw is first placed into the cortex. It increases until the entire cortical layer is engaged. The maximum value is attained when the head of the screw makes contact with the cortical plate.39 If the screw is inserted past this point then stripping of the surrounding bone occurs and the holding power of the implant is lim- 40 ited.42 Insertion torque is a measure of the bone/tissue interface and has been shown to correlate with bone density and implant stabiliy.37,131,132 A minimal amount of insertion torque is necessary for primary stabiliy.37,133 Chaddad et al. reported this minimal value to be about 15 N/cm for human subjects.107 This, however, may be due to the gross method of measurement of insertion torque used in the study. In contrast Chen and co-workers reported that MSIs with insertion torques of 3.5 to 5.6 N/cm in the maxilla of dogs and 7.4 to 8.7 N/cm in the mandible experienced high success rates.64 It appears that there is also a maximum insertion torque that corresponds to increased implant failure.1 Motoyoshi et al. recommended a range of insertion torques from 5 to 10 N/cm that correspond with high levels of success for MSIs with a diameter of 1.6 mm.1 Torque lev- els outside of this range may lead to implant failure or breakage. Insertion torque has its limitations as a measure of primary stability. It is only useful for measuring stabil- ity at the time of placement. Longitudinal data cannot be collected and changes in bone surrounding the implant cannot be evaluated with this method. Another invasive method to evaluate primary stability is the use of cutting torque resistance. 41 This technique measures the energy needed to remove bone prior to implant placement.134 Friberg et al. showed a positive correlation between cutting torque resistance and bone density, which is one of the factors that determine stability.131 The is- sue with this method of measurement is that it is only useful to estimate the implant stability prior to placement. Consequently, repeated measures cannot be made. It is also only used for dental implants where the larger size of the implant necessitates the removal of bone prior to placement. Bone removal prior to placement for MSIs is often not needed, due to their small size, and sometimes not even desirable. This limits the usefulness of this measure for MSIs. The gold standard to evaluate secondary implant stability is histomorphometric measurement. This method exam- ines the bone-implant interface at a microscopic level to determine stability. Bone-to-implant contact, usually re- ported as a percentage of the total implant surface area, is the common way that implants are evaluated histologically.125,135,136 An increase in the percentage of bone-to- implant contact indicates a corresponding increase in stability. Melson and Lang showed an increase in bone-to- implant contact six months after placement of miniscrew implants.126 Other studies have also evaluated the dynamics 42 of bone-to-implant contact around orthodontic miniscrews.97,137-139 Another way to evaluate stability histologically is to count the number of osteocytes in the bone surrounding the screw. The problem with using histologic evaluation to assess implant stability is that it cannot be used clinically. Removal of the implant is re- quired along with a section of the surrounding bone. This is not possible on human subjects. Another method used to measure secondary stability is removal torque. Removal torque measures the critical threshold when bone-to-implant contact is broken. indirect method to evaluate secondary stability. It is an Johansson and co-workers reported on this method when they showed that longer healing times could lead to greater bone-toimplant contact and higher removal torque values.134,135 This relationship was also demonstrated by Kim et al. who used surface treated implants to show that the longer the implant remained in place, the higher the removal torque value.140 Using 1.2 mm diameter implants and pilot holes of 1.0 mm and 1.2 mm, Okazaki et al. showed that removal torque was independent of pilot hole size over a 12-week period.141 There are also limitations to this method of measurement. It is destructive of the bone-to-implant in- 43 terface and thus, cannot be used for longitudinal measures. It has a limited role in a clinical setting. The final invasive method for evaluating secondary stability is the pullout test. A pullout test measures the force required to pull an implant out of bone. applied parallel to the long axis of the screw. A force is This force is increased until the screw looses its holding power and comes out of the bone. This common test has been used in orthopedics,142,143 otolaryngology,144 dental implants145 and orthodontics.47 Using MSIs Huja et al. showed that pullout forces are different for different areas of the mouth, indicating that bone quality is not homogeneous.47 Salmória and co-workers concluded from their work that pullout is a more efficient measure of secondary stability than insertion torque because insertion torque could not be used to predict MSI success.44 without limitations. This measurement technique is not It is destructive of the implant tis- sue interface and thus, cannot give longitudinal measurements. It cannot be used clinically and is limited to lab experiments. While all these invasive methods to measure implant stability yield valuable information, they are all destructive and consequently, for a given implant, can provide one 44 measurement. This limits their ability to yield informa- tion about the healing and stability of a single implant. Non-Invasive Methods Non-invasive methods to measure implant stability differ from invasive methods by virtue of the fact that the use of these measurements does not disturb the bone/implant interface. Consequently, they can be used to study the changes in stability of individual implants over time. Radiographic x-rays were the first non-invasive technique used to evaluate implant stability. Hermann et al. described how the technique of taking successive bitewing radiographs could be used to evaluate the height of crestal bone around dental implants.146 Goodson and co-workers re- ported that radiographs could be used to determine changes in bone density surrounding dental implants.147 However, they found that the technique can only be used to detect changes if the decrease in mineral density is 40% or greater.147 These radiographic techniques may not be useful to evaluate MSIs. Miniscrews are rarely oriented in the same direction as dental implants, so bitewings cannot be used to evaluate bone level. To evaluate changes over 45 time, radiographs must be standardized or they can become distorted and are not useful. Another method to evaluate implant stability in a noninvasive manner is the use of finite element analysis models. Finite element analysis utilizes computer-generated simulations that are employed to evaluate properties of bone and its stresses. It is a theoretical analysis based on the properties of the material being studied, including Young’s modulus of elasticity, Poisson ratio, bone density and PDL properties. Each of these variables is estimated by the investigator and used by the computer to determine the behavior of the material in question. Consequently, if the value of these variables is not correct the model may yield an incorrect or misleading result. Finite element analysis has been used to evaluate stresses and strains in bone surrounding implants in different situations. For ex- ample, by altering the characteristics of bone surrounding the implant, finite element modeling can assess stresses and strains that would theoretically be present.148,149 method has been used to study MSIs. This Dalstra et al. studied the effect of cortical bone density on stress distribution around MSIs.31 They showed that during tipping, stresses are concentrated in the cortical region of the bone and that implant length and diameter are important in determin46 ing stresses felt by the bone. Miyajima and colleagues studied the effect of MSI size and direction of applied force on stress distribution.30 They found that large and small screws had similar stress/strain patterns but stress and strain were higher for the smaller screw when the same magnitude of force was applied.30 They also discovered that a more horizontal force produced greater stress in the bone, while vertical force application distributed the stress over a larger area.30 As with the other methods, fi- nite element analysis has some limitations. It is purely a theoretical and static evaluation and thus, may be limited in its clinical usefulness. It also often assumes a homo- geneous bone quality surrounding the implant, which likely is not the case in biological subjects. Its mathematical modeling is based on several assumptions. Consequently, if those assumptions are incorrect, the model will be wrong and potentially misleading. Percussion testing is a method of determining implant stability that is based on the sound the implant makes when percussed clinically. A solid object, usually a mirror handle, is used to strike the implant and the sound elicited is subjectively evaluated by the practitioner to get a feel for the stability of the implant. This method is sub- jective and nearly impossible to standardize and so has 47 little usefulness as a reliable measure of implant stability. The impact hammer method of evaluating implant stability is simply an improved percussion test. It attempts to limit the subjectivity of the parameters of the percussion test by using microphones, accelerometers and computer processing of the detected signal. This method operates on a principle similar to a tuning fork. mer strikes an object (an implant). at its natural frequency. quency. A small impact hamThat object vibrates A microphone detects the fre- This information is converted into useful informa- tion, such as, stability measurements. The Dental Checker, an impact hammer method of stability evaluation, developed by Aoki and Hirakawa, was used by Elias et al. to detect tooth mobility by converting tooth rigidity into an acoustic signal.150 The Periotest was developed as a more elabo- rate version of the Dental Checker. It uses an electromag- netically controlled tapping rod with an accelerometer to produce and evaluate implant stability. It has been shown to be a reliable method of determining implant stability.151,152 However, several reports indicate that, while ef- fective for use with natural teeth, it may lack sensitivity to adequately determine changes in implant stability.152,153 Natural teeth have a large range of mobility, with Perio48 test readings ranging from -8 to +50.151 much more narrow range (-5 to +5).151 Implants have a Clinically, osseoin- tegrated implants have an even smaller range (-4 to +2).154,155 Consequently, the sensitivity of the Periotest for implants has been called into question. This technique has been shown to be very sensitive to position and orientation.156 Meredith et al. have shown that Periotest meas- urements can vary by 1.5 units for every millimeter from the marginal bone the striking point changes.153 However, Lachmann and co-workers showed that, when used appropriately, this method could identify peri-implant bone loss in millimeter increments.157 The Periotest has been used to evaluate the stability of miniscrews. Maria and colleagues used the Periotest to show that neither length nor diameter influences primary stability.158 The limitations of the Pe- riotest, lack of sensitivity and susceptibility to operator error, have been criticized in work performed by Salvi and Lang.159 Another non-invasive method to evaluate implant stability using vibration is the pulsed oscillation technique. It is a system introduced by Koneko et al. that uses an electric pulse generator connected to a piezoelectric element that causes a needle to vibrate.160 when the needle touches the implant it causes the implant to vibrate. 49 A second needle attached to a piezoelectric element records resonance vibrations generated from the bone/implant interface. This converts the bone/implant vibration into an electric signal that is then evaluated by an oscilloscope. The sensitivity of this device is dependent on the orientation of the needle, as well as its load and position. This method has been shown to have a low sensitivity for the assessment of implant rigidity.161 Resonance Frequency Analysis Resonance frequency analysis is a method used to determine implant stability based on vibrations of the implant within bone. According to resonance frequency the- ory, any object has a tendency to oscillate at larger amplitudes for certain frequencies. Resonance frequency analysis uses this concept to excite a dental implant or MSI by some mechanical means and then measures the oscillation pattern of the implant/bone complex in order to determine the stability of the implant in bone. For any physi- cal system there can be multiple modes of vibration. For a dental or orthodontic implant this means that it can vibrate in three different ways. These include rotational, horizontal and vertical vibration (Figure 2.2). 50 Figure 2.2:Implant modes of vibration The actual overall vibration is always a combination or mixture of the three modes. However, they may not all be excited to the same degree. For example, if a force is applied in a direction perpendicular to the long axis of the implant, then the horizontal mode of vibration will be the predominant type. In this way the variability of the system can be minimized. Minimizing two of the modes of vibration by controlling the direction of force application, allowing the measurement of the third predominant type, can yield valuable information about the stability of the implant (Figure 2.3). 51 Figure 2.3: Minimizing implant modes of vibration For the measurement of implant stability in bone, a horizontal force that is perpendicular to the long axis of the implant is used. This direction is employed because it is the easiest and most predictable direction to apply a force to an implant clinically. Consequently, it is also the most common direction that a MSI is loaded for orthodontic use. By minimizing implant vibration in the rota- tional and vertical direction, the system of implant and bone can be treated as a cantilever beam. The following formula is used to determine the resonance frequency of the implant in the horizontal direction.162 52 Where Rf is the resonance frequency, E=Young’s Modulus of elasticity, I=Moment of inertia of the beam (determined by the shape of the beam),163 l=length of the beam and m=mass of the beam. Each of these variables, in any given system, is a constant defined by the implant and the surrounding bone except Young’s modulus. It is this variable that allow the use of resonance frequency to evaluate the stability of the implant. Theoretically as the modulus of elasticity of the bone, i.e. stiffness, increases, the resonance frequency of the implant increases. The two share a direct relationship. Resonance frequency devices utilize the property that the vibration of any system, in this case implants, creates sound waves. Measurements of resonance frequency are actu- ally measurements of sound waves that are generated by the vibrating implant.164 Because there are so many variables that determine the resonance frequency of a system, single measurements yield limited clinical information about osseointegration. In order to evaluate osseointegration, se- quential measurements are required.165 53 Resonance frequency has been used to evaluate various properties of the bone/implant interface. Huang et al. used a device called the Iplomates to evaluate the relationship between the height of and force of clamping of an implant and its resonance frequency.166 They found that resonance frequency levels correlated with the clamping level and the magnitude of the clamping force. As clamping level increased (more implant out of the device), resonance frequency decreased. As the force used to clamp the im- plant increased, resonance frequency increased. In another study, Huang and co-workers used finite element analysis to evaluate the effect of marginal bone density, type and level on the resonance frequency of an implant.167 They showed that resonance frequency is determined, at least theoretically, by each of these factors. Others have also used the Iplomates device to evaluate implants. Chang et al. evaluated resonance frequency of dental implants. They found that the technique could yield information about bone-implant union during the healing process.168 This two-part study first evaluated the reso- nance frequencies taken over 12 weeks after implant placement and then compared them to in vitro values obtained in the lab by increasing clamping torque of the same type of implant. They concluded that resonance frequency might be 54 helpful in determining the healing status of an implant. The Iplomates devices is not without its disadvantages. The major disadvantage of the technique is when an implant is excited by tapping with a hammer, which is the case with the Iplomates device, the implant oscillates in all three modes of vibration. The magnitude of each mode is deter- mined by the nature of the impact, i.e. direction and point of impact. It is important to restrict the oscillation to the first mode, which is the mode that is perpendicular to the long axis of the implant because this will yield the most applicable clinical results.169 The Osstell Mentor device has also been used to evaluate stability in dental implants.164,170 Instead of using hammer impaction to excite the implant, a sinusoidal electromagnetic signal is used. This is the traditional method of measuring natural frequencies and their corresponding dampening factors.169 The Osstell device uses a transducer, located in a clinical handpiece, that is attached to a computer. This transducer produces the electromagnetic sig- nal that causes the implant to vibrate. This vibration is produced when a metal peg with a small magnet attached to its top is screwed into the implant and excited by the electromagnetic signal. The sinusoidal signal is produced in a range from 1 kHz to 15 kHz frequencies. The vibration 55 that produces the largest amplitude is the implants natural resonance frequency. This resonance vibration of the im- plant is sensed by a second transducer, located in the same hand piece. Its frequency is reported and used to deter- mine the stability of the implant. Due to the method of implant vibration, the Osstell device actually measures the frequency of the vibration in hertz. The nature of the electromagnetic signal used to elicit implant vibration may actually cause vibration in two horizontal directions simultaneously, which are approximately perpendicular to each other. Consequently, for each measurement event two reso- nance frequencies may be detected and recorded, each yielding information about the nature of the bone-to-implant interface in their respective direction. The third genera- tion Osstell Mentor device reports all measurements in units termed implant stability quotient (ISQ) and not hertz, which is the units of actual measurement. The ISQ is based on the underlying resonance frequency and ranges from 1 (lowest stability) to 100 (highest stability). The Os- stell device is pre-calibrated so that the ISQ values are valid for only a single type of implant.171 Consequently, if the transducer has not been pre-calibrated for a particular type of implant, then comparisons to other types of implants cannot be made.171 One clinically important factor 56 that can influence the resonance frequency measurements taken by the Osstell device is the transducers orientation in relation to the implant. The manufacturer suggests that the orientation should be perpendicular to the long axis of the implant (Figure 2.4). Because the orientation can af- fect the measurement of resonance frequency, it is important to standardize the orientation when taking sequential measurements.164,171,172 When the orientation is standardized, reliability of the measurements has been shown to be excellent in a clinical environment.173 The Osstell device has been shown to be more precise than the Periotest device for evaluating implant stability in the clinical (intraclass coefficients for implant stability were 0.99 for the Osstell Mentor and 0.88 for the Periotest)173 and laboratory (intraclass coefficients for implant stability were 0.99 for the Osstell Mentor and 0.86 for the Periotest)174 environment. This is due to the sensitivity of the Periotest to operator error during use. 57 Figure 2.4: Orientation of Osstell Mentor transducer during measurements. Adapted from Osstell Mentor picture library.175 Several studies illustrate the effect that the bone surrounding the implant has on the resonance frequency. Ito et al. suggested in an in vitro study that the marginal or cortical bone plays the most important role in implant stability.176 This is in agreement with work done by Rod- rigo and co-workers, who reported higher resonance frequencies in specimens where the cortical bone had been preserved than in specimens when it was eliminated.177 Finite element models developed by Deng et al. also predicted higher resonance frequencies when more coronal bone was deposited during osseointegration.178 Other studies have shown correlations between resonance frequency analysis and other measures of implant sta58 bility. Boronat López et al. demonstrated a significant correlation between resonance frequency and insertion torque.179 This was in agreement with work by Turkyilmaz and colleagues.180 They also showed positive correlations with resonance frequency and bone density. This is in con- trast to a study where no correlations were found between resonance frequency, bone density and insertion torque.181 Relationships between histomorphometric measurements and resonance frequency have also been examined. Zhou et al. were able to show that increased bone-to-implant contact was correlated to a higher implant stability quotient.182 This was also shown in work performed by Scarano and coworkers.183 Using different types of implants, Kim et al. found ISQ and bone-to-implant contact increased during the first eight weeks after placement for all groups tested.184 Researchers have also studied the use of resonance frequency to predict implant failure and other aspects of implant stability. Scarano et al. demonstrated that an ISQ below 36 could be used to identify failed dental implants.185 Others have used resonance frequency to deter- mine the best time to load implants.186 Some have used resonance frequency to identify good sites for implant placement based on initially stability.187 59 A number of studies have brought into question the usefulness of resonance frequency in determining implant stability due to the failure to demonstrate correlations between resonance frequency, cutting torque, marginal bone levels, timing of loading, bone-to-implant contact and changes of stability over time.121,172,181,188-190 However, sub- stantial literature exists that supports this method for evaluating dental implant stability but only limited literature demonstrating its efficacy in measuring miniscrew implant stability is available. Using a third generation Osstell Mentor device, Katsavrias, showed that the device was reliable when measuring miniscrew implants with a length of 11 mm and an external diameter of 1.6 mm placed in synthetic bone.130 He showed intraclass correlation for multiple measurements ranging from 0.953 to 0.992, and single measure correlation ranging from 0.870 to 0.977. He also demonstrated signifi- cant differences between different densities of synthetic bone. In an in vitro study, Veltri et al. showed that resonance frequency could be used for different types of miniscrew implants.191 They concluded that it was an ac- ceptable technique to assess primary stability of MSIs in bone and that the three different MSI systems in the study showed similar results. 60 Summary The use of miniscrews for skeletal anchorage in orthodontics has the potential to improve the treatment of certain types of malocclusions. However, MSI failures will greatly influence the efficiency and efficacy of treatment. 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Morris HE, Ochi S, Crum P, Orenstein I, Plezia R. Bone density: its influence on implant stability after uncovering. J Oral Implantol 2003;29:263-269. 155. Teerlinck J, Quirynen M, Darius P, van Steenberghe D. Periotest: an objective clinical diagnosis of bone apposition toward implants. Int J Oral Maxillofac Implants 1991;6:55-61. 156. Schulte W, Lukas D. The Periotest method. Int Dent J 1992;42:433-440. 157. Lachmann S, Laval JY, Jäger B, Axmann D, Gomez-Roman G, Groten M, Weber H. Resonance frequency analysis and damping capacity assessment. Part 2: peri-implant bone loss follow-up. An in vitro study with the Periotest and Osstell instruments. Clin Oral Implants Res 2006;17:80-84. 158. Maria O, Ana M, Andreu P. Primary stability of microscrews based on their diameter, length, shape and area of insertion. an experimental study with Periotest. Prog Orthod 2008;9:82-88. 159. Salvi GE, Lang NP. Diagnostic parameters for monitoring peri-implant conditions. Int J Oral Maxillofac Implants 2004;19 Suppl:116-127. 160. Kaneko T, Nagai Y, Ogino M, Futami T, Ichimura T. Acoustoelectric technique for assessing the mechanical state of the dental implant-bone interface. J Biomed Mater Res 1986;20:169-176. 161. Kaneko T. Pulsed oscillation technique for assessing the mechanical state of the dental implant-bone interface. Biomaterials 1991;12:555-560. 76 162. Meredith N, Alleyne D, Cawley P. Quantitative determination of the stability of the implant-tissue interface using resonance frequency analysis. Clin Oral Implants Res 1996;7:261-267. 163. Pilkey WD. Analysis and Design of Elastic Beams. New York: John Wiley & Sons, Inc.; 2002. 164. Sennerby L, Meredith N. Implant stability measurements using resonance frequency analysis: biological and biomechanical aspects and clinical implications. Periodontol 2000 2008;47:51-66. 165. Aparicio C, Lang NP, Rangert B. Validity and clinical significance of biomechanical testing of implant/bone interface. Clin Oral Implants Res 2006;17 Suppl 2:2-7. 166. Huang HM, Pan LC, Lee SY, Chiu CL, Fan KH, Ho KN. Assessing the implant/bone interface by using natural frequency analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:285-291. 167. Huang H, Lee S, Yeh C, Lin C. Resonance frequency assessment of dental implant stability with various bone qualities: a numerical approach. Clin Oral Implants Res 2002;13:65-74. 168. Chang W, Lee S, Wu C, Lin C, Abiko Y, Yamamichi N, Huang H. A newly designed resonance frequency analysis device for dental implant stability detection. Dent Mater J 2007;26:665-671. 169. Meredith N. A review of nondestructive test methods and their application to measure the stability and osseointegration of bone anchored endosseous implants. Crit Rev Biomed Eng 1998;26:275-291. 170. Garg AK. Osstell Mentor: measuring dental implant stability at placement, before loading, and after loading. Dent Implantol Update 2007;18:49-53. 171. Pattijn V, Jaecques SVN, De Smet E, Muraru L, Van Lierde C, Van der Perre G, Naert I, Vander Sloten J. Resonance frequency analysis of implants in the guinea pig model: influence of boundary conditions and orientation of the transducer. Med Eng Phys 2007;29:182-190. 77 172. Veltri M, Balleri P, Ferrari M. Influence of transducer orientation on Osstell stability measurements of osseointegrated implants. Clin Implant Dent Relat Res 2007;9:60-64. 173. Zix J, Hug S, Kessler-Liechti G, Mericske-Stern R. Measurement of dental implant stability by resonance frequency analysis and damping capacity assessment: comparison of both techniques in a clinical trial. Int J Oral Maxillofac Implants 2008;23:525-530. 174. Lachmann S, Laval JY, Jäger B, Axmann D, Gomez-Roman G, Groten M, Weber H. Resonance frequency analysis and damping capacity assessment. Part 2: peri-implant bone loss follow-up. An in vitro study with the Periotest and Osstell instruments. Clin Oral Implants Res 2006;17:80-84. 175. Osstell - Downloads Osstell Mentor. Available at: http://www.osstell.com/?id=3043 [Accessed September 30, 2009]. 176. Ito Y, Sato D, Yoneda S, Ito D, Kondo H, Kasugai S. Relevance of resonance frequency analysis to evaluate dental implant stability: simulation and histomorphometrical animal experiments. Clin Oral Implants Res 2008;19:9-14. 177. Andrés-García R, Vives NG, Climent FH, Palacín AF, Santos VR, Climent MH, Bullón P. In vitro evaluation of the influence of the cortical bone on the primary stability of two implant systems. Med Oral Patol Oral Cir Bucal 2009;14:E93-97. 178. Deng B, Tan KB, Liu GR, Lu Y. Influence of osseointegration degree and pattern on resonance frequency in the assessment of dental implant stability using finite element analysis. Int J Oral Maxillofac Implants 2008;23:1082-1088. 179. Boronat-López A, Peñarrocha-Diago M, MartínezCortissoz O, Mínguez-Martínez I. Resonance frequency analysis after the placement of 133 dental implants. Med Oral Patol Oral Cir Bucal 2006;11:E272-276. 180. Turkyilmaz I, Sennerby L, McGlumphy EA, Tözüm TF. Biomechanical aspects of primary implant stability: A human cadaver study. Clin Implant Dent Relat Res 2008. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18422713 [Accessed May 19, 2009]. 78 181. Schliephake H, Sewing A, Aref A. Resonance frequency measurements of implant stability in the dog mandible: experimental comparison with histomorphometric data. Int J Oral Maxillofac Surg 2006;35:941-946. 182. Zhou Y, Jiang T, Qian M, Zhang X, Wang J, Shi B, Xia H, Cheng X, Wang Y. Roles of bone scintigraphy and resonance frequency analysis in evaluating osseointegration of endosseous implant. Biomaterials 2008;29:461-474. 183. Scarano A, Degidi M, Iezzi G, Petrone G, Piattelli A. Correlation between implant stability quotient and boneimplant contact: a retrospective histological and histomorphometrical study of seven titanium implants retrieved from humans. Clin Implant Dent Relat Res 2006;8:218-222. 184. Kim SK, Lee HN, Choi YC, Heo S, Lee CW, Choie MK. Effects of anodized oxidation or turned implants on bone healing after using conventional drilling or trabecular compaction technique: histomorphometric analysis and RFA. Clin Oral Implants Res 2006;17:644-650. 185. Scarano A, Carinci F, Quaranta A, Iezzi G, Piattelli M, Piattelli A. Correlation between implant stability quotient (ISQ) with clinical and histological aspects of dental implants removed for mobility. Int J Immunopathol Pharmacol 2007;20:33-36. 186. West JD, Oates TW. Identification of stability changes for immediately placed dental implants. Int J Oral Maxillofac Implants 2007;22:623-630. 187. Seong W, Holte JE, Holtan JR, Olin PS, Hodges JS, Ko C. Initial stability measurement of dental implants placed in different anatomical regions of fresh human cadaver jawbone. J Prosthet Dent 2008;99:425-434. 188. da Cunha HA, Francischone CE, Filho HN, de Oliveira RCG. A comparison between cutting torque and resonance frequency in the assessment of primary stability and final torque capacity of standard and TiUnite single-tooth implants under immediate loading. Int J Oral Maxillofac Implants 2004;19:578-585. 189. Ostman P, Hellman M, Sennerby L. Direct implant loading in the edentulous maxilla using a bone density-adapted 79 surgical protocol and primary implant stability criteria for inclusion. Clin Implant Dent Relat Res 2005;7 Suppl 1:S60-69. 190. Huwiler MA, Pjetursson BE, Bosshardt DD, Salvi GE, Lang NP. Resonance frequency analysis in relation to jawbone characteristics and during early healing of implant installation. Clin Oral Implants Res 2007;18:275-280. 191. Veltri M, Balleri B, Goracci C, Giorgetti R, Balleri P, Ferrari M. Soft bone primary stability of 3 different miniscrews for orthodontic anchorage: a resonance frequency investigation. Am J Orthod Dentofacial Orthop 2009;135:642648. 80 CHAPTER 3: JOURNAL ARTICLE Abstract Purpose: This study evaluated changes in miniscrew implant (MSI) stability over eight weeks using resonance frequency analysis. The study was designed to evaluate the impact of pilot holes and placement sites on changes in stability. Method: Implant Stability Quotient (ISQ) values were measured using the Osstell® Mentor device for 22 MSIs, 1.6 mm in diameter and 9 mm in length, placed in the maxilla of adult beagle dogs (20 months old). Measurements were taken weekly, starting at the time of placement and ending at eight weeks. Using a split mouth design, 1.1 mm wide pilot holes were randomly selected and drilled to a depth of 3 mm for half of the MSIs prior to placement. MSI placement was also divided between keratinized and non-keratinized tissue. Results: Nine of the 22 MSIs failed; all of the failures were related to having been placed in nonkeratinized tissue. MSIs that failed showed significantly (p<0.05) higher decreases in stability during the first three weeks than the MSIs that remained stable. MSIs that remained stable throughout the study also showed decreases in stability during the first three weeks and increases in stability between the third and fifth week (p<0.05). Pilot 81 holes had little or no effect (p>0.05) on MSI stability. Conclusion: Stability of MSIs decreases from week one to week three and increases from week three to week five. Pilot holes do not affect the stability of MSIs. Placement of MSIs into non-keratinized tissue negatively impacts their stability and increases the likelihood of failures. Introduction One of the challenges facing orthodontics is the control of unwanted tooth movement. Minimizing unwanted tooth movement has been an important objective of orthodontists since the beginning of the specialty. Recently, miniscrew implants (MSIs) have become a popular means of skeletal anchorage to selectively control tooth movement. However, the increased use of MSIs has revealed a substantial number of failures. Reported success rates range from less than 50% to over 95%.1-5 The unpredictability of MSIs limits their usefulness as a treatment modality. There are a number of factors that may cause MSI failure including, mobility,6-8 excessive heating of the bone during placement,9-11 placement in keratinized vs. nonkeratinized soft tissue,1,2 host factors such as uncontrolled diabetes,12 excessive loading13,14 and poor oral hy- 82 giene.1 The primary cause of MSI failures is the loss of bone-to-implant contact or stability. Stability includes primary stability, which is a mechanical interlocking between the implant and surrounding bone directly after placement, and secondary stability, which pertains to remodeling and healing of bone surrounding the implant.15 The overall or total stability of a MSI represents a combination of primary and secondary stability (Figure 3.1). Figure 3.1: Primary, secondary and total stability curves over eight weeks. Adapted from Raghavendra et al.15 Understanding changes in MSI stability over time could lead to the development of clinical management techniques that promote faster healing improving primary or secondary 83 stability (Figure 3.2). Our understanding of MSI stability is limited by our lack of ability to measure stability in vivo. Figure 3.2: The effect on total stability of a shift in secondary stability. Adapted from Raghavendra et al.15 The stability of MSIs has been previously measured using insertion torque,3,16 removal torque,17,18 histological studies19,20 and pullout tests.21 Because these measures re- quire the destruction of the bone-to-implant interface, they are not useful for clinical application. The most promising non-invasive method to measure implant stability is resonance frequency, which has been successfully used to study the stability over time of dental implants used in clinical situations.22-24 84 Resonance frequency analysis determines implant stability by measuring vibrations of the implant within bone.25,26 The stiffer the bone surrounding the implant, the higher the frequency of the measured vibration. Because this measurement is dependent on the quality of the bone surrounding the implant, it is used as a proxy for the stability of the implant. Since this method does not disturb implant/bone interface, it can be used to evaluate changes in stability of an implant over time. Changes in stability during the first few weeks after placement have been evaluated in the dental implant literature using resonance frequencies. Based on 122 dental implants placed in humans, Ersanli et al. showed decreases in stability during the first three postsurgical weeks and increases in stability between three and six weeks and six weeks and six months.24 Balshi et al. used monthly evalua- tions of 276 dental implants to show a decrease in stability during the first month and increases during the second and third months.22 Barewal et al., who evaluated changes in dental implant stability according to bone type, found a decrease in stability during the first three weeks and an increase from week three to week six.27 While the pattern of an initial decrease in stability followed by an increase 85 has been established for dental implants, the pattern of stability for MSIs remains unknown. The purpose of this study was to determine the longitudinal changes in MSI stability that occur over the first eight weeks after placement. Secondary aims of the study were to evaluate the effect of pilot holes and placement site (keratinized vs. non-keratinized tissue) on early MSI stability. Materials and Methods Animals The sample included two healthy male, 20 month-old beagle dogs (approximate weight 15 kg). Starting 1 week prior to MSI placement, the dogs were maintained on a soft diet (Canidae® Lamb and Rice canned food, Canidea Corporation, San Luis Obispo, CA; 5006 Canine Diet [Hard kibble mixed with warm water], PMI Nutrition International, LLC., Brentwood, MO). The animals were housed separately in the Comparative Medicine Department of Saint Louis University Medical School. All procedures were approved by the Saint Louis University Animal Care Committee (Authorization #2010). 86 MSI Placement The dogs were administered 25 mg/kg of Enrofloxacin (Baytril, Bayer Health Care, LLC., Animal Health Division, Shawnee Mission, KS) intravenously during implant placement as a prophylactic measure and intramuscularly for two days post-surgery. Carprofen (Rimadyl, Pfizer Animal Health, Exton, PA) was administered at the rate of 4mg/kg subcutaneously as an analgesic. Induction of general anesthesia was accomplished by the intravenous administration of Propofol (Propofol, Abbot Animal Health, North Chicago, IL) 7mg/ml. Maintenance was achieved by 2-3% isoflurane (Aer- rane, Baxter Healthcare Corporation, Deerfield, IL). An IV drip of 0.9% sodium chloride (Hospira, Inc., Lake Forest, IL) administered at a rate of 12ml/kg/hr, was given to maintain hydration. Postoperatively, the animals were given Acepromazine Maleate (VEDCO, Inc., St. Joseph, Mo) 0.2ml IV to calm post anesthetic excitement. Before MSI placement, lateral head films were taken to determine the best sites for MSI placement. Sites were chosen based on the availability of comparable sites in the same location on the opposite side of the maxilla. For the first dog, 10 insertion sites were identified; 12 insertion sites were identified for the second dog. One screw of each matched right and left side pair was randomly selected 87 to receive a pilot hole prior to MSI placement. All MSIs were placed in the maxillary premolar region apical to the furcations (Figure 3.3). Dog A Right Left = No pilot hole = Pilot hole Dog B = non-Keratinized = Keratinized Right Left Figure 3.3: MSIs in Dog A and Dog B by location with pilot hole and soft tissue information. Ten MSIs (five per side) were placed apical to the root tips in non-keratinized tissue; the MSIs occlusal to the root tips were placed in keratinized gingiva. Placement sites were swabbed with 0.12% chlorhexidine gluconate (Acclean®, Henry Schein, Inc., Melville, NY). To aid in visu- alizing the placement site and prevent soft tissue compli- 88 cations, a 3.0 mm tissue punch (Premier Medical Products, Plymouth Meeting, PA) was performed. MSIs that had been randomly chosen to receive a pilot hole were drilled at 1000 r.p.m., using a Brasseler lab hand piece (uP501 and UG33, Brassler USA®, Savannah, GA) (Figure 3.4) and constant irrigation with sterile saline solution (Braun Medical Inc., Irvine, CA). Pilot holes were drilled using a 1.1 mm diameter drill (Sendax Spiral Drill, Imtec Corporation, Ardmore, OK) with an endo stop placed at a distance of 3 mm from the tip, held in place with flowable composite (Henry Schein®, Melville, NY) (Figure 3.5). Figure 3.4: Brassler handpiece. Figure 3.5: Pilot hole drill. MSIs were placed using a hand driver (Ancoragem Ortodontica, Neodent®, Curitiba, Brazil) until the head of the screw was within 0.5 mm of the cortical bone. After placement, lat- eral head films were taken to verify that the roots had not been contacted. 89 Miniscrew Implants MSIs used in this study were Ancoragem Ortodontica screws manufactured by Neodent® (Curitiba, Brazil). These cylindrical shaped screws were 9 mm long, with an external diameter of 1.6 mm, an internal diameter of 1.1 mm, and a pitch of 0.7 mm. The head of the screw had been modified to include a 1.1 mm internal thread that accepts the Osstell® Mentor Smartpeg type A3 (Figure 3.6, 3.7 and 3.8). Figure 3.6: MSI side and top view. Figure 3.7: Smartpeg. Figure 3.8: MSI and Smartpeg connected. Resonance Frequency Measurements After MSI placement, the Osstell® Smartpeg type A3 (Osstell®, Göteborg, Sweden) was placed into the head of the screw and tightened with finger pressure according to the manufacturer’s instructions. Using the Osstell® Mentor transducer, two sets of measurements were taken for each 90 screw. The first set of measurements was made parallel to the maxillary occlusal plane. The second set of measurements was made perpendicular to the maxillary occlusal plane (Figure 3.9). All resonance frequencies were taken perpendicular to the long axis of the screw and attached Smartpeg (Figure 3.10), and were reported as implant stability quotients (ISQs). Figure 3.9: Orientation of Osstell® transducer in relation to the occlusal plane. Figure 3.10: Orientation of Osstell® transducer in relation to the Smartpeg and MSI. Adapted from Osstell® Mentor picture library.28 91 Using the same methodology, resonance frequency measurements were taken at weekly intervals for eight weeks after placement of the implants. The previously described proce- dures were used to place the dogs under general anesthesia for each of the measurements occasions. Statistical Analysis Success for this study was defined as lack of MSI pullout. Due to the number of failures that occurred after three weeks, two sets data were evaluated, including 1) all the MSIs available during the first three weeks, and 2) only those MSIs that remained intact throughout the eight weeks of the study. Wilcoxon signed-rank tests were used to evaluate differences in ISQ between screws that 1) received a pilot hole and those that did not, 2) were placed in keratinized gingiva and those placed in non-keratinized gingival, and 3) failed and those that did not. Wilcoxon signed-rank tests were also used to evaluate changes in average ISQ between each successive time point from surgery to eight weeks post insertion. All Statistical testing was calcu- lated using SPSS Version 17.0 (SPSS Incorporated, Chicago, IL). 92 Results Failures A large number of failures occurred during the study. Of the 22 MSIs that were placed, nine (41%) failed at some point during the study (Figure 3.11). MSIs failed at week three (four failures), week five (two failures), week six (two failures), and week eight (one failure). All of the MSIs that failed had been placed into non-keratinized tissue. ISQ readings could not be taken on one MSI after ini- tial measurement due to a mechanical failure of the internal threading of the head. All of the failures occurred while attempting to unscrew the Smartpeg from the MSI; the MSI unscrewed from the bone before the Smartpeg loosened. ISQ values and descriptive statistics for all screws present are found in Table 3.1. 93 Figure 3.11: Timing of MSI posterior location, tissue †This screw had mechanical week one. *This screw failed in week Table 3.1. Number Mean Std. Dev. Min-Max Number Mean Std. Dev. Min-Max failures by dog, anteriortype and pilot hole presence. failure of internal threading in eight. Weekly ISQ values from placement to eight weeks. T0 22 32.3 7.9 18-45 T1 21 30.2 8.0 17-42 All MSIs until failure T2 T3 T4 T5 21 21 17 17 26.7 25.0 26.4 26.2 7.7 8.3 5.4 6.2 12-39 9-42 14-36 15-34 T6 15 26.3 4.3 16-32 T7 13 27.0 4.6 16-32 T8 13 27.7 4.7 16-33 T0 12 30.9 9.4 18-45 MSIs surviving the entire study T1 T2 T3 T4 T5 12 12 12 12 12 30.3 27.8 26.0 26.7 27.7 9.0 6.9 5.7 5.3 5.0 17-42 15-38 14-32 14-33 15-33 T6 12 26.7 4.2 16-32 T7 12 26.8 4.8 16-32 T8 12 27.4 4.8 16-33 94 Comparison of ISQ Changes of all MSI Over the First Three Weeks of the Study Descriptive statistics and statistical comparisons for the first three weeks and adjusted to baseline are found in Table 3.2 and 3.3. Table 3.2: Descriptive statistics and statistical comparisons (Wilcoxon signed-rank test) of ISQ values between MSIs that Failed vs. Survived, MSIs that receieved a Pilot hole vs. no Pilot hole and MSIs placed in Keratinized vs. non-Keratinized tissue from surgery (T0) to three weeks (T3). Group T0 T1 T2 T3 Failed Mean 34.2 30.3 25.6 24 Std. Dev. 5.7 7.0 8.7 10.8 Survived Mean 31.2 30.4 28.1 26.1 Std. Dev. 9.4 9.0 7.0 5.7 p-value 0.100 0.455 0.944 0.701 Pilot hole Mean Std. Dev. No Pilot hole Mean Std. Dev. p-value 32.6 7.9 30.2 8.0 27.9 8.2 25.7 9.8 32.5 8.3 0.674 30.6 8.3 0.373 26.0 7.5 0.443 24.6 6.8 0.160 27.2 6.6 25.6 5.6 26.7 9.0 0.807 24.7 10.5 0.675 Keratinized Mean 30.2 29.8 Std. Dev. 9.3 9.2 non Keratinized Mean 34.8 30.9 Std. Dev. 5.8 6.9 p-value 0.100 0.455 *significant at the !=0.05 level There were no significant differences in ISQs at any time point during the first three weeks between the MSIs that eventually failed and those that did not. There also were no significant difference during the first three weeks 95 between those that had pilot holes and those that did not, or between those that were place in keratinized or nonkeratinized tissues (Figure 3.12, 3.13 and 3.14). Figure 3.12: ISQ over the first three weeks of failed and survived MSIs. No time points statistically significant at the p-value 0.05 level. Figure 3.13: ISQ over the first three weeks for pilot vs. no pilot hole MSIs. No time points were statistically significant at the p-value 0.05 level. 96 Figure 3.14: ISQ over the first three weeks for keratinized vs. non-keratinized placement of MSIs. No time points were statistically significant at the p-value 0.05 level. Table 3.3. Descriptive statistics and statistical comparisons (Wilcoxon signed-rank test) of changes in ISQ from surgery (T0) to three weeks (T3). Group T0-T1 T0-T2 T0-T3 Failed Mean -3.9 -8.6 -10.2 Std. Dev. 2.6 6.5 9.0 Survived Mean -0.8 -3.1 -5.1 Std.Dev. 1.6 3.7 4.6 p-value 0.001* 0.009* 0.032* Pilot hole Mean Std. Dev. No Pilot hole Mean Std.Dev. p-value -1.9 2.5 -6.5 5.9 -7.9 6.1 -2.5 2.9 0.084 -4.7 5.8 0.201 -6.9 8.6 0.168 Keratinized Mean -0.5 -3.1 Std. Dev. 1.3 3.8 non-Keratinized Mean -3.9 -8.1 Std.Dev. 2.5 6.4 p-value 0.001* 0.013* *significant change at the !=0.05 level 97 -4.7 4.7 -10.1 8.6 0.037* The changes in ISQ values that occurred over the first three weeks were significantly different between the MSIs that failed and those that did not. After the first week, the MSI that eventually failed showed significantly greater decreases in ISQ than those that did not. The differences between the MSI that failed and those that did not increased significantly, from 0.8 to 5.1, over the first three weeks. While the changes were also greater for MSI with pilot holes than for those without pilot holes, the differences were not statistically significant. In con- trast, MSIs placed in non-keratinized tissue showed significantly greater decreases in ISQ values over the first three weeks than MSI place in keratinized tissue (Figure 3.15, 3.16 and 3.17). Figure 3.15: Change in ISQ over time for MSIs that failed and survived over the first three weeks. Changes at T1, T2 & T3 were statistically significant. 98 Figure 3.16: Change in ISQ over time for MSIs with pilot hole and no pilot hole over the first three weeks. No significant changes were found. Figure 3.17: Change in ISQ over time for MSIs placed in keratinized and non-keratinized tissue over the first three weeks. Changes at T1, T2 & T3 were statistically significant. 99 Longitudinal Changes in ISQ of MSIs Maintained Throughout the Study While the ISQ values decreased during the first week, the changes were small and not statistically significant (Table 3.4). Statistically significant decreases in ISQ were found during the second (T1-2) and third weeks (T2-3). Significant increases occurred during the fourth (T3-4) and fifth (T4-5) weeks. The decrease in ISQ values that oc- curred during the sixth week, as well as the increases that occurred during the seventh, eighth and ninth weeks were not statistically significant (Figure 3.18). ISQ values at week eight were lower than ISQ values at MSI placement (T0), but the differences were not statistically significant (p=0.120). Table 3.4. Longitudinal statistical comparisons of ISQs for MSIs that survived the entire study. T0 T1 T2 T3 T4 T5 T6 T7 T8 Mean 30.9 30.3 27.8 26.0 26.7 27.7 26.7 26.8 27.4 Std. Dev. 9.4 9.0 6.9 5.7 5.3 5.0 4.2 4.8 4.8 T0-1 T1-2 T2-3 T3-4 T4-5 T5-6 T6-7 T7-8 p-value 0.120 0.017* 0.006* 0.025* 0.008* 0.059 0.928 0.119 *significant at the !=0.05 level T0-1=placement to week one, T1-2=week one to week two, etc. 100 Figure 3.18: Mean ISQ values of MSIs that survived the entire study from placement (T0) through week eight (T8). Significant decreases in ISQ were demonstrated for T1-T2 and T2-T3. Significant increases in ISQ were demonstrated for T3-T4 and T4-T5. Discussion The high number of MSI failures (41%) that occurred were directly related to their placement in non-keratinized mucosa. Of the screws that were placed in non-keratinized mucosa only one survived the entire duration of the study (i.e. 90% of them failed). In contrast, none out of 12 MSIs placed in keratinized tissue failed. Success rates previously reported for MSIs range from less than 50% to over 95%.1-5 However, Most studies report success rates greater 80%.1,5 Chaddad et al. reported a 100% (11 out of 11 survived) success rate for MSIs placed in keratinized tissue;29 Cheng et al. also had a high success rate (92%, 101 103 out of 112 survived) for MSIs placed in keratinized tissue2; Lim et al. also showed a high success rate of 90.7% (224 out of 247) for MSIs placed in keratinized gingiva.30 Thus, the success rate of MSIs placed in kerati- nized tissue in the present study is in line with those reported elsewhere, emphasizing the importance of not placing MSIs in non-keratinized tissues. It has been previously suggested that the type of soft tissue into which MSIs are place is a risk factor for failure.1,2 The failures in this study strongly support de- creases in stability for MSIs placed in non-keratinized gingival tissue. The methodology of screwing and unscrew- ing the Smartpeg device to the head of the implant may have contributed to the high failure rate. All of the failures occurred while attempting to unscrew the Smartpeg, with the MSI unscrewing from the bone rather than the Smartpeg. Consequently, screws that would still be considered clinically usable due to lack of mobility, were considered failures, which could artificially inflate the failure rate. The greater decrease in ISQ experienced by MSIs placed in non-keratinized tissue indicates a greater loss of bone surrounding the implant, which is the ultimate cause of MSI failure. It has been suggested that a lack of keratinized tissue around MSIs leads to peri-implant inflammation and 102 eventual failure.2 With inflammation, catabolic processes, such as the resorption of bone traumatized during MSI insertion are favored, while anabolic processes, such as bone deposition and mineralization, are inhibited. This could lead to less bone surrounding an implant experiencing periimplant inflammation compared to an implant undergoing the healing process without excessive inflammation. MSIs that survive maintain a critical level of stability, while the stability of those that fail falls below threshold levels. Upon placement, the MSIs in the present study exhibited adequate primary stability. It was the loss of stability that determined whether or not MSIs would maintain adequate stability or fail. Our results show that the MSIs that failed exhibited an accelerated pattern of stability loss. During the first three weeks, they exhib- ited greater losses of stability than the MSIs that survived. While no previous studies have compared MSI stabil- ity changes during the first few weeks post placement, changes in stability have been used to identify dental implants at risk. Glauser et al. showed a larger decreases in stability among failed implants compared to those that survived.31 Friberg et al. and Huwiler et al. showed a similar pattern for dental implant failures.32,33 Sennerby and Meredith identify resonance frequency as a method to 103 predict failure of dental implants by evaluating changes in stability.26 Similarly, changes in stability could be used clinically to identify MSIs that are at the greatest risk of failing. To date, no other method has been shown to be an adequate predictor of MSI failure. However, this is an area that requires further research. The overall stability of any MSI is due to the combined effects of primary and secondary stability.15 While the primary and secondary stability curves make intuitive sense, it is impossible to separate them clinically when measuring stability. The best that can be done currently is to make inferences about the primary and secondary stability at any given point in time based on overall stability and an understanding of the physiological process of bone healing. The present study was designed to determine whether it was possible to identify when decreases in the primary stability of MSIs occur (i.e. the duration of time during which the overall stability curve decreases), and when secondary stability becomes more important than primary stability (i.e. when the overall stability curve starts to increase). Based on the results in the present study, the point of transition from primary to secondary stability appears to occur at approximately three weeks, 104 which compares closely to the point of transition identified for dental implants.22,23,33,34 (Figure 3.19 and 3.20). Figure 3.19: Stability of dental implants from placement (T0) through week eight (T8). Adapted from Huwiler et al.33 Figure 3.20: Mean ISQ values of MSIs that survived the entire study from placement (T0) through week eight (T8) divided by predominant stability type (P=primary or S=secondary). 105 Primary stability decreases immediately following MSI placement. The present study showed significant decreases in ISQ values during the first three weeks of the study. This supports the idea that primary stability is highest immediately after MSI placement, and then decreases over time, as previously demonstrated for dental implants. Bo- ronat et al. reported a decrease in ISQ during the first four weeks after dental implant placement in the maxilla and mandible;23 Ersanli et al., who measured stability at surgery, at three weeks, at six weeks and again at six months, reported significant decreases in ISQ values through three weeks;24 Balshi et al., who took monthly measures of ISQ showed statistically significant decreases in stability over the first month;22 Barewal et al. re- ported decreases in stability from placement to week three in bone that was considered type 2,3 or 4 (according to the index proposed by Lekholm and Zarb35).27 The decrease in primary stability of MSIs during the first three weeks can be explained by the physiological processes occurring around the implant. Within two hours of implant placement, erythrocytes, neutrophils, and macrophages coalesce in a fibrin network; osteoclasts and mesenchymal cells, which appear by day four, begin removal of bone damaged during MSI placement.19 This leads to the decreases in primary 106 stability observed in the present study and holds important implications for the management of MSIs. Strategies to re- duce trauma upon insertion or speed up the transition from primary to secondary stability should result in higher levels of MSI stability. Secondary stability, which is associated with healing and increases in total MSI stability, first becomes evident three weeks after miniscrew placement. The results indi- cate that secondary stability continues to increase through the fifth week, and then appears to level off. Boronat López et al. described an increase of stability for dental implants beginning the fourth week after placement.23 Stad- linger et al. reported increases in implant stability between the first and second months after dental implant placement; their ISQ values were lower after two months than at the time of placement.36 Barewal et al. also re- ported an increase in implant stability between week three and six. This increase of overall stability demonstrated between weeks three and six can be explained by the formation of bone surrounding a dental implant, which begins to occur at approximately three weeks post placement in dogs.34 Resonance frequency could be used to test whether surface treatments to MSIs, or other factors thought to accelerate secondary stability, enhance secondary stability. 107 Secondary stability is expected to continue to increase until complete healing around the MSI takes place. Stability in this study leveled off after week five and did not change significantly from week five to week eight. This pattern of healing does not agree with most of the dental implant literature, which reports increases in stability until much later.23,27,33 This difference can be ex- plained by circumstances surrounding the dogs. Rimadyl®, a non-steroidal anti-inflammatory (NSAID), was administered by the veterinarian to both dogs during this time period for pain control. It has been shown that NSAIDs may in- hibit bone formation and enhance bone resorption.37 This would explain the pattern of stability during this time period. The overall stability of MSIs eight weeks after placement was lower than the primary stability measured at placement. Even though the differences were not statisti- cally significant, the trend indicates a lower stability at eight weeks. According to Roberts, there are four stages of healing (activation, resorption, quiescence, formation) around dental implants, which take approximately 12 weeks in dogs.34 Since the present study lasted only eight weeks, approximately four weeks of bone formation remain, which 108 could account for the apparent lower stability observed at the eighth week. Whether or not the MSIs are placed with pilot holes appeared to have no appreciable effect on ISQ values. This suggests that, when placing MSIs in bone that is similar in density to the bone used in this study, pilot holes do not affect the MSI stability. These findings are at odds with the existing literature, which shows that pilot holes decrease insertion torque and pullout strength.38-40 It is possible that resonance frequency may not be sensitive enough to detect differences in stability between pilot holes and no pilot holes for MSIs. A more plausible expla- nation relates to the three factors that determine the resonance frequency of an implant, including its stiffness within the surrounding bone, the transducer that measures the vibration, and the length of the implant that extends out of the bone.26 Since the transducer and the length of the implant out of bone were held constant throughout the study, only the stiffness of the bone could explain differences in stability. Because the stiffness of the bone is a function of its physical composition, it might be expected to remain the same whether or not a pilot hole is placed. Since there were no differences in ISQ values after MSI placement, it does not appear that pilot holes enhance 109 the healing process. The results do not support the notion that pilot holes minimize trauma during MSI insertion, which should facilitate the healing process and improve stability. It may simply be that the placement of a pilot hole causes as much trauma to the bone as does the placement of a MSI with out a pilot hole. This may not be the case, however, for bone that is more dense than that used in the present study. Other methods may have to be used in order to enhance secondary stability, such as the surface treatment of the implant.41 Conclusions • Because the type of tissue has a significant effect on stability, it may be reasonable to assume that MSIs placed in non-keratinized tissue may be prone to higher failure rates. • MSIs that fail show significantly greater decreases in ISQ values over time than MSIs that remain stable. • Resonance frequency can be used to measure the changes in stability of MSIs over time. 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Oktenoğlu BT, Ferrara LA, Andalkar N, Ozer AF, Sarioğlu AC, Benzel EC. Effects of hole preparation on screw pullout resistance and insertional torque: a biomechanical study. J Neurosurg 2001;94:91-96. 40. Hung E. Varying Pilot Hole Size and Primary Stability. Saint Louis: Saint Louis University; 2009. 41. Strnad J, Urban K, Povysil C, Strnad Z. Secondary stability assessment of titanium implants with an alkalietched surface: a resonance frequency analysis study in beagle dogs. Int J Oral Maxillofac Implants 2008;23:502512. 115 VITA AUCTORIS Derid S. Ure was born on December 19, 1977 in Driggs, Idaho to Shane and Kaylin Ure. from 1996 through 1997. He attended Ricks College He interrupted his education to spend two years serving a religious mission for the Church of Jesus Christ of Latter-day Saints in Alabama from 1997 to 1999. Afterward, Derid resumed his studies at Ricks College where he received with an Associates of Arts in Economics in 2001. He received his Bachelor of Arts in Economics from Idaho State University in 2004. From 2004 to 2007, he attended the University of the Pacific Arthur A. Dugoni School of Dentistry in San Francisco, CA, where he received his Doctorate of Dental Surgery in 2007. It is anticipated that in January 2010 Derid will Graduate from Saint Louis University with a Master of Science degree in Dentistry with an emphasis in Orthodontics and will enter private practice in Texas. 116